Abstract The distal radial approach (dTRA) is increasingly recognized as a viable alternative to the conventional radial approach in coronary interventions. However, its utility in ST-elevation myocardial infarction (STEMI)—where rapid revascularization is critical—remains underexplored. To evaluate the feasibility and procedural characteristics of dTRA in STEMI patients undergoing primary percutaneous coronary intervention (PCI), using a prespecified subanalysis of the SPEEDY PCI study. Among 370 STEMI patients enrolled, 63 underwent PCI via dTRA and 307 via the conventional radial approach. A propensity score–matched analysis was performed using Killip class, GRACE score, and door-to-sheath time as covariates. After matching, the dTRA group had significantly shorter sheath-to-balloon (12.5 ± 11.5 vs. 19.7 ± 11.7 min, p  = 0.002) and door-to-balloon times (50.2 ± 25.9 vs. 62.3 ± 19.9 min, p  = 0.007). Procedural success and 30-day mortality rates were comparable between groups. dTRA appears feasible and safe for STEMI patients in high-volume centers. While shorter time metrics were observed, these may reflect institutional practices and operator experience rather than the access site alone.

BACKGROUND: Preprocedural screening using transesophageal echocardiography (TEE) and computed tomography (CT) is widely performed in patients undergoing left atrial appendage (LAA) closure (LAAC). However, established methods for accurately predicting procedural device success (DS) remain unclear. AIMS: This study aimed to evaluate whether a novel preprocedural CT-based assessment focusing on the landing zone and presence of an internal septum could improve DS prediction. METHODS: We analyzed 560 patients from a Japanese multicenter registry who underwent LAAC with Watchman FLX (Boston Scientific, USA). Preprocedural CT multiplanar reconstruction measured the diameter of the LAA landing zone (Dland), LAA length (L), and major lobe ostium diameter (Dlobe), if present. Based on these measurements, a ratio calculation (Rcal), defined as L/(Dland-Dlobe), was used to predict DS. The predictive performance of this ratio was evaluated using receiver operating characteristic (ROC) curve analysis and compared with that of conventional CT- and TEE-derived depth-to-ostium ratios. RESULTS: DS was achieved in 95.5% (535/560) of patients. The mean Rcal was significantly lower in the failure group than in the success group (0.66 ± 0.25 vs. 1.00 ± 0.28; p < 0.001). Rcal predicted DS with an area under the ROC curve (AUC) of 0.872 (p < 0.001). An optimal Rcal cutoff of 0.77 demonstrated 80.0% sensitivity and 83.4% specificity. Rcal showed superior predictive performance compared with CT depth/ostium ratio (AUC: 0.552) and TEE depth/ostium ratio (AUC: 0.456). CONCLUSIONS: The novel CT-derived metric, Rcal, which accounts for LAA landing zone dimensions and internal septa, predicts the DS of Watchman FLX. Rcal may improve pre-LAAC patient selection and procedural planning.

BACKGROUND: Spontaneous echo contrast (SEC) with atrial fibrillation (AF) is known to increase stroke risk. However, the effect of SEC grades on outcomes after left atrial appendage closure (LAAC) remains unclear. OBJECTIVES: This study aimed to evaluate the impact of SEC grades on clinical outcomes after LAAC. METHODS: A total of 1,276 consecutive patients undergoing LAAC were analyzed. They were classified into SEC 0+, SEC 1/2+, and SEC 3/4+ groups based on preprocedural transesophageal echocardiography. Clinical outcomes were compared among the groups. RESULTS: There were 595 (46.6%), 509 (39.9%), and 172 (13.5%) patients in the SEC 0+, SEC 1/2+, and SEC 3/4+ groups, respectively. The SEC 3/4+ group (11.5%) had a higher ischemic stroke/transient ischemic attack/systemic embolism incidence than the SEC 0+ (4.4%; P = 0.009) and SEC 1/2+ (5.4%; P = 0.047) groups; SEC grade, however, was not a significant predictor in multivariate analysis. Compared with the SEC 0+ group (2.8%), both the SEC 1/2+ (8.4%; P < 0.001) and SEC 3/4+ (12.4%; P < 0.001) groups were associated with a higher risk of device-related thrombus (DRT). When SEC grade and AF type were combined for assessment, SEC 3/4+ with nonparoxysmal AF was associated with both thromboembolic events (adjusted HR: 2.52; 95% CI: 1.22-5.20; P = 0.013) and DRT (adjusted HR: 2.89; 95% CI: 1.50-5.60; P = 0.003). CONCLUSIONS: Patients with greater SEC grade displayed a higher incidence of thromboembolic events and DRT, and combined SEC grade and AF type independently predicted these events. Further research is needed regarding optimal treatment strategy in patients with severe SEC.

BACKGROUND: One-year clinical and hemodynamic outcomes after transcatheter aortic valve replacement (TAVR) using the latest generation balloon-expandable valve (BEV) and self-expandable valve (SEV) is not well understood. This study is aimed to compare 1-year morality and hemodynamics between the latest generation BEV and SEV after TAVR. METHODS: We retrospectively analyzed 1393 patients undergoing TAVR using BEV (63.7%) (SAPIEN3 Ultra RESILIA) and SEV (36.3%) (Evolut FX). The incidence of all-cause mortality and bioprosthetic valve dysfunction (BVD) over 1-year were compared between BEV and SEV in both overall and propensity score (PS) matched cohort. RESULTS: During 1-year follow-up, the incidence of all-cause mortality was comparable between BEV and SEV in the overall (10.8% vs. 8.0%, log-rank p = 0.30) and PS matched cohort (11.0% vs. 8.9%, log-rank p = 0.40). The incidence of BVD through 1-year was also comparable between BEV and SEV in the overall (6.2% vs. 6.9%, p = 0.59) and PS matched cohort (6.7% vs. 8.2%, p = 0.55). Of BVD component, post-procedural mean pressure gradient more than 20mmH was higher in BEV, while para-valvular leakage more than moderate was higher in SEV. There was non-linear relationship between annulus size and BVD, in which TAVR with BEV had higher BVD in a small annulus, while SEV had higher BVD in a large annulus. CONCLUSIONS: In TAVR using the latest generation valves, incidences of mortality and valve performance during 1-year were comparable between BEV and SEV. Whereas, the impact of annulus size on the difference of valve hemodynamics between BEV and SEV is still observed.

BACKGROUND AND AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) is an established therapy for functional mitral regurgitation (FMR) and reduced left ventricular ejection fraction (LVEF). Although guideline-directed medical therapy (GDMT) is ideally optimized before M-TEER, this procedure may facilitate early post-procedural GDMT changes. However, the clinical impact of early in-hospital GDMT modifications remains unclear. METHODS: We analyzed 1,638 patients with FMR and LVEF <50% enrolled in a multicenter Japanese registry. The patients were stratified according to the number of GDMT classes prescribed at discharge (single [n=183]; double [n=505]; triple [n=630]; quadruple [n=320]). Changes from before M-TEER to discharge were categorized as increased (n=271), unchanged (n=1,219), or decreased (n=148). Associations between GDMT patterns and subsequent outcomes were evaluated. The primary endpoint was a composite of all-cause mortality and heart failure rehospitalization at one year. RESULTS: Primary endpoints were achieved in 357 patients (22%). Event rates decreased across groups (single, 32%; double, 24%; triple, 21%; quadruple, 14%; P<0.001). After adjusting for confounders, a greater number of GDMT classes at discharge independently predicted better prognosis. (hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.73-0.95), whereas pre-M-TEER GDMT was not significant. Compared with decreased GDMT, an unchanged status was not associated with improved outcomes, while an increased status significantly improved prognosis (HR 0.62, 95% CI 0.39-0.99). CONCLUSION: In patients with FMR and LVEF <50%, a higher number of GDMT classes at discharge and in-hospital uptitration of the GDMT class were associated with better outcomes, suggesting that early postprocedural GDMT optimization warrants further investigation.

AIMS: Residual mitral regurgitation (MR) after mitral transcatheter edge-to-edge repair (M-TEER) is associated with adverse prognosis. However, the long-term clinical impact of MR persistence or progression has not been well stratified. We aimed to evaluate the proportion, clinical benefits, and prognostic value of maintaining mild MR one year after M-TEER. METHODS AND RESULTS: This multicenter registry-based analysis included 1,865 patients who achieved mild MR at discharge following M-TEER. At one year, patients were classified as having stable MR (≤ mild) or worsening MR (≥ moderate). The frequency of left atrial (LA) and left ventricular (LV) reverse remodeling and tricuspid regurgitation (TR) improvement were assessed from baseline to one year. Clinical endpoints-including all-cause mortality and heart failure hospitalization-were evaluated beyond one year after M-TEER up to two years. Worsening MR occurred in 28.4% of patients. Compared with the worsening MR group, the stable MR group demonstrated significantly more frequent LA and LV reverse remodeling (38.4% vs. 28.1%, and 44.7% vs. 31.1%, respectively; both p<0.001). Improvement in TR (≥ grade 1) was also more prevalent in the stable MR group (32.4% vs. 20.6%, p<0.001). Worsening MR was independently associated with increased risk of adverse clinical outcomes (hazard ratio: 2.02; 95% confidence interval: 1.26-3.23; p=0.003). CONCLUSIONS: Maintaining MR within mild at one-year post-M-TEER is associated with favorable cardiac reverse remodeling and improved clinical prognosis. These findings underscore the importance of long-term MR surveillance and its implications for outcome optimization following M-TEER.

BACKGROUND: The clinical significance of mild paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR) remains uncertain. OBJECTIVES: The aim of this study was to evaluate the impact of mild PVR on long-term clinical outcomes and bioprosthetic valve failure (BVF) following TAVR. METHODS: A total of 5,068 patients from the OCEAN-TAVI (Optimized Catheter Valvular Intervention-Transcatheter Aortic Valve Implantation; UMIN000020423) registry who underwent TAVR and had no or trace or mild PVR at discharge were analyzed. Patients were stratified according to PVR severity and followed for up to 9 years. The primary outcomes were all-cause mortality and BVF, defined according to Valve Academic Research Consortium 3 criteria. RESULTS: Median follow-up duration was 4.7 years (Q1-Q3: 2.9-6.0 years). Mild PVR was observed in 1,601 patients (31.6%). At 9-year follow-up, Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of all-cause mortality (75.9% [95% CI: 71.3%-80.2%] vs 72.2% [95% CI: 68.1%-76.3%]; log-rank P = 0.014) and BVF (20.7% [95% CI: 12.8%-32.5%] vs 17.3% [95% CI: 11.0%-26.6%]; P = 0.029) in patients with mild PVR than in those with no or trace PVR. Fine-Gray analysis confirmed mild PVR as an independent predictor of BVF (subdistribution HR [sHR]: 1.48; 95% CI: 1.07-2.04; P = 0.018), and Cox regression showed a significant association with all-cause mortality (HR: 1.11; 95% CI: 1.02-1.21; P = 0.014). The risk for BVF was especially elevated in patients receiving balloon-expandable valves (sHR: 1.46; 95% CI: 1.02-2.08; P = 0.038), those undergoing nontransfemoral TAVR (sHR: 5.58; 95% CI: 1.57-19.9; P = 0.0086), and those with impaired renal function (estimated glomerular filtration rate < 30 mL/min/1.73 m2; sHR: 3.86; 95% CI: 1.30-11.5; P = 0.015). Baseline mild PVR was independently associated with an increased risk for progression to moderate or greater PVR (HR: 3.74; 95% CI: 2.84-4.92; P < 0.001). CONCLUSIONS: Mild PVR after TAVR is associated with a significantly increased risk for BVF and all-cause mortality, highlighting the importance of optimizing valve deployment and monitoring patients with even mild PVR.

BACKGROUND: The management of coronary artery disease in patients with severe aortic stenosis is controversial, with no consensus on optimal revascularization strategies. The validity of using fractional flow reserve to assess ischaemia in this population is debated. Conflicting results have arisen regarding the impact of transcatheter aortic valve implantation on fractional flow reserve values. We present the case of a patient with severe aortic stenosis and intermediate left anterior descending artery stenosis, in whom the fractional flow reserve and the index of microcirculatory resistance suggested the presence of coronary microvascular dysfunction prior to transcatheter aortic valve implantation. However, after valve replacement, the fractional flow reserve and the index of microcirculatory resistance indicated physiologically significant ischaemia, prompting intervention. CASE SUMMARY: An 82-year-old woman presented with paradoxical low-flow, low-gradient severe aortic stenosis and intermediate left anterior descending artery stenosis. The fractional flow reserve was borderline, and the index of microcirculatory resistance was elevated before transcatheter aortic valve implantation, indicating the presence of coronary microvascular dysfunction. Six months after valve replacement, the fractional flow reserve declined to 0.64 with an improved index of microcirculatory resistance, prompting a successful percutaneous coronary intervention. Subsequent cardiac magnetic resonance imaging revealed reverse remodelling with a reduced left ventricular mass. DISCUSSION: This case illustrates that transcatheter aortic valve implantation may unmask coronary ischaemia by restoring microvascular vasodilatory capacity in patients with coronary microvascular dysfunction. It also highlights the importance of reassessing coronary physiology in selected patients following transcatheter aortic valve implantation.

The changes in tricuspid regurgitation (TR) following transcatheter atrial septal defect (ASD) closure, in relation to preprocedural cardiac rhythms, remain unknown. This study aimed to assess sequential changes in TR after ASD closure based on cardiac rhythms. Patients were categorized as sinus rhythm (SR group, n = 89), SR after catheter ablation for atrial fibrillation (ABL group, n = 14), and permanent atrial fibrillation (AF group, n = 12). Echocardiography was performed at baseline, 1 day, 1 month, and 12 months after the procedure. There were significant differences in age (54.5 ± 17.5 years vs 63.9 ± 12.6 years vs 74.3 ± 8.4 years; p < 0.01) and prevalence of moderate ≥ TR at baseline (44.9% vs 78.6% vs 91.7%; p < 0.01) in the SR, ABL, and AF groups, respectively. The SR group showed significant improvement in TR as early as 1-day postclosure, which persisted at 12 months, whereas the ABL and AF groups exhibited no significant improvements in TR at any point postprocedure. Independent predictors of residual moderate ≥ TR at 12 months included being in the ABL or AF groups and having a higher right atrial volume index (RAVI) at baseline. In conclusion, persistent TR may remain after ASD closure, even for patients who achieve SR postablation and those with permanent AF. This persistence may reflect baseline atrial remodeling, as indicated by larger RAVI, beyond volume unloading after ASD closure. These findings highlight the importance of timely therapeutic interventions and careful monitoring for residual TR following ASD closure, especially in patients with a history of AF.

BACKGROUND: Transcatheter edge-to-edge repair of the mitral valve (M-TEER) has demonstrated promising outcomes for patients with mitral regurgitation who are unsuitable for surgical intervention. However, the clinical implications of M-TEER in patients requiring mechanical circulatory support (MCS) for unstable hemodynamics remains unclear. This study aimed to evaluate the outcomes of MCS-assisted M-TEER in critically ill patients. METHODS: Consecutive patients who underwent M-TEER for significant mitral regurgitation were identified from the Japanese multicenter OCEAN-Mitral (Optimized Catheter Valvular Intervention-Mitral) registry. All-cause death was compared between the cohort undergoing MCS-assisted M-TEER and a virtual control group receiving MCS alone without undergoing M-TEER, estimated using the Seattle Heart Failure Model. Additionally, logistic regression analysis was conducted to identify factors associated with in-hospital death following MCS-assisted M-TEER. RESULTS: A total of 3764 patients were included in the analysis (mean age, 81 years; 54.9% men; 70.1% with secondary mitral regurgitation), of whom 105 underwent MCS-assisted M-TEER. Procedure success exceeded 95%, irrespective of MCS use. The 1-year mortality rate in the MCS-assisted M-TEER group was lower than the estimated mortality rate in the virtual control group (43.2% versus 69.5%). Factors associated with in-hospital death included frailty, inflammation, and hypoalbuminemia. In a landmark analysis starting from discharge date, there was no statistically significant difference in cardiovascular death or heart failure hospitalization between the groups with or without the use of MCS (hazard ratio, 1.45 [95% CI, 0.93-2.26]; P=0.10). CONCLUSIONS: MCS-assisted M-TEER appears to be a viable and effective therapeutic strategy for carefully selected patients with significant mitral regurgitation and unstable hemodynamics. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN-ID: UMIN000023653.

BACKGROUND: Pulmonary diseases (PD) are frequently associated with impaired cardiac function and the presence of mitral and tricuspid regurgitation (MR and TR). OBJECTIVES: The study aimed to clarify the impact of PD on clinical outcomes following mitral transcatheter edge-to-edge repair (M-TEER). METHODS: Of the 3,764 patients who underwent M-TEER, 3,666 were included in the analysis and stratified according to the absence or presence of PD before the procedure. The primary endpoint was all-cause mortality, evaluated using Kaplan-Meier analysis. Cardiovascular and non-cardiovascular mortality and HFH (HFH) were also assessed during a 4-year follow-up. Moreover, the prognostic impact of TR improvement after M-TEER was evaluated in patients with and without PD. RESULTS: Of the 3,666 patients, 580 (15.8%) had PD, included fewer women, and exhibited greater frailty compared with those without PD. Within a median follow-up of 432 [314-826] days, all-cause mortality did not differ significantly between patients with PD and those without (150 [25.9%] vs. 682 [22.1%], Log rank P = 0.331). No significant differences were observed in the incidence of cardiovascular mortality, non-cardiovascular mortality, and HFH between the two groups. When stratified by PD status, residual significant TR after M-TEER was significantly associated with HFH both in patients with PD and without PD. CONCLUSIONS: The intermediate-term prognosis after M-TEER was comparable between patients with and without PD. In patients with PD, MR was effectively reduced through minimally invasive M-TEER. However, appropriate management of TR after MTEER may be required to improve outcomes in this population. CLINICAL TRIALS: OCEAN-Mitral registry (UMIN-ID: UMIN000023653).

BACKGROUND: Limited evidence has been available on the long-term prognosis and valve durability of balloon-expandable transcatheter heart valve (BE-THV) and self-expandable transcatheter heart valve (SE-THV) in patients with large aortic annulus (LAA). OBJECTIVES: To compare the long-term outcomes between the BE-THV and SE-THV. METHODS: We retrospectively analyzed 1054 patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) for tricuspid aortic valve stenosis with LAA, defined as an annulus area > 430 mm2, using either a BE-THV (SAPIEN 3, Edwards Life Sciences) or SE-THV (Evolut R/PRO, Medtronic). The 7-year cumulative incidences of all-cause mortality and bioprosthetic valve failure (BVF) were evaluated in the overall cohort and the propensity score (PS)-matched cohort. RESULTS: Among the 1054 patients with LAA, 829 (78.7 %) received a BE-THV. The PS-matched population resulted in 218 pairs. The cumulative incidence of all-cause mortality 7 years after TAVI was comparable between the BE-THV and SE-THV groups in the overall cohort (58.6 % vs. 67.6 %, log-rank P = 0.848) and the PS-matched cohort (53.2 % vs. 69.9 %, log-rank P = 0.173). In the overall cohort, the BE-THV group demonstrated a lower exposure-adjusted BVF rate as compared with the SE-THV, although the difference was not significant (6.1 vs. 9.6 events per 1000 patient-years, P = 0.258). This trend became pronounced after PS matching (3.3 vs. 9.9 events per 1000 patient-years, P = 0.017), which was also confirmed by Gray's test (P = 0.032). CONCLUSIONS: In the current analysis focusing on patients with LAA, the BE-THV and SE-THV groups had a comparable long-term prognosis, but the BE-THV group had a lower BVF rate than did the SE-THV group. CLINICAL TRIAL REGISTRATION: UMIN000020423.

BACKGROUND: The interplay between atrial fibrillation (AF) and tricuspid regurgitation (TR) has been recognized. However, it is not simple and has not been fully investigated. OBJECTIVES: The aim of this study was to examine the association among AF, TR, and outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER). METHODS: Patients were divided into 4 groups according to the presence of AF and postprocedural significant TR (moderate or greater): no AF and no TR, no AF with significant TR, AF and no TR, and AF with significant TR. The primary outcome was cardiovascular death or heart failure (HF) hospitalization. Right heart structure and function were also evaluated according to AF and TR status. RESULTS: The numbers of patients in each group were 1,184 (no AF and no TR), 229 (no AF with significant TR), 1,423 (AF and no TR), and 830 (AF with significant TR). AF was associated with a higher prevalence of significant TR at baseline and more frequent TR progression and less common improvement during follow-up. Both AF and TR appeared to be independently associated with right-ventricular remodeling and dysfunction, with distinct patterns observed according to MR and TR pathologies. TR grade moderate or greater after M-TEER was associated with a higher adjusted risk for cardiovascular death or HF hospitalization, especially in patients with AF (Pinteraction = 0.02). CONCLUSIONS: Patients with AF, compared with those without AF, experienced greater incidence and progression and less common improvement of TR after M-TEER. In addition, both AF and TR appeared to be independently associated with worse right ventricular status and an increased risk for HF outcomes.

BACKGROUND: Associations between optimal low-density lipoprotein cholesterol (LDL-C) level and changes in coronary flow and plaque characteristics are unclear. Therefore, we examined the effect of LDL-C lowering changes lipid-rich coronary plaques and flow using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) and quantitative flow ratio (QFR) in non-culprit vessels of patients with acute coronary syndrome (ACS). METHODS: We prospectively examined 72 patients with ACS who underwent NIRS-IVUS for intermediate stenosis in non-culprit vessels at baseline and at follow-up. According to patients' LDL-C levels at follow-up, they were classified into two groups. Patients with LDL-C levels < 55 mg/dL were categorized into the very low LDL-C group (VL group), while those with LDL-C levels ≥ 55 mg/dL were categorized into the low LDL-C group (L group). Changes in the lesion lipid core burden index (LCBI) and maximum 4-mm lipid core burden index (maxLCBI4mm) were assessed using NIRS-IVUS. Coronary flow was assessed using the QFR. The differences (Δ) between each value at follow-up and at baseline were determined. RESULTS: The median LDL-C level at follow-up was 48 (42-53) mg/dL in the VL group and 64 (60-68) mg/dL in the L group. There was a strong correlation between reduction of maxLCBI4mm and improvement of QFR (R2 = 0.58). The VL group showed a significant decrease in maxLCBI4mm along with improvement in QFR value compared with the L group (P = 0.003; P = 0.008, respectively). The proportion of plaques with a maxLCBI4mm ≥ 400 (18.1% vs. 53.6%, P = 0.002) and the lesion LCBI (35.5(8.25-74) vs. 88.5(42.8-132), P = 0.03) at follow-up was lower in the VL group than in the L group. Plaques with a maxLCBI4mm ≥ 400 at baseline changed more frequently to a maxLCBI4mm < 400 at follow-up in the VL group than in the L group (36% vs. 4%, P = 0.001). CONCLUSION: Aggressive LDL-C-lowering therapy for non-culprit intermediate stenosis in ACS appears to promote plaque stabilization and improve coronary flow.

BACKGROUND: Evidence regarding the long-term outcomes and durability of balloon-expandable transcatheter heart valves (BE-THVs) after transcatheter aortic valve implantation (TAVI) is still scarce. AIMS: This study evaluates these outcomes and further examines their association with the annular size in patients. METHODS: A total of 2,699 patients who had undergone TAVI with a BE-THV at least 5 years prior to our study were analysed. A small aortic annulus (SAA) was defined as an area ≤430 mm2; any larger annuli were labelled large aortic annuli (LAA). The primary endpoints were the incidence of all-cause mortality and bioprosthetic valve failure (BVF) between the SAA and LAA groups. As a subanalysis, the primary endpoints were examined in relation to postprocedural mean pressure gradient (mPG) ≥20 mmHg, severe prosthesis-patient mismatch (PPM), and sex differences, comparing SAA and LAA each time. RESULTS: Overall, 66.4% (n=1,793) of patients were categorised into the SAA group. At 7 years after TAVI, the cumulative all-cause mortality showed differences between the SAA and LAA groups (55.2% vs 58.6%), while BVF assessed by Gray's test was similar between the groups (3.3% vs 2.7%). The Cox multivariable analysis revealed no association between SAA and worse prognosis (hazard ratio 1.07, 95% confidence interval: 0.85-1.36; p=0.56). There were no significant differences in mortality or BVF regarding an mPG ≥20 mmHg, severe PPM, or sex between the SAA and LAA groups (allp>0.05). CONCLUSIONS: Annular size differences were not found to influence long-term outcomes or valve durability following TAVI with a BE-THV, suggesting that other factors warrant further investigation.

BACKGROUND: Although reducing mitral regurgitation (MR) after mitral transcatheter edge-to-edge repair (M-TEER) improves outcomes, the impact of increased transmitral mean pressure gradient (TMPG) remains controversial. OBJECTIVES: This study aimed to evaluate the clinical significance of MR reduction and TMPG elevation in patients with functional mitral regurgitation (FMR) after M-TEER. METHODS: A total of 2,360 FMR patients were evaluated using postdischarge echocardiography after M-TEER. The relationship between TMPG and outcomes was assessed using spline analysis and group-based comparisons. Based on residual MR severity and TMPG, patients were categorized into 5 groups to assess the prognostic impact of postprocedural hemodynamics: MR ≤ mild and TMPG <5 mm Hg (n = 1,702), MR ≤ mild and TMPG ≥5 to <10 mm Hg (n = 164), moderate MR and TMPG <5 mm Hg (n = 361), moderate MR and TMPG ≥5 to <10 mm Hg (n = 71), and MR > moderate or TMPG 10 mm Hg (n = 62). The primary endpoint was all-cause death or heart failure hospitalization. RESULTS: The 2-year primary endpoint event rates increased progressively with higher TMPG, from 25.0% at 1 mm Hg to 47.0% at 6 mm Hg. In multivariable analysis, TMPG per 1 mm Hg increment was independently associated with the primary endpoint (HR: 1.10; 95% CI: 1.02-1.17; P = 0.008). Using MR ≤ mild as the reference, moderate MR was not linked to higher risk, whereas MR > moderate remained a significant predictor of primary endpoint. The patients with MR ≤ mild and TMPG <5 mm Hg had the lowest incidence of the primary endpoint among the 5 groups (28.4%, 39.0%, 33.0%, 43.7%, 48.4%; P < 0.001). However, event risk was not significantly different between patients with moderate MR and TMPG <5 mm Hg and those with MR ≤ mild and TMPG <5 mm Hg (HR: 1.13; 95% CI: 0.92-1.41; P = 0.24). Failure to achieve MR ≤ mild and TMPG <5 mm Hg was associated with larger left atrial volume index, greater effective regurgitation orifice area, elevated baseline TMPG, and old-generation G2 device use. CONCLUSIONS: In patients with FMR, elevated TMPG was consistently associated with higher risks of the primary endpoint. Mild or moderate residual MR with low TMPG was associated with more favorable prognosis, suggesting that balancing MR reduction and TMPG may help refine risk stratification after M-TEER. (Japanese Registry study of valvular heart diseases treatment and prognosis; UMIN000023653).

AIMS: In patients with ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (M-TEER), the prognostic significance of the ratio between mitral regurgitant volume and left atrial volume (LAV) remains unclear. This ratio may reflect the proportional or disproportionate burden of regurgitation on the left atrium. To address this gap, we aimed to investigate the association between the regurgitant volume (RVol)/LAV ratio and clinical outcomes in patients with VFMR, using data from a multicentre prospective registry. METHODS AND RESULTS: We calculated the RVol/LAV ratio from baseline transthoracic echocardiograms. The median value of the RVol/LAV ratio was 0.40. A total of 1830 patients who underwent M-TEER were allocated into two groups: the low RVol/LAV (RVol/LAV ratio <0.40) and high RVol/LAV (RVol/LAV ratio ≥0.40) groups. The primary endpoint was heart failure hospitalization.Eight hundred eighty-eight and 942 patients were included into the low RVol/LAV ratio and high RVol/LAV ratio groups, respectively. The median follow-up period was 508 days. At three years after repair, 215 (37.6%) and 187 (32.1%) patients in the low RVol/LAV and high RVol/LAV groups, respectively, were hospitalized for heart failure. The patients in the low RVol/LAV group demonstrated a significantly higher risk of heart failure hospitalization than did those in the high RVol/LAV group (hazards ratio, 1.25; 95%confidence interval, 1.03-1.52; p = 0.022). Furthermore, using multivariable Cox regression analysis, the low RVol/LAV was an independent predictor of the primary endpoint. CONCLUSIONS: The RVol/LAV ratio might serve as a valuable metric for improving risk stratification in patients with VFMR.

BACKGROUND: Target lesion calcification is known to influence the percutaneous coronary intervention (PCI) outcomes. This study aimed to assess the impact of calcium fractures after balloon angioplasty on the PCI results as well as the long-term clinical outcomes. METHODS: We formed a prospective, multicenter registry that enrolled 268 patients who underwent PCI to lesions with moderate to severe calcification. Balloon dilatation and subsequent drug eluting stent implantation were performed with optical coherence tomography (OCT) guidance in every case. Serial OCT images just before and after balloon angioplasty, and after stent implantation were analyzed at 1-mm intervals by an independent core laboratory. The primary endpoint was the relationship between calcium fracture after balloon angioplasty and stent expansion. The secondary endpoint was target vessel failure (TVF) at 1 year, defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. RESULTS: A total of 242 patients were analyzed. Of these, OCT analysis was performed in 147 patients with a complete OCT data set. Calcium fractures were observed in 28 patients (19%) at the minimal lumen area site. The percent stent expansion was greater in lesions with calcium fracture than those without (99 ± 26% vs. 91 ± 18%, p = 0.039). In 229 patients who underwent clinical follow-up at 1 year, TVF occurred in 23 patients (10.0%). CONCLUSION: The OCT-guided PCI strategy demonstrated acceptable acute and 1-year clinical outcomes. The presence of calcium fractures after balloon angioplasty may have a potential impact on acute results after DES implantation in calcified lesions.

The KCB01 (KIZASHI™) is a novel cutting balloon catheter with blades integrally formed with the balloon. It is designed to overcome the drawbacks of conventional cutting balloons in terms of lesion delivery, crossability and procedural complications while maintaining the same dilation capacity. To evaluate the efficacy and safety of the KCB01, a prospective, open-label, single-arm study was conducted at nine sites in Japan on percutaneous coronary intervention-eligible patients with stenotic lesions that exhibited residual indentation even after conventional balloon dilation at nominal pressure. Seventy-six patients were enrolled between November 2022 and June 2023, and 73 eligible patients were included in the primary analysis. The mean age was 73.5 ± 7.4 years, and 79.5% of the patients were male. The target lesion characteristics included bifurcation lesions (42.5%), in-stent restenosis lesions (20.5%), and severely calcified lesions (54.8%). The primary endpoint was procedural success, defined as the KCB01 crossing the target lesion, no residual indentation, and < 50% residual stenosis rate after KCB01 dilation (assessed using quantitative coronary angiography). The angiographic images obtained during the procedure were evaluated in a core laboratory. The procedural success rate was 87.7% (95% confidence interval [CI]: 77.9-94.2), with the lower limit of the 95% CI (77.9%) exceeding the performance goal of 76.5%. Clinical success rate was achieved in 94.5% of cases (95% CI: 86.6-98.5%), with no major adverse cardiac events reported until discharge. Furthermore, no device deficiencies related to the KCB01 were observed. These results suggest the safety and efficacy of the KCB01.

BACKGROUND: Given the relatively high morbidity and death associated with transcatheter edge-to-edge repair for secondary mitral regurgitation, the development of optimal risk stratification models is imperative. The J-MACS (Japanese Registry for Mechanically Assisted Circulatory Support) score is a recently developed tool designed to stratify risk in patients with advanced heart failure undergoing durable left ventricular assist device implantation. METHODS: Data were obtained from the OCEAN-Mitral (Optimized Catheter Valvular Intervention-Mitral) registry on patients with secondary mitral regurgitation and left ventricular ejection fraction <50% who underwent transcatheter edge-to-edge repair. A newly innovated modified J-MACS score, incorporating age, history of cardiac surgery, serum creatinine levels, and postprocedural moderate or greater tricuspid regurgitation, was calculated. Its prognostic significance regarding the primary outcome, comprising all-cause death and heart failure-related hospitalizations, was assessed. RESULTS: A total of 2006 patients (median age, 77 years; 63% men) were included in the study. The median modified J-MACS score was 13.7 (interquartile range, 12.0-16.2). Based on statistically calculated optimal cutoff values of 11.4 and 14.0, patients were stratified into 3 risk categories: low, moderate, and high. The 2-year cumulative incidence of the primary outcome differed significantly among these groups (26%, 37%, and 51%, respectively; P<0.001). Risk group classification remained independently associated with the primary outcome, with an adjusted hazard ratio of 1.42 (95% CI, 1.13-1.71; P<0.001) for the intermediate risk versus low risk and 2.27 (95% CI, 1.67-2.96; P<0.001) for the high risk versus low risk. CONCLUSIONS: The modified J-MACS score demonstrated an independent association with all-cause death and heart failure-related hospitalization following transcatheter edge-to-edge repair in patients with significant mitral regurgitation and systolic heart failure. REGISTRATION: URL: https://upload.umin.ac.jp; Unique Identifier: UMIN000023653.

BACKGROUND: Mitral valve transcatheter edge-to-edge repair (M-TEER) is an established effective treatment for patients with mitral regurgitation. The Geriatric Nutritional Risk Index (GNRI) is a well-known nutritional marker that predicts mortality risk; however, no reports clarify the clinical impact of GNRI reversibility after M-TEER. OBJECTIVES: The purpose of this study was to investigate the association between GNRI reversibility and clinical outcomes after M-TEER and identify factors predicting early GNRI improvement. METHODS: Data from 1,909 patients enrolled in the Japanese multicenter registry whose GNRI values were measured before and 1 month after undergoing M-TEER were retrospectively reviewed. Changes in GNRI (Δ-GNRI) were calculated and divided into two groups, namely improved GNRI (Δ-GNRI >0) and worsening GNRI (Δ-GNRI ≤0) groups. Multivariate logistic regression analysis was performed to explore factors associated with improvement in Δ-GNRI. Cox regression analysis was used to examine associations with long-term all-cause mortality or composite outcome. RESULTS: Among the 1,909 patients, GNRI improved in 54.8% of patients. The median follow-up period was 1.3 years; 433 patients died during the follow-up period. The Δ-GNRI improvement was significantly associated with younger age, achievement of acute procedural success, lower high-sensitivity C-reactive protein, and preprocedural high GNRI value (all P < 0.05), and was significantly associated with a lower risk of death and composite outcome. CONCLUSIONS: The Δ-GNRI is a useful predictor of long-term prognosis, with reversibility observed in half of patients after M-TEER. Improvement in Δ-GNRI is associated with acute procedural success, underscoring the importance of assessing the potential for procedural success before M-TEER.

BACKGROUND: The association of outcomes with initial clip selection has not been investigated in patients undergoing transcatheter edge-to-edge repair with the MitraClip G4. METHODS: We analyzed 2257 patients receiving the MitraClip G4 according to the initial clip type: short (NT/NTW) versus long (XT/XTW) and narrow (NT/XT) versus wide (NTW/XTW). We performed a propensity-matched analysis of baseline anatomical features in patients with primary and secondary mitral regurgitation (MR). RESULTS: The proportions of the initial clip types were as follows: NT, 18.9%; NTW, 41.7%; XT, 5.1%; and XTW, 34.3%. The proportions of the MR severity ≤1+ at discharge and 1 year were not significantly different among the 4 clip types. The incidence of death or heart failure hospitalization was not significantly different between the initial long and short clip groups and between the initial wide and narrow clip groups. After propensity matching, in patients with primary MR, long clips were significantly associated with a greater MR reduction (2.87±0.89 versus 2.62±0.99, P=0.04) and a higher proportion of the MR severity ≤1+ at 1 year (68.2% versus 48.6%, P=0.04) than short clips. In patients with secondary MR, long or wide clips had a similar MR severity at discharge and 1 year as short or narrow clips. CONCLUSIONS: Residual MR severity and outcomes were not different regardless of the initial clip type, indicating the optimal clip selection in the real-world settings with the MitraClip G4. In patients with primary MR, greater and more durable MR reduction may be expected by using the initial long clips. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN-ID: UMIN000023653.

BACKGROUND: Coronary microvascular dysfunction (CMD) has recently been associated with adverse cardiovascular events in patients with heart failure. We investigated the relationship between late gadolinium enhancement (LGE) and CMD, as well as the prognostic value of CMD in predicting long-term prognosis in patients with dilated cardiomyopathy (DCM). METHODS: Patients with DCM who underwent both cardiac magnetic resonance imaging and coronary angiography were consecutively enrolled. CMD was evaluated using the angiography-derived index of microcirculatory resistance (angio-IMR). The primary endpoint was composite endpoints of all-cause mortality or heart failure hospitalization within 3 years. RESULTS: Among 108 patients (median age, 64 years; women, 27 %), 18 % (19 patients) experienced composite endpoints. The median angio-IMR was 45 U, and LGE was identified in 23 %. Angio-IMR was significantly higher in patients with LGE than in those without LGE. When patients were stratified based on the combined presence of LGE and angio-IMR, significant differences in composite endpoints were observed among the three groups (LGE absence and low angio-IMR: 4.3 % vs. LGE presence or high angio-IMR: 22.2 % vs. LGE presence and high angio-IMR: 41.2 %, log-rank test p < 0.01). In multivariable Cox proportional hazards model for composite endpoints, LGE presence and angio-IMR >45 U was an independent predictor: hazards ratio 12.20, 95 % confidence interval 2.40-62.10, p = 0.001. CONCLUSION: CMD evaluated using angio-IMR was associated with LGE and long-term prognosis in patients with DCM. Further investigations are needed to elucidate the relationship among CMD, LGE, and prognosis.

ABSTRACT Background The long‐term prognosis of patients with heart failure (HF) remains poor. Most patients with HF are older, and multiple factors involved in geriatric syndromes are associated with worse long‐term prognosis. Sarcopenia is a major component of geriatric syndrome. Early diagnosis and therapeutic intervention for sarcopenia are clinically important in patients with HF; however, the prevalence and long‐term prognostic impact of sarcopenia in patients with stage B HF remain unclear. This study aimed to determine the prevalence of sarcopenia in older patients with stage B HF and its impact on the long‐term prognosis. Methods The PAPRIKA‐HF study was a multicenter, prospective study that enrolled outpatients ≥ 65 years who were diagnosed with stage B HF. Sarcopenia was assessed based on the Asian Working Group for Sarcopenia 2019 diagnostic criteria. The primary endpoint was a composite endpoint (all‐cause mortality, incident myocardial infarction, or hospitalization for heart failure) of > 2 years. Results Among 312 patients (mean age: 78.2 ± 6.5 years, 45% female), 17.7% (56 of 312 patients) had sarcopenia. The rate of the composite endpoint over 2 years was significantly higher in patients with sarcopenia than in those without (25.0% vs. 2.7%, log‐rank test, p < 0.0001). Multivariate analysis using the Cox proportional hazards model showed that sarcopenia was an independent predictor of long‐term prognosis (hazard ratio: 5.78, 95% confidence interval: 2.16–15.43, p < 0.001). Conclusions Sarcopenia was associated with a worse long‐term prognosis in older patients with stage B HF, highlighting the importance of early diagnosis of sarcopenia.

BACKGROUND: Low serum albumin levels indicate frailty and are strong predictors of poor prognosis after mitral transcatheter edge-to-edge repair (M-TEER); however, albumin levels are expected to improve in response to treatment for mitral regurgitation. No reports have elucidated the clinical effects of albumin changes after M-TEER. Thus, we aimed to explore the association between early albumin changes and clinical outcomes after M-TEER and to identify the associated factors. METHODS: Data from 2695 patients enrolled in a Japanese multicenter registry whose serum albumin levels were measured before and 1 month after undergoing M-TEER were retrospectively reviewed. Changes in albumin (Δ-albumin) were calculated and divided into 2 groups, namely improved albumin (Δ-albumin >0) and worsening albumin (Δ-albumin ≤0) groups. The incidence, predictors, and clinical outcomes associated with early albumin changes were investigated. RESULTS: After M-TEER, albumin levels improved in 56.1% of the patients (n=1512). The independent predictors of worsening Δ-albumin comprised old age, acute procedure success not achieved, higher Clinical Frailty Scale, higher hemoglobin, impaired renal function, and preprocedural higher albumin levels (all P<0.05). Improved Δ-albumin was independently associated with reduced all-cause mortality after M-TEER (hazard ratio [HR], 0.62 [95% CI, 0.52-0.75], P<0.001). Additionally, improved Δ-albumin was associated with a lower competing risk of heart failure hospitalization (HR, 0.78 [95% CI, 0.64-0.94], P=0.01). CONCLUSIONS: Early improvement in Δ-albumin may serve as a measure of procedural benefits and a surrogate marker for predicting clinical outcomes after M-TEER.

BACKGROUND AND AIMS: Atrial functional mitral regurgitation (AFMR) commonly affects elderly and frail individuals. The prognostic impact of transcatheter edge-to-edge repair (TEER) for AFMR has not been investigated. METHODS: Patients with AFMR who underwent TEER were selected from the OCEANMitral registry, and medically managed controls were selected from the REVEALAFMR registry, using an identical AFMR definition. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization. The secondary endpoint was all-cause mortality. RESULTS: A total of 1,081 patients (mean age 80.1±8.2 years, 60.5% female) with moderate or severe AFMR were included, of whom 441 underwent TEER and 640 remained on medical treatment. Overlap weighting based on propensity score yielded well-balanced characteristics (n=441 vs. 640; all standardized mean differences <0.01), where TEER was associated with a lower incidence of the primary (hazard ratio [HR] 0.65 [0.43-0.99], p=0.044) and secondary endpoints (HR 0.58 [0.35-0.99], p=0.044). In an exploratory subgroup analysis, favorable outcomes might be pronounced in patients with ≤mild residual AFMR after TEER, while event rates in those with ≥moderate residual AFMR were comparable to the medication group. As sensitivity analyses, inverse probability of treatment weighting (n=158 vs. 173), propensity score matching (n=104 vs. 104), and multivariable Cox regression (n=441 vs. 640) all confirmed favorable associations of TEER with both endpoints. CONCLUSIONS: In real-world data, TEER for patients with moderate or severe AFMR was associated with a lower incidence of adverse events compared with medical treatment.

Abstract Reducing total ischemic time in ST-elevation myocardial infarction (STEMI) is crucial for improving outcomes. While procedural time during primary percutaneous coronary intervention (PCI) is critical, strategies to shorten it need to be explored. To examine whether the single-catheter PCI (SC-PCI) method using a universal guiding catheter, Ikari-Left curve, without catheter exchange reduces PCI time compared to conventional PCI (C-PCI). The Speedy PCI study is a prospective, multicenter, randomized trial comparing SC-PCI versus C-PCI. The primary endpoint was the time from sheath insertion to first device activation (S2B) time. Secondary endpoints included door-to-balloon time, total ischemia time, fluoroscopy time, contrast volume, hospital expenses, and 30-day mortality. A total of 380 patients (SC-PCI: 194; C-PCI: 186) were analyzed. Both groups had high primary PCI success rates (92.3 vs. 91.9%, p = 0.74) and similar radial access usage (higher than 97%). SC-PCI method showed a significantly shorter S2B time (15.8 ± 10.9 min) compared to the C-PCI method (18.7 ± 10.6 min, p = 0.007) with reduced number of total catheters used (1.2 ± 0.6 vs. 2.7 ± 0.7, p < 0.0001, respectively). No cases of coronary dissection caused by the guiding catheter were observed in the SC-PCI method. Clinical outcomes at 30 days and 1-year follow-up, including all-cause mortality and stroke rates, were similar between the groups. The SC-PCI method using the Ikari curve demonstrated a significant reduction in PCI procedure time while maintaining safety and primary PCI success in primary PCI for STEMI. Graphical abstract

BACKGROUND: No studies have compared the outcomes of using the SAPIEN3 Ultra RESILIA (S3UR) balloon-expandable valve or the Navitor self-expandable valve for transcatheter aortic valve replacement (TAVR) in patients with a small annulus. OBJECTIVE: This study aimed to compare in-hospital outcomes and hemodynamic performance of S3UR and Navitor TAVR in patients with an annulus area ≤ 430 mm2. METHODS: We retrospectively analyzed the Optimized Transcatheter Valvular Intervention-Transcatheter Aortic Valve Implantation registry data. The endpoints included technical success, device success (per Valve Academic Research Consortium 3 criteria), and post-TAVR echocardiographic function (severe prosthesis-patient mismatch [PPM], aortic-valve mean pressure gradient [mAVPG] ≥ 20 mmHg, and para-valvular leakage [PVL] ≥ mild). We adjusted for differences in baseline characteristics using multivariate logistic regression and propensity score analyses. RESULTS: Of 1224 patients, 706 (57.7 %) underwent TAVR using S3UR. The Navitor TAVR group had higher rates of mild or severe PVL (13.3 % vs. 36.4 %), postoperative pacemaker implantation (5.2 % vs. 13.1 %), and ischemic stroke (0.7 % vs. 2.5 %), compared with the S3UR TAVR group. Both groups had similar moderate or severe PPM rates; however, fewer patients in the Navitor TAVR group had a mAVPG >20 mmHg compared with those in the S3UR TAVR group. CONCLUSIONS: TAVR using S3UR resulted in lower rates of ischemic stroke, pacemaker implantation, and PVL compared with that using Navitor. The incidence of moderate or severe PPM was similar in both groups; however, the Navitor TAVR group showed superior hemodynamic valve performance, compared with S3UR TAVR group.

For severe aortic stenosis (AS) patients awaiting valve replacement, managing acute decompensated heart failure (ADHF) is crucial due to poor prognosis. The LOHAS registry evaluated the effect of tolvaptan in patients (mean age: 85 years) with severe AS and ADHF, demonstrating stable hemodynamics and sufficient diuresis. We investigated predictors of rapid successful decongestion. In the LOHAS study, eligible patients received tolvaptan (7.5 mg) on day 1 plus standard ADHF treatments. Patients were divided based on decongestion achievement on day 4. Of 59 enrolled, 35 (59%) achieved decongestion (decongestion group), and 24 (41%) remained congested (congestion group). Changes in body weight, renal function, and hemodynamics were comparable between groups over the first 4 days. However, the maximum inferior vena cava (IVC) diameter at admission was significantly larger in the decongestion group than the congestion group (12.6 ± 6.3 vs. 7.6 ± 4.8 mm, p = 0.007). ROC analysis revealed a cut-off of 11 mm for maximum IVC diameter to predict decongestion on day 4 (AUC: 0.73, 95% CI 0.58-0.88). In-hospital mortality was lower in the decongestion group (0% vs. 13%, p = 0.06). In conclusion, in this high-risk severe AS and ADHF population, adding tolvaptan to standard therapy may rapidly improve decompensation if patients have a sufficiently expanded IVC at admission. Maximum IVC diameter could predict successful decongestion with tolvaptan.

Background: Cardiac rehabilitation using mobile health is increasingly being described as effective in improving exercise habits and physical function. However, the effectiveness of combined mobile health and hospital-based cardiac rehabilitation in older patients with cardiovascular disease is unknown. Objective: To investigate the effect of a wearable watch device combined with hospital-based cardiac rehabilitation in older patients with cardiovascular disease compared with those with usual care. Methods: A randomized, controlled trial was conducted in patients with cardiovascular disease aged ⩾60 years who underwent hospital-based cardiac rehabilitation. The patients were randomized 1:1 in those with a wearable watch (Fitbit Versa 3) or usual care. During out-of-hospital cardiac rehabilitation, patients with a wearable watch were advised to check their heart rate with a wearable watch and to target their physical activity at the heart rate determined by cardiopulmonary exercise testing. The primary endpoint was a change in physical activity obtained from the International Physical Activity Questionnaire (metabolic equivalents [METs]-minute/week) between the 2 groups during 12 weeks. Results: Among 39 patients (median age = 73 years, 82% men), the change in physical activity was significantly greater in patients with a wearable watch than in those with usual care (median: 2073 [1155-4400] vs 148 [−1261-899] METs-minute/week; analysis of covariance; P  < .001). In patients with a wearable watch, 6-minute walk distance, the peak oxygen uptake, peak METs, and anaerobic threshold were significantly improved, whereas no significant increase was observed in patients with usual care from baseline to 12 weeks. Conclusions: In older patients with cardiovascular disease, a wearable watch device combined with hospital-based cardiac rehabilitation increases physical activity and improves exercise capacity outside of hospital.

Abstract Evaluation of calcified lesions by intravascular imaging has revealed that atherectomy devices have only limited impact. However, subsequent use of coronary intravascular lithotripsy (IVL) may increase treatment effectiveness without increasing risk of complications. This study was designed to evaluate the safety and effectiveness of IVL use after atherectomy in severely calcified coronary lesions as pre-treatment for drug-eluting stents (DES). The Dual-Prep registry is a multicenter, prospective registry of consecutive image-guided percutaneous coronary interventions (PCI). The primary effectiveness and safety endpoints were procedural success (residual stenosis < 50% by quantitative coronary angiography) without an in-hospital major adverse cardiac event (MACE) and 30-day freedom from MACE, respectively. Baseline vessel calcification score and final DES expansion were evaluated by optical coherence tomography (OCT). A total of 118 patients with 120 lesions were enrolled at 20 sites. The calcification score of lesions after atherectomy by core-lab assessment was 4.0 in all cases. Rotational atherectomy was applied prior to IVL in 83.9% cases with mean burr size of 1.57 ± 0.20 mm; IVL was subsequently successfully delivered in all cases (mean balloon diameter 3.02 ± 0.45 mm), followed by DES deployment (mean diameter 3.19 ± 0.51 mm, length of 36.3 ± 16.0 mm). The primary efficacy and safety endpoints were met in 98.3% and 98.3% of cases, respectively. A DES expansion index < 0.8 was seen in 42.2%, and an eccentricity index < 0.7 was not observed in any patient. In severely calcified lesions, image-guided atherectomy followed by IVL lesion preparation demonstrated high procedural success rates and satisfactory non-eccentric stent expansion. This approach may be considered for lesions where an ‘IVL-first’ strategy may not be feasible. jRCT1032230384 (Oct 7, 2023). Graphical abstract Dual-Prep registry : atherectomy + IVL before DES implantation strategy for calcified lesion (Calc score ≥ 3 after atherectomy)

In this updated expert consensus document, the methods for the quantitative measurement and morphologic assessment of optical coherence tomography (OCT) / optical frequency domain imaging images (OFDI) are briefly summarized. The focus is on the clinical application and the clinical evidence of OCT / OFDI to guide percutaneous coronary interventions.

BACKGROUND: Drug-coated balloon (DCB) are effective treatment options for patients with coronary artery disease and using of scoring or cutting balloon before the DCB usage were recommended. However, the effectiveness of lesion preparation with cutting balloons (CB) followed by DCB (CB + DCB) has not been evaluated before. AIMS: The aim of the current study was to compare the biological effect of various types of balloon angioplasty in a healthy rabbit iliac artery model. METHODS: Each of the four kinds of treatments as balloon angioplasty (BA), CB alone, DCB alone, and CB + DCB were performed in the healthy iliac arteries of 12 rabbits, which were euthanized after 14 days. The treated iliac arteries were sequentially cut, stained with hematoxylin and eosin and Movat Pentachrome, and histopathologically evaluated. RESULTS: The depth of medial smooth muscle cell (SMC) loss score, an indicator of drug effect, was highest with CB + DCB, followed by DCB, CB, and BA (CB + DCB vs. DCB vs. CB vs. BA: 3.83 (3.67-4.00) vs. 3.17 (2.67-3.67), 1.67 (1.67-2.08) vs. 1.50 (1.00-1.67), p < 0.0001). The angle with severe SMC loss was also the highest with CB + DCB group, followed by DCB group, CB group, and BA group (123.7 (104.5-132.2) vs. 52.1 (34.7-100.6), 0.0 (0.0-14.2) vs. 0.0 (0.0-0.0), respectively, p < 0.0001), suggesting a higher drug effect in CB + DCB compared with DCB alone. CONCLUSIONS: The drug effect of DCB was enhanced when CB was used before DCB treatment, suggesting the effectiveness of the combination therapy of CB and DCB.

Identification of vulnerable plaques is important for reducing future cardiovascular events. This study aimed to investigate optimal modalities other than intravascular imaging in evaluating vulnerable plaques. We prospectively evaluated 105 non-culprit coronary lesions by CCTA imaging and near-infrared spectroscopy-intravascular ultrasound in 32 patients with acute coronary syndrome. Angiographically-derived ΔQFR and ΔFFRCT were measured as the difference in QFR and FFRCT across the stenosis. A receiver operating characteristic curve analysis was performed to determine the optimal cutoff values of angiographically- and CCTA-derived plaque features for a maxLCBI4mm ≥ 400. The best cutoff values for ΔQFR and ΔFFRCT to predict a maxLCBI4mm ≥ 400 were 0.05 and 0.06, respectively. ΔQFR and ΔFFRCT values and percent diameter stenosis on QCA or CCTA were associated with a maxLCBI4mm ≥ 400 (both P < 0.05). The combination of ΔFFRCT ≥ 0.06 and plaque density predicted a maxLCBI4mm ≥ 400 with 89.4% sensitivity and 84.5% specificity (area under the curve, 0.90; P < 0.0001). There was no significant difference in area under the curve values between ΔQFR and plaque density + ΔFFRCT ≥ 0.06 (0.92 vs. 0.90, P = 0.50). In the diagnosis of vulnerable plaques in acute coronary syndrome, the combination of ΔFFRCT and plaque density shows a diagnostic capability similar to that of ΔQFR in non-culprit lesions.

BACKGROUND: The impact of malnutrition on clinical outcomes in patients with takotsubo syndrome (TTS) is poorly understood. The purpose of this study was to investigate the relationship between malnutrition on admission and 30-day adverse events in patients with TTS. METHODS: We retrospectively evaluated 124 consecutive patients admitted for TTS at our hospital from April 2013 to July 2023. Malnutrition was assessed at admission using the Geriatric Nutritional Risk Index (GNRI), which is an objective and simple nutritional assessment method. Malnutrition was defined as GNRI <92. We defined 30-day adverse events as the composite of all-cause death, acute heart failure, cardiogenic shock, life-threatening arrhythmia, thrombotic events, and stroke. The primary endpoint was the comparison of the 30-day adverse event rates between patients with and without malnutrition. RESULTS: The median age was 78.0 (70.0-83.0) years, and 77 % of the patients were women. The median GNRI was 90.8 (81.5-98.0) and 55 % had malnutrition. The 30-day adverse events were shown in 64 patients. Compared with patients without malnutrition, the 30-day adverse event rate was significantly higher in those with malnutrition (32 % vs. 68 %, respectively; log-rank test p = 0.0001). The multivariable Cox proportional hazards model revealed that malnutrition was independently associated with high 30-day adverse event rates adjusted by age, female sex, malignancy, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hazard ratio: 1.97, 95 % confidence interval: 1.08-3.58; p = 0.02). CONCLUSIONS: Malnutrition at admission was associated with high 30-day adverse event rates. Early identification and a considered treatment strategy for malnutrition are important in patients with TTS.

AIMS: The Tpeak-Tend interval on electrocardiogram may be a predictor of worse outcomes in Takotsubo syndrome (TTS), but the mechanisms have not been fully determined. This study aimed to investigate the relationships between the corrected Tpeak-Tend (cTp-e) interval and coronary microvascular-dysfunction (CMD) assessed by the angiography-derived index of microvascular resistance (Angio-IMR) and the in-hospital prognosis in patients with TTS. METHODS AND RESULTS: We retrospectively evaluated 111 consecutive patients admitted for TTS who underwent coronary angiography at Kindai University Hospital from October 2009 to July 2023. The Tpeak-Tend interval was defined as the time interval between the peak and the end of the T wave in electrocardiogram lead V5 on admission. Angio-IMR was assessed from aortic pressure, quantitative flow ratio (QFR), vessel length and hyperemic velocity using the formula described in validation studies. QFR, vessel length and hyperemic velocity was derived from coronary angiography and QAngio XA 3D software package. The degree of CMD was assessed by the maximum Angio-IMR value in each of the three coronary arteries. The primary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and Angio-IMR. The secondary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and in-hospital adverse cardiovascular events (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmia, thrombotic events, stroke and all-cause death). The median age was 77.5 [71.0-83.0] years, and most patients were women (82.0%). The median cTp-e interval was 114.5 [91.2-147.0] ms. The patients were categorized according to the tertiles of the cTp-e interval (T1: 52.4-96.9 ms; T2: 100.1-129.1 ms; T3: 131.7-309.8 ms). There was a stepwise increment in the values of maximum Angio-IMR in each of the three coronary arteries in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 16.1 [14.7-19.3] vs. 21.8 [16.0-31.1] vs. 29.0 [27.2-31.9], P < 0.001). In-hospital adverse cardiovascular events occurred in 53 of 111 patients (47.7%). There was a stepwise increment in the incidence of in-hospital adverse cardiovascular events in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 27.1% vs. 54.1% vs. 62.2%, P = 0.007). The multivariable analysis showed that prolonged cTp-e interval (OR: 1.30; 95% CI: 1.12-1.56; P < 0.001) was independent predictors of in-hospital adverse cardiovascular events. CONCLUSIONS: The Tpeak-Tend interval on admission reflected CMD and predicts in-hospital adverse cardiovascular events in patients with TTS.

BACKGROUND: The relationship between protein intake and the long-term prognosis of elderly patients with heart failure remains poorly understood. We investigated the association between predischarge protein intake and long-term prognosis in hospitalized elderly patients with heart failure. METHODS AND RESULTS: A single-center, retrospective analysis of hospitalized patients aged ≥65 years with heart failure and reduced ejection fraction was conducted. Protein intake was evaluated by nutritionists based on visual measurements of the percentage of dietary intake obtained for 7 days before discharge by a nurse. A cutoff of 1.2 g/kg/day protein intake was used to compare the incidence of a composite endpoint, including all-cause mortality and heart failure rehospitalization within 1 year. Among the 100 patients (median age 79 years; 47% male), 56% had low protein intake (<1.2 g/kg/day). Patients with low protein intake had a significantly higher rate of composite endpoints than those with high protein intake (50% vs. 20%; log-rank test P=0.03). Multivariable Cox proportional hazards model revealed that low protein intake was independently associated with long-term prognosis with a hazard ratio of 2.73 and a 95% confidence interval of 1.10-6.80 (P=0.03). CONCLUSIONS: Low protein intake in the predischarge phase was associated with long-term prognosis in hospitalized elderly patients with heart failure and reduced ejection fraction.

BACKGROUND: The initial outcomes of transcatheter aortic valve replacement in patients with left ventricular outflow tract calcification are poor. Furthermore, balloon-expandable transcatheter aortic valve replacement is associated with an increased risk of annular rupture, and self-expandable transcatheter aortic valve replacement is associated with worse post-operative residual paravalvular leakage grades. Therefore, developing an optimal method for transcatheter aortic valve replacement for patients with left ventricular outflow tract calcification is desirable. CASE SUMMARY: We present two cases of successful balloon-expandable transcatheter aortic valve replacement, wherein the transcatheter heart valve was implanted above the left ventricular outflow tract calcification to avoid annular rupture and paravalvular leakage, and one case each of balloon-expandable and self-expandable transcatheter aortic valve replacements, wherein the transcatheter heart valve was implanted at a normal height. Although annular rupture did not occur in any of the cases, more-than-mild paravalvular leakage persisted post-operatively in cases where the transcatheter heart valve was placed at a normal height. DISCUSSION: Annular rupture is more likely to occur in areas with high calcification at the joint than in noncalcified areas. Furthermore, the greater the calcification in the landing zone of the transcatheter heart valve, the more the paravalvular leakage persists. Therefore, high implantation of transcatheter heart valves above the left ventricular outflow tract calcification can be an effective method to avoid annular rupture and paravalvular leakage.

BACKGROUND AND AIMS: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stents. METHODS: In the STOPDAPT-3, patients with acute coronary syndrome or high bleeding risk (HBR) were randomly assigned to either 1-month dual antiplatelet therapy with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. RESULTS: Of the 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, acute coronary syndrome 74.6%, and high bleeding risk 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint [4.5 and 4.5 per 100 person-year, hazard ratio 1.00 (95% confidence interval .77-1.30), P = .97], and bleeding endpoint [2.0 and 1.9, hazard ratio 1.02 (95% confidence interval .69-1.52), P = .92]. CONCLUSIONS: Aspirin monotherapy compared with clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after percutaneous coronary intervention with drug-eluting stents (STOPDAPT-3 ClinicalTrials.gov number, NCT04609111).

BACKGROUND: To prevent the further development of cardiovascular diseases, it is a growing global priority to detect untreated hypertension in patients and ensure adequate blood pressure control via drug therapy. However, few effective tools that facilitate the initiation of antihypertensive medications among such patients have been identified. OBJECTIVE: We aimed to determine whether a mobile health (mHealth) app facilitates the initiation of antihypertensive medications among patients with untreated hypertension. METHODS: We analyzed a large longitudinal integrated database mainly comprised of data from middle-aged, employed people and their families. The database contained data from health checkups, health insurance claims, and the mHealth app kencom. kencom is used to manage daily life logs (eg, weight, number of steps) and to provide health information tailored to customers. Patients with untreated hypertension were identified using the baseline health checkup data, and follow-up health checkups were conducted to identify the rate of initiation of antihypertensive medications between mHealth app users and nonusers. Antihypertensive medication status was confirmed via a questionnaire administered during the medical checkup as well as a review of the health insurance claims database. We conducted a modified Poisson regression analysis, weighted by inverse probability of treatment weighting, to examine the effect of mHealth app usage on the initiation of antihypertensive medications. Additionally, data from four lifestyle questionnaires from the baseline and follow-up health checkups were collected to evaluate lifestyle modifications that could be attributed to the mHealth app. RESULTS: Data were collected from 50,803 eligible patients (mean age 49, SD 9 years; men n=39,412, 77.6%; women n=11,391, 22.4%) with a median follow-up period of 3.0 (IQR 2.3-3.1) years. The rate of initiation of antihypertensive medications was significantly higher in the mHealth app user group than in the nonuser group: 23.4% (3482/14,879) versus 18.5% (6646/35,924; P<.001), respectively. The risk ratio of mHealth app usage for initiated antihypertensive medications was 1.28 (95% CI 1.23-1.33). Among those who did not intend to improve their lifestyle habits such as exercise and diet at baseline, the rate of lifestyle improvement at follow-up was compared between mHealth app users and nonusers, using data from the questionnaires; mHealth app users demonstrated a significantly higher rate of lifestyle changes than nonusers. CONCLUSIONS: For patients with untreated hypertension, the use of the mHealth app kencom, which was not dedicated to hypertension treatment, was associated with a higher initiation of antihypertensive medications.

BACKGROUND: The mortality rate of patients with cardiogenic shock (CS) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) combined with Impella (ECPELLA) support remains high. Inhaled nitric oxide (iNO) improves right ventricular (RV) function, resulting in increased Impella flow, which may facilitate early withdrawal of VA-ECMO and improve survival. This study investigated the prognostic impact of iNO therapy in ECPELLA patients. METHODS: We retrospectively analyzed the data of consecutive patients with CS supported by ECPELLA from September 2019 to March 2024 at our hospital. Changes in pulmonary artery pulsatility index (PAPi) and Impella flow over time were evaluated, and VA-ECMO withdrawal rate, time to withdrawal, and 30-day survival were compared between ECPELLA patients with and without iNO therapy. RESULTS: Of the 48 ECPELLA patients, 25 were treated with iNO. There were no significant differences between the groups in baseline characteristics or lactate levels at mechanical circulatory support induction. Patients with iNO therapy demonstrated significant improvements in the PAPi over time and a trend toward increased Impella flow, as well as a significantly higher VA-ECMO withdrawal rate (88% vs. 48%, P = 0.002) and a shorter time to VA-ECMO withdrawal (5 [3-6] days vs. 7 [6-13] days, P = 0.0008) than those without iNO therapy. Kaplan-Meier analysis demonstrated that the 30-day survival rate was significantly higher in patients with iNO than in those without (76% vs. 26%, P = 0.0002). CONCLUSIONS: iNO therapy in patients with CS requiring ECPELLA was associated with short-term prognosis by improving RV function and facilitating weaning from VA-ECMO. Trial registration Retrospectively registered in UMIN-CTR (Reference No. R00006352).

BACKGROUND: The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking-a gap addressed in the current study. METHODS: From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis. RESULTS: Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; P = .02, 7.7% vs. 30.4%; P = .02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; P < .01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days (odds ratio [OR], 0.009; 95% confidence interval [CI], 0.006-0.012; P < .01), superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; P < .01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; P = .039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; P < .01) as delayed endothelial coverage predictors. CONCLUSIONS: Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.

BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

BACKGROUND: East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve implantation (TAVI) outcomes in Asian patients with a large annulus. OBJECTIVES: This study aimed to compare the short- and long-term outcomes of TAVI using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. METHODS: The study retrospectively analyzed the data from the OCEAN-TAVI (Optimized Transcatheter Valvular Intervention Transcatheter Aortic Valve Implantation) registry. A large annulus was defined by an annular area ≥500 mm2 and an average diameter ≥25 mm as measured by computed tomography. The primary endpoint was 3-year all-cause mortality. Secondary endpoints were 3-year heart failure rehospitalization (HFR) after TAVI, short-term outcomes of TAVI, and changes in valve function 2 years after TAVI. RESULTS: Among 773 patients, 671 underwent BEV TAVI. The SEV TAVI group showed a significantly higher incidence of greater than moderate paravalvular leakage (PVL) (P < 0.001), and an increased pacemaker implantation rate (P = 0.035). The incidence of prosthesis-patient mismatch did not differ between the 2 groups. The Kaplan-Meier curve showed no significant differences in 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and echocardiographic valve function at 2 years post-TAVI did not differ between the 2 groups. CONCLUSIONS: The lack of differences in postoperative valve performance and long-term prognosis between BEV TAVI and SEV TAVI highlights the importance of selecting valves that can reduce the pacemaker implantation rate and PVL grade in the acute phase in patients with a large annulus. (Optimized Transcatheter Valvular Intervention Transcatheter Aortic Valve Implantation [OCEAN-TAVI]; UMIN000020423).

BACKGROUND: Transcatheter edge-to-edge mitral valve repair is now available in many countries and has achieved favourable therapeutic outcomes. However, there have been no reported cases of clip opening while locked (COWL) during the acute phase using the MitraClip G4 system (Abbott, Abbott Park, IL, USA). CASE SUMMARY: We present two cases of COWL occurring at different phases: one immediately after clip release and the other 2 days post-procedure. In both cases, the initial treatment involved the use of the XTW system. Subsequently, an additional XT system was deployed for the deterioration of mitral regurgitation caused by COWL, without any complications. DISCUSSION: The MitraClip G4 system offers four size variations, providing a larger grasping area and increased flexibility for accessing complex lesions. Furthermore, the complication rate decreased with increasing operator experience and device generation. However, it has been reported that COWL can occur after the clip is deployed during TEER. Although the mechanism of COWL is unclear, the nature and mobility of the valve leaflets and the product specificity of the MitraClip may be involved.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. IgG4-RD has also been reported in coronary arteries as periarteritis. IgG4-related coronary periarteritis may cause coronary artery aneurysms, and IgG4-related coronary artery aneurysms (IGCAs) are life-threatening. We describe a case of a patient with IGCA that highlights the usefulness and limitations of various IGCA evaluation modalities and provides insight into disease pathophysiology. CASE SUMMARY: A 60-year-old man with IgG4-RD diagnosed 2 years before and with IGCA at the proximal right coronary artery (RCA) on coronary angiography (CAG) 9 months prior to admission to the hospital presented with acute coronary syndrome. Emergent CAG revealed the rapid progression of IGCA at the RCA, an obstruction of the diagonal branch, and stenosis of the left anterior descending artery (LAD) and the high lateral branch (HL). The patient underwent percutaneous coronary intervention for the diagonal branch. The RCA aneurysm was resected and bypassed with a saphenous vein graft (SVG); coronary bypass grafting (left internal mammary artery to LAD and SVG to HL) was performed. Pathological findings showed inflammatory cell infiltration and disruption of the elastic plate. CONCLUSION: IGCAs require careful follow-up with computed tomography scans for early detection of aneurysmal enlargement.

BACKGROUND: Drug-coated balloons (DCBs) are important treatment options for coronary artery disease; however, randomised controlled trials comparing various DCB technologies are sparse, and further investigations are needed. AIMS: This preclinical study aimed to histologically and biologically compare the drug effects and safety of a low-dose paclitaxel-coated DCB (PCB; AGENT), a regular-dose PCB (SeQuent Please NEO) and a sirolimus-coated DCB (SCB; MagicTouch). METHODS: The DCBs were inflated in the healthy iliac arteries of 18 rabbits, which were euthanised after 28 days. The treated iliac arteries and distal skeletal muscles were histopathologically evaluated, and drug concentrations were measured. RESULTS: In the histopathological evaluation, the medial smooth muscle cell loss score regarding depth, an indicator of drug efficacy, was significantly higher with AGENT and SeQuent Please NEO than with MagicTouch (4.0 [3.6-4.0] vs 3.7 [3.7-4.0] vs 2.2 [2.0-2.4]), with significant differences in comparisons between AGENT and MagicTouch (p<0.01) and between SeQuent Please NEO and MagicTouch (p<0.01). AGENT and SeQuent Please NEO showed comparable drug concentrations in the treated artery (p=0.61). In contrast, the drug concentrations in distal skeletal muscles were the highest for MagicTouch, followed by SeQuent Please NEO and AGENT (28.07 [13.19-52.46] ng/mg vs 0.66 [0.22-3.76] ng/mg vs 0.25 [0.04-3.23] ng/mg, respectively). CONCLUSIONS: This study demonstrated that PCBs might have higher efficacy and lower drug concentrations in distal skeletal muscles than the MagicTouch SCB. The efficacy of the AGENT low-dose PCB and the SeQuent Please NEO regular-dose PCB was comparable.

BACKGROUND: There are a few case reports regarding transcatheter aortic valve implantation (TAVI) for deteriorated surgical homograft. CASE SUMMARY: We present a case of severe structural valve deterioration (SVD) of homograft surgical aortic valve presenting severe aortic regurgitation in an 84-year-old man with decompensated heart failure. We performed TAVI in homograft valve using 23 mm SAPIEN3 Ultra RESILIA. The resulting grade of paravalvular regurgitation was trace, the post-operative effective orifice area (EOA) was 1.66 cm2 (index EOA: 1.19 cm2/m2), and device success was achieved. DISCUSSION: Stented bioprosthetic valves are more commonly implanted than mechanical and stentless bioprosthetic valves. In the 1980s and the early 1990s, homografts became particularly popular as alternatives to stented valves. There are several reports of TAVI for homograft SVD, but the paravalvular leakage grade is worse than that of redo-surgical aortic valve replacement, although the mortality rate is lower. However, the valves used in these reports were from older valves such as SAPIEN XT or SAPIEN3. There are no reports using SAPIEN3 Ultra RESILIA with a significant reduction in paravalvular leak due to an external textured polyethylene terephthalate skirt extending 40% higher above the valve inflow than the classical SAPIEN3, which is now available. Transcatheter aortic valve implantation using SAPIEN3 Ultra RESILIA showed good therapeutic efficacy.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Transcatheter structural heart interventions have drastically evolved over the past 2 decades. However, most catheterization procedures require the deployment of devices in the body; therefore, the adhesion of thrombi to those devices is a major problem, resulting in the requirement of a period of postprocedural antithrombotic regimen. However, in recent years, bleeding associated with these antithrombotic therapies has also become a major concern, attracting the attention of investigators. This is complicated by the fact that patients at high thrombotic risk are also at high bleeding risk, making the issue of administrating antithrombotic therapy challenging. The objective of this review was to identify the important issues and summarize the current status of postoperative antithrombotic therapy and assessment of the bleeding risk following transcatheter structural heart interventions such as transcatheter aortic valve replacement, transcatheter edge-to-edge repair, and transcatheter left atrial appendage occlusion.

Recent studies have showed that asymptomatic cerebral infarction (ACI) developed in a reasonable number of patients after cardiac catheterization. However, no study has investigated the long-term prognostic impact of ACI after cardiac catheterization. We investigated whether ACI after cardiac catheterization affects long-term mortality and subsequent cardiovascular events.We retrospectively enrolled patients who underwent cardiac catheterization before cardiac surgery and cerebral diffusion-weighted magnetic resonance imaging (DWI). The incidence and clinical features of ACI were investigated. The long-term prognosis, including all-cause mortality and subsequent major cardiovascular events (MACE; all-cause mortality, stroke, acute myocardial infarction, fatal arrhythmia, and hospitalized heart failure), was also assessed.A total of 203 patients were enrolled. Of these, 10.3% had ACI diagnosed by DWI. There were no differences in baseline characteristics between patients with and without ACI, except more frequent history of symptomatic stroke in patients with ACI. In the Kaplan-Meier analysis during a median follow-up of 1009 days, the patients with ACI showed worse mortality and a slightly higher occurrence of MACE compared with those without ACI (P = 0.01 and P = 0.08, respectively). In addition, ACI was a prognostic marker independent of age, surgery type, and history of stroke.ACI after cardiac catheterization frequently developed and was also associated with long-term prognosis. It may be an independent prognostic marker in high-risk patients who underwent subsequent cardiac surgery.

BACKGROUND: There are limited data on the impact of intracardiac echocardiography (ICE)-guided transcatheter aortic valve replacement (TAVR) on the new permanent pacemaker implantation (PPMI) rate. OBJECTIVES: This study investigated the feasibility and outcome of transjugular ICE (TJ-ICE) -guided TAVR, by visualizing the relationship between the membranous septum (MS) and the transcatheter aortic valve (TAV). METHODS: Among patients with severe aortic stenosis who underwent TAVR between February 2017 and June 2020, this study enrolled a total of 163 patients with TJ-ICE-guided TAVR. MS length was measured by ICE. The primary endpoint of this study was the incidence of new PPMI at 30 days. RESULTS: The mean age of the patients in this study was 84.9 ± 4.6 years, and 71.2% of the patients were female. Device success was 96.3% with TJ-ICE guidance. A TJ-ICE-related complication occurred in 1 case (0.6%). The median length of the MS was 5.8 mm (IQR: 5.0-6.9 mm). Excellent intraobserver (intraclass correlation coefficient [ICC]: 0.94; 95% CI:0.79-0.98; P < 0.001) and interobserver (ICC: 0.93; 95% CI: -0.05 to 0.98; P < 0.001) agreements were shown. The new PPMI rate was 6.7% at 30 days without a significant difference between balloon-expandable valves and self-expandable valves (3.4% vs 8.7%; P = 0.226). Patients with a TAV implantation depth less than MS length had a significantly lower incidence of new PPMI compared with patients with a TAV implantation depth greater than MS length (2.1% vs 13.4%; P = 0.005), regardless of baseline right bundle branch block presence (6.7% vs 66.7%; P = 0.004) or absence (1.2% vs 8.2%; P = 0.041). CONCLUSIONS: TJ-ICE-guided TAVR demonstrated remarkable feasibility and safety. The TJ-ICE-guided final TAV position had a significant impact on the new PPMI rate. (Tokai Valve Registry; UMIN000036671).

BACKGROUND: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. METHODS: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 μm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. RESULT: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p < 0.05). In the POT-SBD group, worsening ISA after SBD was prominent at the distal bifurcation. The BA was an independent predictor of major ISA (odds ratio 1.04, 95% confidence interval 1.00-1.07, p < 0.05) with a cut-off value of 59.5° (p < 0.05). However, the cases treated with optimal POT in the short BA (<60°) indicated the lowest incidence of major ISA. In the KBT group, BA had no significant impact. CONCLUSION: A wide BA has a potential risk for the occurrence of major ISA after POT followed by SBD in coronary bifurcation stenting.

BACKGROUND: Early prediction of aorta-related events is important for determining subsequent treatment strategies in patients with acute aortic dissection. However, most studies evaluated long-term aortic growth rates by annual assessment. The purpose of our study was to determine whether the in-hospital growth rate of aortic volume was associated with aorta-related events. METHODS: We studied 116 patients with uncomplicated type B acute aortic dissection. We analyzed whether changes in aortic volume were associated with aorta-related events during a 5-year follow-up. According to the growth rate from admission to discharge, patients were divided into two groups: Increase >0 (aortic volume: n = 59, aortic diameter: n = 43) and Reduction ≤0 (aortic volume: n = 57, aortic diameter: n = 73) in maximum aortic diameter or aortic volume. The primary endpoint was the discriminative ability of the growth rate of aortic volume for aorta-related events. RESULTS: According to the evaluation of aortic volume changes, the Increase group had significantly higher aorta-related event rates than those in the Reduction group (49.2 % vs. 3.5 %, respectively; p < 0.001). Receiver operating characteristics analysis showed that the growth rate of aortic volume had a clearly useful discrimination, with an area under the curve of 0.84, whereas the discriminative ability of the growth rate of maximum aortic diameter was poor (area under the curve: 0.53). Multivariate analysis showed that the growth rate of aortic volume from admission to discharge was an independent predictor of aorta-related events (hazard ratio, 26.3; 95 % confidence interval, 2.04-286.49; p = 0.001). CONCLUSIONS: In-hospital evaluation of aortic volume was helpful to predict long-term aorta-related events in patients with uncomplicated type B acute aortic dissection.

BACKGROUND: Recently, mechanical support obtained with the combination of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and an Impella device, together referred to as ECPELLA, has been shown to be effective for acute myocardial infarction with cardiogenic shock. However, methods for withdrawing VA-ECMO in acute myocardial infarction cases complicated by right ventricular dysfunction are yet to be established. Here, we report the effective use of inhaled nitric oxide during the weaning of VA-ECMO from the ECPELLA management of a patient with acute myocardial infarction with cardiogenic shock. CASE SUMMARY: An 81-year-old man with an acute extensive anterior wall myocardial infarction with cardiogenic shock was supported with ECPELLA to improve his haemodynamics. During ECPELLA, the Impella device could not maintain sufficient flow. Echocardiography revealed a small left ventricle and an enlarged right ventricle, indicating acute right heart failure. Inhaled nitric oxide was initiated to reduce right ventricle afterload, which decreased pulmonary artery pressure from 34/20 to 27/13 mmHg, improved right and left ventricle sizes, and stabilized the Impella support. Afterward, VA-ECMO could be withdrawn because the Impella alone was sufficient for haemodynamic support. DISCUSSION: Inhaled nitric oxide improved right ventricle performance in a patient with severe myocardial infarction with right heart failure supported by ECPELLA. Thus, we suggest that inhaled nitric oxide facilitates the weaning of VA-ECMO from patients with refractory right ventricular dysfunction who are supported by ECPELLA.

OBJECTIVE: Poor below the knee (BTK) runoff is a predictor of stent failure after femoropopliteal artery endovascular treatment; however, the lack of pathological evaluation has prevented characterisation of stent failure. The study aimed to investigate the impact of poor BTK runoff and antithrombotic effect of the polymer of fluoropolymer coated paclitaxel eluting stents (FP-PESs) in a healthy swine femoropopliteal artery model. METHODS: FP-PESs and bare metal stents (BMSs) and FP-PES and polymer free paclitaxel coated stents (PF-PCSs) were implanted in bilateral femoral arteries of healthy swine (n = 6, respectively) following coil embolisation in both tibial arteries to induce poor BTK runoff. Histological assessment and intravascular imaging device evaluation was performed at one month. Japanese Association for Laboratory Animal Science approved the study protocol (reference number: IVT22-90). RESULTS: Optical coherence tomography showed significantly lower percent area stenosis in FP-PES compared with BMS (37.3%, interquartile range [IQR 25.6], 54.3% vs. 92.5%, IQR 75.5, 96.1%, respectively, p = .031), and PF-PCS (8.3%, IQR 4.5 - 27.0% vs. 31.2%, IQR 23.3 - 52.2%, respectively, p = .031). Histopathological evaluation demonstrated that thin fibrin attachment without restenosis was the most dominant neointimal tissue characteristic in FP-PES. On the other hand, neointimal tissue characteristics with significant restenosis of BMS and PF-PCS were mainly organising/organised thrombus. CONCLUSION: Organising and/or organised thrombus attachment due to poor BTK runoff was the main cause of in stent restenosis of the swine femoral artery. FP-PES demonstrated the least percent area stenosis, suggesting the importance the antithrombotic effect of polymer.

To perform intravascular ultrasound (IVUS)-based real-time 3-dimensional wiring in chronic total occlusion percutaneous coronary intervention, we devised a tip detection method and developed AnteOwl WR (AO)-IVUS, which is an upgraded version of Navifocus WR (Navi)-IVUS with an added pull back transducer system. We compared the procedural outcomes of AO-IVUS-based 3-dimensional wiring using the tip detection method (n = 30) and Navi-IVUS-based conventional wiring (n = 17) in chronic total occlusion percutaneous coronary intervention. The success rate of IVUS-guided wiring was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (93% vs 59% of cases, respectively; P = 0.007). In cases of successful IVUS-guided wiring, the IVUS-guided wiring time was markedly improved in the AO-IVUS group compared with the Navi-IVUS group (9 ± 8 minutes vs 24 ± 26 minutes, respectively; P = 0.001). There were 2 successful cases of tip detection-antegrade dissection and re-entry in the AO-IVUS group.

BACKGROUND: Cancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST). METHODS: From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases, n = 253; controls, n = 1012) with cancer-related information available. RESULTS: The prevalence of patients with cancer history was higher (12.3% vs. 8.5%, p = 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%, p = 0.021; 3.2% vs. 1.3%, p = 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92-8.55, p = 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65, p = 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00, p = 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51, p = 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40, p = 0.023). CONCLUSION: A post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.

Recent studies showed that preoperative functional assessment with fractional flow reserve (FFR) could predict a long-term patency of arterial bypass grafts in patients with coronary artery bypass grafting (CABG). Quantitative flow ratio (QFR) is a novel angiography-based approach to estimate FFR. This study aimed to investigate whether preoperative QFR could discriminate arterial bypass function at 1 year after surgery. The PRIDE-METAL registry was a prospective, multicenter observational study that enrolled 54 patients with multivessel coronary artery disease. By protocol, left coronary stenoses were revascularized by CABG with arterial grafts, whereas right coronary stenoses were treated with coronary stenting. Follow-up angiography at 1 year after surgery was scheduled to assess arterial graft patency. QFR was performed using index angiography by certified analysts, blinded to bypass graft function. The primary end point of this sub-study was the discriminative ability of QFR for arterial graft function, as assessed by receiver-operating characteristic curve. Among 54 patients enrolled in the PRIDE-METAL registry, index and follow-up angiography was available in 41 patients with 97 anastomoses. QFR were analyzed in 35 patients (71 anastomoses) with an analyzability of 85.5% (71/83). Five bypass grafts were found to be non-functional at 1 year. The diagnostic performance of QFR was substantial (area under the curve: 0.89; 95% confidence interval: 0.83 to 0.96) with an optimal cutoff of 0.76 to predict functionality of bypass grafts. Preoperative QFR is highly discriminative for predicting postoperative arterial graft function.Trial registration: Clinical.gov reference: NCT02894255.

BACKGROUND: Excimer laser is used to treat coronary artery disease, especially in case of lesions with thrombus and in-stent restenosis (ISR). However, there are no in vivo preclinical studies that have evaluated the pathological reactions of the vessel wall after excimer laser ablation. METHODS: Bare-metal stents were placed in the external iliac arteries of six healthy rabbits. Twenty-eight days later, excimer laser ablation was performed with low-power (45 (fluency)/25 (rate)) in one side, and high-power (60/40) in the opposite side, followed by optical coherence tomography (OCT) evaluation. Rabbits were sacrificed 15 min after the procedure, and histological assessment was performed. RESULTS: Morphometry analysis of OCT showed similar stent and lumen size between low-power and high-power group. Histological evaluation suggested endothelial cell loss, fibrin deposition, and tissue loss. The low-power group showed significantly less pathological changes compared with the high-power group: angle of endothelial cell loss, 32.4° vs. 191.7° (interquartile range, 8.8°-131.7° vs. 125.7°-279.5°; p < 0.01); fibrin deposition, 1.1° vs. 59.6° (0.0°-70.4° vs. 31.4°-178.4°; p = 0.03); and tissue loss 0.0° vs. 18.2° (0.0°-8.7° vs. 0.0°-42.7°; p = 0.03). CONCLUSIONS: The pathological changes in neointima were more prominent after high-power excimer laser ablation than after low-power excimer laser. To improve safety in clinical practice, understanding the pathological changes of tissues after excimer laser in lesions with ISR is essential.

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.

Background The aim of this study was to estimate the impact of respiratory and electrocardiogram (ECG)-gated FDG positron emission tomography (PET)/computed tomography (CT) on the diagnosis of cardiac sarcoidosis (CS). Methods and Results Imaging from thirty-one patients was acquired on a PET/CT scanner equipped with a respiratory- and ECG-gating system. Non-gated PET images and three kinds of gated PET/CT images were created from identical list-mode clinical PET data: respiratory-gated PET during expiration (EX), ECG-gated PET at end diastole (ED), and ECG-gated PET at end systole (ES). The maximum standardized uptake value (SUVmax) and cardiac metabolic volume (CMV) were measured, and the locations of FDG accumulation were analyzed using a polar map. The mean SUVmax of the subjects was significantly higher after application of either respiratory-gated or ECG-gated reconstruction. Conversely, the mean CMV was significantly lower following the application of respiratory-gated or ECG-gated reconstruction. The segment showing maximum accumulation was shifted to the adjacent segment in 25.8%, 38.7%, and 41.9% of cases in EX, ED, and ES images, respectively. Conclusion In FDG PET/CT scanning for the diagnosis of CS, gated scanning is likely to increase quantitative accuracy, but the effect depends on the location and synchronization method.

AIMS: In recent large trials, sacubitril/valsartan demonstrated favorable effects in patients with HF. However, many patients do not achieve the target dose of treatment. This study investigated the factors linked to up-titration of sacubitril/valsartan in patients with heart failure and preserved ejection fraction (HFpEF). METHODS: Using a multicenter retrospective database, 204 consecutive patients with HFpEF (left ventricular ejection fraction ≥ 40%) who were treated with sacubitril/valsartan between October 2020 and March 2022 were analyzed. Up-titration was defined as an increase in dosage above 24/26 mg BID beyond 12 weeks after the initiation of sacubitril/valsartan. RESULTS: Among the patients, 55% underwent up-titration, and 8% discontinued the drug. The baseline systolic blood pressure (SBP) was higher in patients with up-titration than in those with no up-titration; SBP values similar to that at baseline were observed between the 2 groups at 2 to 4 weeks and at 12 weeks after the commencement of sacubitril/valsartan treatment. The majority of those who discontinued sacubitril/valsartan did so because of hypotension. The multivariable logistic regression model showed that a history of hypertension, history of atrial fibrillation, baseline SBP, and baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 were associated with sacubitril/valsartan up-titration. CONCLUSION: Approximately half of all patients did not undergo up-titration, and 8% of those with HFpEF discontinued the sacubitril/valsartan therapy. For aggressive up-titration and continuation of sacubitril/valsartan, patients with lower baseline SBP, renal dysfunction, absence of a history of hypertension, and presence of atrial fibrillation may require more careful monitoring.

AIM: Psychological distress is associated with poor prognosis in patients with cardiovascular disease (CVD). However, factors related to psychological distress in elderly patients with CVD is less understood. We aimed to investigate the rate of psychological distress in elderly patients with CVD in comparison with that of patients without CVD and to examine the clinical, socioeconomic, and lifestyle factors associated with this condition. METHODS AND RESULTS: Data from a nationwide population-based study in Japan of patients aged ≥ 60 years were extracted, and 1:1 propensity score matching was conducted of patients with and without CVD. Psychological distress was assessed using the K6 scale, on which a score ≥ 6 was defined as psychological distress. Of the 24,388 matched patients, the rate of psychological distress was significantly higher among patients with CVD compared to those without CVD (29.8% vs. 20.5%, p < 0.0001). The multivariate analysis revealed that female sex, comorbidities except hypertension, current smoking, daily sleep duration of < 6  h versus ≥ 8  h, home renter versus owner, retired status, having a walking disability, and lower monthly household expenditure were independently associated with psychological distress. Walking disability was observed in greatest association with psychological distress (odds ratio 2.69, 95% confidence interval 2.46-2.93). CONCLUSION: Elderly patients with CVD were more likely to have psychological distress compared to those without CVD. Multiple factors, including clinical, socioeconomic, and lifestyle variables, were associated with psychological distress. These analyses may help health care providers to identify high risk patients with psychological distress in a population of older adults with CVD.

Managing right-sided chronic heart failure (CHF) due to tricuspid regurgitation (TR) remains a clinical challenge. Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling decompensated HF. However, its effects on right-sided CHF caused by TR are unclear. We sought to clarify the effects of TLV in CHF patients complicated with TR. The cohort consisted of 33 CHF patients with moderate or severe TR and permanent atrial fibrillation, who required hospitalization for HF. We observed 19 patients treated with TLV plus conventional therapies (TLV group) and 14 patients with conventional therapies alone (conventional group). Clinical characteristics, echocardiographic parameters, and laboratory data were investigated. Baseline characteristics were similar between groups. In the TLV group, the severity of TR at admission was 73.7% moderate and 26.3% severe. In the conventional group, these percentages were 85.7% and 14.3%, respectively. During the follow-up, the severity of TR improved in the TLV group (trivial-mild: 52.6%; moderate: 36.8%; severe: 10.5%) (p < 0.01). However, it did not improve in the conventional group (trivial-mild: 21.4%; moderate: 50.0%; severe: 28.6%) (p = 0.08). The diameter of the tricuspid annulus (p < 0.01), basal (p = 0.02), and mid right ventricle (p = 0.04) was reduced at follow-up in the TLV group. Nevertheless, these parameters did not change in the conventional group. Serum creatinine levels were maintained (p = 0.74) in the TLV group, but deteriorated in the conventional group (p = 0.03). TLV reduced right ventricular dimensions and improved TR without deterioration of renal function. Thus, TLV may be a new drug for the treatment of CHF patients with TR.

In this updated expert consensus document, the methods for the quantitative measurement and morphological assessment of optical coherence tomography (OCT)/optical frequency domain imaging images (OFDI) are briefly summarized. The focus is on the clinical application and the clinical evidence of OCT/OFDI to guide percutaneous coronary interventions.

BACKGROUND: Cardiovascular disease and cancer share a number of risk factors and pathophysiologic mechanisms. Although risk management and early detection of cancer in patients with cardiovascular disease are important, preventive efforts in cardiology and oncology have been relatively disconnected. This study aimed to investigate the rate of cancer screening in a population of older adults with cardiovascular disease. METHODS: This study used data from the 2019 Comprehensive Survey of Living Conditions. Data on participants aged 60 years or older were extracted. The rate of cancer screening and cancer type were investigated between participants with and without cardiovascular disease. RESULTS: Of the 132,442 individuals, participants with cardiovascular disease had a significantly lower rate of cancer screening than those without cardiovascular disease [male: 4401 of 7972 participants (55.2%) vs. 33,744 of 52,106 participants (64.8%), p < 0.001; female: 2500 of 4984 participants (50.2%) vs. 41,319 of 67,380 participants (61.3%), p < 0.001]. The rate of cancer screening was significantly lower in participants with cardiovascular disease than in those without cardiovascular disease, regardless of cancer type, including gastric, colorectal, lung, breast, and gynecologic cancer screening. A history of cardiovascular disease was a negative factor for cancer screening (odds ratio 0.71, 95% confidence interval 0.67-0.74 in male participants; odds ratio 0.80, 95% confidence interval, 0.75-0.85 in female participants). CONCLUSIONS: The rate of cancer screening in elderly participants with cardiovascular disease was lower than that in participants without cardiovascular disease. Physicians should raise awareness regarding early cancer detection in patients with cardiovascular disease.

Pulmonary artery sarcoma (PAS) is considered a very rare tumor with a poor prognosis. We herein report two cases of PAS that were diagnosed by positron emission tomography (PET)/computed tomography (CT). In both cases, PET was an effective option for diagnosing tumors, and surgical resection was a valid treatment for these diseases. If a pulmonary artery tumor is suspected, PET/CT is useful for diagnosing PAS and very helpful for choosing the surgical treatment strategy.

OBJECTIVE: We investigated the effect of proximal optimization technique (POT) on coronary bifurcation stent failure (BSF) in cross-over stenting by comparing with the kissing balloon technique (KBT) in a multicenter randomized PROPOT trial. BACKGROUND: POT is recommended due to increased certainty for optimal stent expansion and side branch (SB) wiring. METHODS: We randomized 120 patients treated with crossover stenting into the POT group, which was followed by SB dilation (SBD), and the KBT group. Finally, 52 and 57 patients were analyzed by optical coherence tomography before SBD and at the final procedure, respectively. Composite BSF was defined as a maximal malapposition distance of >400 μm, or malapposed and SB-jailed strut rates of >5.95% and >21.4%, respectively. RESULTS: Composite BSF before SBD in the POT and KBT groups was observed in 29% and 26% of patients, respectively. In the POT group, differences in stent volumetric index between the proximal and distal bifurcation (odds ratio [OR] 60.35, 95% confidential interval [CI] 0.13-0.93, p = 0.036) and between the proximal bifurcation and bifurcation core (OR: 3.68, 95% CI: 1.01-13.40, p = 0.048) were identified as independent risk factors. Composite BSF at final in 27% and 32%, and unplanned additional procedures in 38% and 25% were observed, respectively. Composite BSF before SBD was a risk factor for the former (OR: 6.33, 95% CI: 1.10-36.50, p = 0.039) and the latter (OR: 6.43, 95% CI: 1.25-33.10, p = 0.026) in the POT group. CONCLUSION: POT did not result in a favorable trend in BSF. Insufficient expansion of the bifurcation core after POT was associated with BSF.

BACKGROUND: Direct oral anticoagulants (DOACs) have been used to prevent cardiogenic embolism in patients with atrial fibrillation (AF). No evidence has been established for the follow-up renal function evaluation intervals. We hypothesized that a proposed follow-up interval of renal function can be estimated by patient's baseline characteristics including creatinine clearance (CCr). METHODS: We conducted a single-center retrospective study at Kindai University Hospital from May 2011 to December 2017. Patients were screened and they were enrolled if baseline CCr of ≥50 mL/min. To provide a periodical synchronization for measurements of CCr in all patients, these were evaluated at four different time points (approximately at 3, 6, 9, and 12 months). Primary endpoint was defined as a CCr value of <50 mL/min during the follow-up period. We analyzed associations between the cumulative risk for renal endpoint and baseline characteristics by the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Renal endpoint was associated with age (95% CI: 0.07 to 0.21, p<0.01), body weight (95% CI: -0.09 to -0.01, p<0.01), CCr (95% CI: -0.18 to -0.07, p<0.01), and CHA2DS2-VASc score (95% CI: 0.14 to 0.63, p<0.01). Combining baseline CCr of <60 mL/min and other risk factors, acceptable intervals for 5% risk levels were 78 days (age ≥75 years old), 100 days (CHA2DS2-VASc score of> 4 points), and 90 days (body weight <60kg), respectively. Under conditions of baseline CCr of <60 mL/min, age ≥75 years old, CHA2DS2-VASc score of> 4 points, or body weight <60 kg, an increased risk of renal endpoints is 4.85, 3.29, 1.24, 2.44 fold, respectively. CONCLUSIONS: We propose a risk-stratified follow-up interval for renal evaluation in patients with AF and DOACs therapy according to a combination of baseline CCr and other risk factors.

[This corrects the article DOI: 10.1253/circrep.CR-21-0084.].

INTRODUCTION: The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is uncertain. For patients with non-AF, many trials are now evaluating short 1-month dual antiplatelet therapy. In patients with AF undergoing PCI, in contrast, short dual therapy (P2Y12 inhibitor +direct oral anticoagulant (DOAC)) has not yet been evaluated. METHODS AND ANALYSIS: The OPTIMA-AF trial (OPTIMAl antiplatelet therapy in combination with direct oral anticoagulants in patients with non-valvular Atrial Fibrillation undergoing percutaneous coronary intervention with everolimus-eluting stent) is an investigator-initiated, open-label, nationwide, multicentre, prospective, randomised controlled trial. The primary objective is to compare the efficacy and safety of short dual therapy (1-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) against long dual therapy (12-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) in the treatment of AF subjects undergoing PCI. The primary efficacy endpoint is a composite of death or thromboembolic events (myocardial infarction, definite stent thrombosis, stroke or systemic embolism) at 365 days; and the primary safety endpoint is bleeding (International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding) at 365 days. This trial is intended to show the non-inferiority of short dual therapy versus long dual therapy in terms of the primary efficacy endpoint and show superiority in terms of the primary safety endpoint. A total of 1090 subjects will be randomised in a 1:1 ratio at approximately 60 sites. ETHICS AND DISSEMINATION: This study received approval from the Certified Review Board of Osaka University (a certified research ethics committee by the Japanese Clinical Research Act). The findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials: jRCTs051190053; Pre-results.

AIMS: To investigate the ability of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and ARC-HBR score to predict 2-year bleeding and mortality in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: We enrolled 2514 patients who underwent successful TAVR during 2013-17. In this study, we used the ARC-HBR score for further HBR-risk stratification, and the ARC-HBR score was calculated as follows: each major criterion was 2 points and each minor criterion was 1 point. The impact of the ARC-HBR criteria and increasing ARC-HBR score on the incidence of moderate/severe bleeding events, mortality, and ischaemic stroke in the first 2 years were evaluated. We used survival classification and regression tree (CART) analysis for 2-year moderate or severe bleeding events, and patients were statistically classified into HBR low- (ARC-HBR score ≤1), intermediate- (ARC-HBR score = 2-4), or high-risk (ARC-HBR score ≥5) groups, and 91.4% were at HBR (ARC-HBR score ≥2). The rates of 2-year moderate/severe bleeding events and all-cause mortality were higher in the ARC-HBR group and highest in the HBR high-risk group. An increased HBR score was significantly associated with moderate/severe bleeding events [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.07-1.31; P = 0.001] and all-cause mortality (adjusted HR 1.24, 95% CI 1.17-1.32; P < 0.001). CONCLUSIONS: The ARC-HBR criteria identify patients at HBR after TAVR; an increased ARC-HBR score is associated with 2-year moderate/severe bleeding events and mortality.

Background: Transesophageal echocardiography (TEE) is currently the gold standard technique for diagnosing left atrial appendage (LAA) thrombi. Cardiac computed tomography (CT) has been expected to become an alternative method to TEE; however, a reliable quantitative evaluation method has not been established. Methods and results: We enrolled 177 patients with persistent atrial fibrillation who underwent both cardiac CT and TEE before catheter ablation. The patients were classified into two groups according to the TEE results: the thrombus group (13 patients) and non-thrombus group (164 patients). The Hounsfield unit (HU) density at the proximal LAA (LAAp) and distal LAA (LAAd) was measured on cardiac CT images. The LAAd/LAAp HU ratio and standard deviation of HU density (HU-SD) at the LAAd were evaluated. We created an algorithm by decision tree analysis to predict LAA thrombus formation using the HU ratio and HU-SD. Definite absence of LAA thrombus (Category-I) was diagnosed for 139 patients by combining the first and second branching of the decision tree (Category-Ia: HU ratio of ≥0.26, Category-Ib: HU ratio of <0.26, HD-SD of ≥26.94). Definite presence of LAA thrombus (Category-Ⅱ) was diagnosed for 3 patients using the third branching of the decision tree (Category-Ⅱ: HU ratio of <0.26 and HU-SD of <13.85). Highly possibility of LAA thrombus (Category-III), but not definite, was diagnosed for the remaining 35 patients; therefore, these patients required diagnostic TEE. The diagnostic accuracy of this algorithm was 0.95. Conclusion: We have proposed a reliable algorithm to diagnose LAA thrombus formation using the HU ratio and HU-SD.

Background: Antiplatelet therapy following stent implantation in patients requiring oral anticoagulation (OAC) is controversial because triple therapy (i.e., dual antiplatelet therapy [DAPT] with OAC) is associated with a high risk of bleeding. Methods and Results: In this study, 21 rabbits were divided into 5 groups: prasugrel and warfarin (Prasugrel+OAC group); aspirin and warfarin (Aspirin+OAC group); prasugrel, aspirin, and warfarin group (Triple group); prasugrel and aspirin (Conventional DAPT group); and no medication (Control group). The treated groups were administered medication for 1 week. An arteriovenous shunt loop was established from the rabbit carotid artery to the jugular vein and 2 bare metal stents were deployed in a silicone tube. After 1 h of circulation, the volume of thrombi was evaluated quantitatively by measuring the amount of protein. Bleeding time was measured at the same time. The volume of the thrombus (amount of protein) around stent struts was lowest in the Triple group, followed by the Prasugrel+OAC and Conventional DAPT groups, and was highest in the Control group. Bleeding time was the longest in the Triple group, followed by the Aspirin+OAC, Prasugrel+OAC, Conventional DAPT, and Control groups. Conclusions: This study suggests that prasugrel with OAC may be a feasible antithrombotic regimen following stent implantation in patients who require OAC therapy.

BACKGROUND: Implantable cardioverter-defibrillator and cardiac resynchronization therapy using a defibrillator (ICD/CRT-D) are established means of reducing mortality due to ventricular arrhythmia. Although atrial fibrillation/flutter (AF) is the most common cardiac arrhythmia in patients with heart disease, the impact of AF on the prognosis of patients with ICD/CRT-D remains controversial. METHODS AND RESULTS: We analyzed data from the Nippon Storm Study, a prospective observational study of 1570 patients that was conducted at 48 Japanese ICD centers. We allocated 1549 participants to AF and non-AF groups, compared their clinical data at the time of enrollment, and monitored the incidences of mortality, hospitalization, and appropriate and inappropriate ICD/CRT-D therapy during a median 28 months. When the AF (n = 257, 16.6%) and non-AF-(n = 1292, 83.4%) groups were compared, the AF group was older (67.7 vs. 61.4 years; p<0.0001), and had lower left ventricular ejection fraction (38.0 ± 17.0% vs. 43.5 ± 18.9%; p<0.0001). During follow up, mortality was significantly higher in the AF than the non-AF group (p<0.0001). In multivariate analysis, AF was significantly associated with all-cause mortality [p = 0.013; hazard ratio (HR)=1.62]. Inappropriate ICD/CRT-D therapy occurred in 40/257 patients (15.6%) and AF was associated with a higher prevalence of inappropriate ICD/CRT-D therapy (p<0.0001; HR=2.25). CONCLUSION: The presence of AF at ICD/CRT-D implantation carries subsequent independent risks of 1.62-fold for death and 2.25-fold for inappropriate therapy.

OBJECTIVE: Therapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes. METHODS: We enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH. RESULTS: At baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1-126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure. CONCLUSIONS: The treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy.

BACKGROUND: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). METHODS: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. RESULTS: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012). CONCLUSIONS: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

AIMS: We aimed to investigate the differences in the prevalence, severity, and prognostic impact of malnutrition between patients with new-onset heart failure (HF) and worsening of chronic HF. METHODS AND RESULTS: In older (≥60 years) hospitalized patients with acute HF, malnutrition was assessed according to the Geriatric Nutritional Risk Index (GNRI). A score <92 was defined as malnutrition. The primary endpoint was a composite endpoint, including cardiac death or rehospitalization for HF. Among 210 patients, 37% (52/142) of patients with new-onset HF and 31% (21/68) of patients with worsening of chronic HF had malnutrition (P = 0.41). The GNRI classification was comparable between the two groups. Kaplan-Meier analysis revealed a significant difference in the incidence of the composite endpoint in patients with new-onset HF (GNRI < 92 vs. GNRI ≥ 92: 50% vs. 32%, P = 0.007), but not in patients with worsening of chronic HF (GNRI < 92 vs. GNRI ≥ 92: 67% vs. 68%, P = 0.91). The adjusted Cox proportional hazards model demonstrated that a GNRI of <92 was an independent prognostic factor for the composite endpoint in patients with new-onset HF only. CONCLUSIONS: Among older hospitalized patients with acute HF, the prevalence and severity of malnutrition were comparable between the two categories of patients. Malnutrition was an independent prognostic factor in patients with new-onset HF, while clinical prognosis was poor in patients with worsening of HF, irrespective of malnutrition. The prognostic impact of malnutrition differs between new-onset HF and worsening of chronic HF.

Background: The BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3-4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES). Methods: BP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density. Results: OFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (-0.6 ± 0.5 mm2 vs. 0.00 ± 0.4 mm2, p = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively; p < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3, p = 0.09). Conclusions: While both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.

OBJECTIVES: The primary objective of the current analysis was to assess the association between the clinical presentation at index procedure and mortality in patients with second-generation drug-eluting stent thrombosis (G2-ST). BACKGROUND: Patients with acute coronary syndrome (ACS) have a higher risk for stent thrombosis (ST) as compared with those with chronic coronary syndrome (CCS). However, clinical outcomes of patients with G2-ST after treatment for ACS and CCS remain poorly understood. METHODS: From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 313 patients with G2-ST. According to baseline clinical presentation, patients were divided into the 2 groups: the ACS and CCS groups (n = 147 and n = 166, respectively). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST events. Timing of ST, target lesion revascularization, and recurrent ST were also assessed. RESULTS: Early ST was more frequently observed in the ACS group (71.4% vs. 44.6%), while very late ST was less likely to occur in the ACS group than in the CCS group (11.6% vs. 30.7%). Cumulative 3-year incidence of all-cause death after the index ST events was comparable between the ACS and CCS groups (28.6% vs. 28.3%; hazard ratio: 1.14; 95% confidence interval: 0.75 to 1.73; p = 0.55). Compared with the CCS group, the ACS group showed higher incidences of target lesion revascularization and recurrent ST (23.8% vs. 17.2%; p = 0.06; and 9.9% vs. 1.4%; p = 0.001, respectively). CONCLUSIONS: Patients with G2-ST were associated with higher mortality irrespective of baseline clinical presentation.

Background Stent thrombosis (ST) after drug-eluting stent (DES) implantation remains a life-threatening complication. Recurrent ST (RST) is not a rare phenomenon, potentially contributing to high mortality after the index ST events. However, little evidence is available about the incidence, risk factors, and clinical outcomes of definite RST after DES thrombosis. Methods and Results From REAL-ST (Retrospective Multicenter Registry of ST After First- and Second- Generation DES Implantation), this study evaluated 595 patients with definite ST (first-generation DES thrombosis, n=314; second-generation DES thrombosis, n=281). During a median follow-up of 31 months, we identified 32 patients with definite RST after first-generation DES thrombosis (n=18) and second-generation DES thrombosis (n=15). Cumulative incidence of RST was 4.5% and 6.0% at 1 and 5 years, respectively, which did not significantly differ between first-generation DES thrombosis and second-generation DES thrombosis. Independent predictors of definite RST were early ST (hazard ratio [HR], 2.38; 95% CI, 1.06-5.35 [P=0.035]) and multivessel ST (HR, 3.47; 95% CI, 1.03-11.7 [P=0.044]). Definite RST was associated with a 2.8-fold increased risk of mortality (adjusted HR, 2.78; 95% CI, 1.35-5.73 [P=0.006]). Conclusions Cumulative incidence of definite RST did not significantly differ between first-generation DES thrombosis and second-generation DES thrombosis. Early ST and multivessel ST were risk factors of definite RST. Definite RST significantly increased mortality after DES thrombosis, highlighting the clinical importance of preventing RST to improve outcomes of patients with ST. Registration URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000025181.

BACKGROUND: Clinical implications of proximal optimisation technique (POT) for bifurcation lesions have not been investigated in a randomised controlled trial. AIMS: This study aimed to investigate whether proximal optimisation technique (POT) is superior in terms of stent apposition compared with the conventional kissing balloon technique (KBT) in real-life bifurcation lesions using optical coherence tomography (OCT). METHODS: A total of 120 patients from 15 centres were randomised into two groups: POT followed by side branch dilation or KBT. Finally, 57 and 58 patients in the POT and KBT groups, respectively, were analysed. OCT was performed at baseline, immediately after wire recrossing to the side branch, and at the final procedure. RESULTS: The primary endpoint was the rate of malapposed struts assessed by the final OCT. The rate of malapposed struts did not differ between the POT and KBT groups (in-stent proximal site: 10.4% vs. 7.7%, p=0.33; bifurcation core: 1.4% vs. 1.1%, p=0.67; core's distal edge: 6.2% vs. 5.3%, p=0.59). More additional treatments were required among the POT group (40.4% vs. 6.9%, p<0.01). At 1-year follow-up, only one patient in each group underwent target lesion revascularisation (2.0% vs. 1.9%). CONCLUSIONS: POT followed by side branch dilation did not show any advantages over conventional KBT in terms of stent apposition, however, the excellent mid-term clinical outcomes were observed in both strategies.

Background: Late catch-up phenomenon following stent implantation is a well-known complication. However, no report has evaluated thrombosis after 9 years with multi-modality and pathological evaluation. Case summary: A 71-year-old man with stable angina underwent elective percutaneous intervention of the left main coronary artery with implantation of a bare metal stent (BMS) 9 years ago. At the 9-year follow-up, coronary computed tomography (CCT) and coronary angiography (CAG) findings revealed a thrombus-like structure in the BMS slightly protruding into the sinus of Valsalva. Therefore, the previously prescribed double-antiplatelet therapy was replaced with an anticoagulant and clopidogrel, and a potent statin treatment was initiated. After the changes in drug treatment, follow-up examinations with CCT at 1 and 3 months suggested a decrease in the size of the thrombus; however, it appeared to increase after 6 months. Subsequently, the patient underwent surgical intervention. Pathological assessment of the explanted stent showed a proteoglycan-dominated extracellular matrix with few smooth muscle cells suggesting an organized thrombus. Discussion: It should be emphasized that multiple factors might be responsible for very late stent thrombosis, such as peri-stent strut chronic inflammation involving proteoglycans, stent protrusion, and poorly controlled type 2 diabetes mellitus, possibly further inducing inflammatory cells.

Background: Patients with implantable cardioverter defibrillator (ICD) use for primary prevention (primary prevention patients) of sudden cardiac death have lower incidence of appropriate ICD therapy (app-Tx) compared with those with ICD use for secondary prevention (secondary prevention patients). However, detail analysis of a second app-Tx after a first app-Tx is still lacking. Objective: This study aimed to compare the incidence of a second app-Tx in primary vs secondary prevention patients. Methods: We conducted sub-analysis of the Nippon Storm Study, which was a prospective, observational study involving 985 patients with structural heart disease (left ventricular ejection fraction ≤ 50%). Of these, we selected 251 patients (62 ± 14 years old, 82% men) who experienced at least one appropriate ICD therapy, and compared occurrence of a second app-Tx between primary (n = 116) and secondary (n = 135) prevention patients. Results: There was no significant difference in the incidence of a second app-Tx between primary and secondary prevention patients (the cumulative incidence for a second app-Tx was 59% at 1 year and 79% at 3 years in primary prevention patients vs the cumulative incidence for the second app-Tx was 59% at 1 year and 75% at 3 years in secondary prevention patients).Additionally, we evaluated the incidence of a second app-Tx according to basal structural disease (ischemic and non-ischemic cardiomyopathy) and found no significant difference between primary and secondary prevention patients. Conclusion: Once app-Tx occurs, primary prevention patients acquire the high risk of subsequent ventricular arrhythmias because there is a comparable incidence of a second app-Tx in secondary prevention patients.

Aims: The clinical impact of the type of atrial fibrillation (AF) has not been completely elucidated in non-ischemic cardiomyopathy (NICM). Although the structure and function of the left atrium (LA) provide prognostic information in patients with heart failure, the relationship of the AF type with LA structure and function in NICM is unclear. Methods: Consecutive patients with NICM who underwent cardiac magnetic resonance were evaluated and followed. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for major adverse cardiovascular events (MACE) related to the AF type, such as paroxysmal AF, chronic AF, and new-onset AF (NOAF). Results: Among 625 patients with NICM (mean age, 64.4 ± 14.2 years; women, 39.7%), 133 had a history of AF at baseline; of these, 60 had paroxysmal AF. Each baseline AF type was associated with higher LA volume and lower LA emptying fraction but not with an increased incidence of MACE (p = 0.245). New-onset AF developed in 5.9% of patients with sinus rhythm over a median follow-up period of 609 days, and maximum LA volume was a strong and independent predictor [p < 0.001, area under the ROC curve (AUC): 0.795]. Maximum LA volume was superior to LA emptying fraction and B-type natriuretic peptide (AUC: 0.683 and 0.680, respectively). The use of β-blocker and the age of the patient were associated with the incidence of NOAF (HR: 0.37, 95% CI: 0.16-0.84 and HR: 1.05, 95% CI: 1.01-1.09, respectively). Kaplan-Meier analysis showed that patients with NOAF had a higher incidence of MACE than those with sinus rhythm or baseline AF (p = 0.002). NOAF and LA emptying fraction were independent predictors of MACE (HR: 2.28, 95% CI: 1.20-3.97 and HR: 0.98, 95% CI: 0.96-0.99, respectively) after adjusting for age, sex, body mass index, and diagnosis. Conclusions: Paroxysmal and chronic AF in patients with NICM were not associated with an increased incidence of MACE despite their association with LA volume and function. NOAF was independently associated with poor prognosis. Higher maximum LA volume predicted the onset and lower LA emptying fraction was independently associated with poor prognosis.

BACKGROUND: Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS: Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

Background Dialysis is an independent risk factor for in-stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in-stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in-stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; P<0.01). On the other hand, the prevalence of an in-stent lipid-rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; P=0.03). In all cases with an in-stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post-stent implantation, an in-stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation. Conclusions In-stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.

Hemodialysis (HD) is associated with a high in-stent restenosis (ISR) rate even in the second-generation era. Drug-coated balloons (DCB) generally provide excellent clinical outcomes in patients with ISR lesions. Nonetheless, safety and efficacy of DCB for ISR lesions in HD patients are largely unknown. A total of 17 centers across Japan participated in this study. Patients were eligible for the study if ISR lesions were treated with DCB. Enrolled patients were divided into 2 groups (HD and non-HD groups). Angiographic, OCT, and clinical outcomes were compared between the HD and the non-HD groups. A total of 210 patients were enrolled (36 patients in the HD group, and 174 patients in the non-HD group). At 8 months, the binary restenosis rate was significantly higher (26.3% versus 11.3%, p = 0.02) and in-segment late loss was significantly higher (0.49 ± 0.61 mm versus 0.23 ± 0.33 mm, p = 0.02) in the HD group than the non-HD group. In the OCT analyses, change of minimum stent area between post- and pre-procedure was significantly smaller in the HD group compared to the non-HD group (0.08 ± 0.95 mm2 versus 0.68 ± 1.07 mm2, p = 0.004). Target vessel failure (TVF) rate at 2 years was significantly different between the 2 groups (25.0% in the HD group and 12.1% in the non-HD group, p = 0.04). In the multivariate analysis, HD was a significant predictor for TVF (Hazard ratio 5.81, 95% CI 1.28-26.4, p = 0.02). Clinical and angiographic outcomes following OCT-guided DCB treatment in ISR lesions were significantly worse in HD patients compared to non-HD patients.Clinical Trial Registration Information: https://clinicaltrials.gov/ct2/show/NCT02300454.

AIMS: Exogenous atrial natriuretic peptide (ANP) may be a logical treatment for heart failure (HF) patients with ANP deficiency. Lower ANP concentrations may result from HF with preserved ejection fraction (HFpEF), which also results in lower brain natriuretic peptide levels in HFpEF relative to HF with reduced ejection fraction (HFrEF), although clinical features regarding circulating ANP in HFpEF and HFrEF have not been fully investigated during acute HF. Here, we characterized the differential regulation of circulating ANP and the efficacy of exogenous ANP (carperitide) in patients with acute HF, especially HFpEF. METHODS AND RESULTS: Serum ANP levels before treatment and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 113 patients with acute HF who were divided into two groups: HFpEF vs. HFrEF. We mainly analysed the impact of baseline ANP levels and the presence of HFpEF on the diuretic effect of exogenous ANP. There was an inverse relationship between ANP levels and the diuretic effect of exogenous ANP (r2  = 0.19, P < 0.001). Patients with HFpEF had lower ANP levels (P < 0.001) and a greater diuretic effect of exogenous ANP than patients HFrEF (P < 0.001). HFpEF was an independent predictor of greater diuretic effect of exogenous ANP (P = 0.003), as with a lower baseline ANP level (P = 0.004). CONCLUSIONS: Patients with HFpEF might have an aspect of ANP deficiency and represent a promising therapeutic target for modulating circulating ANP.

Limited data exist on the comparison of clinical outcomes after first- and second-generation drug-eluting stent (DES) thrombosis. From the Retrospective Multicenter Registry of Stent Thrombosis (ST) After First- and Second-Generation DES Implantation registry, this study evaluated 655 ST patients (first-generation DES thrombosis [G1-ST], n = 342; second-generation DES thrombosis [G2-ST], n = 313). After propensity score matching, the final study population consisted of 159 matched patients. The primary end point was the cumulative 1-year incidence of mortality. The mortality after G2-ST at 1 year was similar to that after G1-ST (23.0% vs 22.9%, p = 0.76). Also, the G2-ST group showed a significantly lower rate of target lesion revascularization than the G1-ST group (9.7% vs 17.1%, p = 0.01). Risk factors of 1-year mortality included cardiogenic shock or arrest at the time of ST, multivessel ST, left ventricular ejection fraction ≤40%, advanced age, and final thrombolysis in myocardial infarction flow grade ≤2. In conclusion, patients with G2-ST showed a similar 1-year mortality to those with G1-ST, highlighting that ST remains a life-threatening complication in the second-generation DES era.

BACKGROUND: Although each 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to diagnose cardiac sarcoidosis (CS), active CS is still misdiagnosed. METHODS: Active CS, diagnosed by PET alone, was defined as focal or focal on diffuse FDG uptake pattern. In fusion PET/CMR imaging, using a regional analysis with AHA 17-segment model, the patients were categorized into four groups: (1) PET-/LGE-, (2) PET+/LGE-, (3) PET+/LGE+, and (4) PET-/LGE+. PET+/LGE+ was defined as active CS. RESULTS: 74 Patients with suspected CS were enrolled. Between PET alone and fusion PET/CMR imaging, 20 cases had mismatch evaluations of active CS, and most had diffuse or focal on diffuse FDG uptake pattern on PET alone imaging. 40 Patients fulfilled the 2016 the Japanese Circulation Society diagnostic criteria for CS. The interobserver diagnostic agreement was excellent (κ statistics 0.89) and the overall accuracy for diagnosing CS was 87.8% in fusion PET/CMR imaging, which were superior to those in PET alone imaging (0.57 and 82.4%, respectively). In a sub-analysis of diffuse and focal on diffuse patterns, the agreement (κ statistics 0.86) and overall accuracy (81.8%) in fusion PET/CMR imaging were still better. CONCLUSIONS: Fusion PET/CMR imaging with regional analysis offered reliable and accurate diagnosis of CS, covering low diagnostic area by FDG-PET alone.

Considering that transcatheter aortic valve replacement (TAVR) procedures have become less invasive, the duration for monitoring patient care after a successful TAVR can be reduced. Therefore, this study aimed to investigate the prognostic value of baseline echocardiographic parameters for non-delayed discharge in patients after TAVR. The study group included 154 consecutive patients (mean age: 84.4 ± 4.5 years; and 101 women) who underwent a TAVR. Comprehensive echocardiograms including both side indices of myocardial performance (IMP) and blood tests were obtained prior to the TAVR procedure. The median post-TAVR length of stay was 6 days while the mode and first quartile were both 4 days. Receiver operating characteristic curve analysis showed that the optimum cut-off value of the left-sided IMP in patients with a normal left ventricular ejection fraction (LVEF, ≥ 50%) (n = 124) for non-delayed discharge (≤ 4 days) was 0.34 with an area under the curve (AUC) value of 0.71563 and p value of < 0.0001, while the optimum cut-off value in patients with reduced LVEF (< 50%) (n = 30) was 0.47 with an AUC value of 0.77778 and p value of < 0.0120. An adjusted analysis indicated the negative left-sided IMP results as the only predictor for non-delayed discharge (p < 0.0001). Furthermore, the adjusted predictors for survival without early cardiovascular re-hospitalization within 6 months after TAVR were the positive left-sided IMP result, when the cut-off value of 0.52 was used, and the presence of elevated RAP of 8 to 15 mmHg. The early discharge policy should be carefully considered in high-risk populations, but the left-sided IMP may play a significant role in the pre-screening process.

OBJECTIVES: To evaluate the feasibility and efficacy of transcatheter aortic valve replacement (TAVR) in patients with small sinus of Valsalva (SOV). BACKGROUND: Patients with small SOV are considered unfavorable for TAVR since it carries risk of coronary obstruction after valve implantation. Therefore, these patients with small SOV were excluded from previous clinical trials. METHODS: Between February 2017 and February 2019, a total of 139 consecutive patients with severe aortic stenosis (AS) undergoing TAVR were prospectively enrolled in the Tokai Valve Registry. Patients with small SOV who were treated with smaller size of self-expandable transcatheter heart valve (THV) than expected by perimeter-based sizing were included in this study. Eleven patients (7.9%) were included. RESULTS: Mean age was 86.5 ± 3.8 years and median STS Score was 8.5% (interquartile range: 6.3-12.3%). Device success was accomplished in all patients and no coronary obstruction was observed. No moderate/severe paravalvular leakage, new onset conduction disturbance, and new permanent pacemaker implantation were noted. At 30-day follow-up, mean aortic valve gradient was 6.9 ± 1.7 mmHg and mean indexed aortic valve area was 0.95 ± 0.16 cm2 /m2 . Prosthetic valve performance was stable at 12-month follow-up. No severe prosthesis patient mismatch was documented at any time point. No in-hospital, 30-day, and 12-month mortality were observed. The median follow-up was 711 days (IQR: 547-803 days), and no patient was lost to follow-up. CONCLUSIONS: Our preliminary experience suggests favorable safety and efficacy of TAVR utilizing self-expandable THV with intentional down-sizing in patients with severe AS and small SOV in a mid-term follow-up.

Statin therapy has been shown to induce carotid atherosclerotic plaque regression and reduce the periprocedural ischemic complications of carotid artery stenting (CAS). This study assessed the safety and usefulness of pretreatment using a high-dose strong statin (HDSS) to reduce the periprocedural ischemic complications of CAS. We analyzed 117 carotid lesions treated by CAS that were evaluated with magnetic resonance imaging (MRI) within 48 h after the procedure. For 67 lesions, an HDSS (rosuvastatin 20 mg or atorvastatin 40 mg daily) were prescribed from at least 14 days before CAS to at least 14 days after procedure (HDSS group). Clinical and angiographic data, as well as in-hospital outcomes, of the HDSS group were retrospectively compared with 50 lesions with conventional treatment without an HDSS (non-HDSS group). There were no significant differences in the baseline clinical and procedural characteristics between the two groups. There was no side effect related to the HDSS. Stroke rates were similar between the two groups (3.0% in HDSS group vs 8.0% in non-HDSS group, p = 0.22). All were minor strokes. Compared to the non-HDSS group, the HDSS group had a lower frequency of new lesions on diffusion-weighted imaging (DWI) with MRI (25.4% vs 44.0%, p = 0.0345). New ipsilateral DWI-positive rate in the HDSS group was significantly lower than in the non-HDSS group (16.4% vs 34.0%, p = 0.0275). Nonipsilateral (contralateral or posterior circulation) DWI-positive rates were similar between the two groups (13.4% vs 20.0%, p = 0.34). Pretreatment with an HDSS might reduce the periprocedural ischemic complications of CAS.

BACKGROUND: Tolvaptan exerts potent diuretic effects in heart failure patients without hemodynamic instability. Nonetheless, its clinical efficacy for acute decompensated heart failure (ADHF) due to severe aortic stenosis (AS) remains unclear. This study aimed to evaluate the short-term effects of tolvaptan in ADHF patients with severe AS. METHODS: The LOw-Dose Tolvaptan (7.5 mg) in Decompensated Heart Failure Patients with Severe Aortic Stenosis (LOHAS) registry is a multicenter (7 centers) prospective registry that assessed the short-term effects of tolvaptan in subjects hospitalized for ADHF with severe AS. A total of 59 subjects were enrolled between September 2014 and December 2017. The primary endpoints were changes in body weight and fluid balance measured daily from baseline up to 4 days. RESULTS: The median [interquartile range] patient age and aortic valve area were 85.0 [81.0-89.0] years and 0.58 [0.42-0.74] cm2, respectively. Body weight continuously decreased, and fluid balance was maintained from baseline to day 4 (p < 0.001, p = 0.194, respectively). Median serum B-type natriuretic peptide concentration significantly decreased from 910.5 to 740.0 pg/mL by day 4 (p = 0.002). However, systolic blood pressure and heart rate were non-significantly changed (p = 0.250, p = 0.656, respectively). Hypernatremia (>150 mEq/L) and worsening renal function occurred in 2 (3.4%) and 4 (6.8%) patients, respectively. CONCLUSIONS: Short-term treatment with low-dose tolvaptan is safe and effective, providing stable hemodynamic parameters in patients with ADHF and severe AS.

Quantitative coronary angiography (QCA) remains to play an important role in clinical trials and post-marketing surveillance related to the safety and efficacy of new PCI devices. In this document, the current standard methodology of QCA is summarized. In addition, its history, recent development and future perspectives are also reviewed.

Clinical presentation of stent thrombosis (ST) and its sequela under contemporary practice have not been fully elucidated largely due to rare incidence of ST. We sought to assess the characteristics in patients with clinical presentation of ST and their in-hospital outcomes, utilizing nationwide registration system for percutaneous coronary interventions (J-PCI). The present study included acute coronary syndrome (ACS) patients undergoing PCI with clinical findings of definite ST from January 2014 to December 2016. Patients' characteristics, in-hospital mortality and its composite with periprocedural complications were evaluated. Full match comparison was performed. During the study period, 256,610 ACS patients (37.9% of total PCI cases) underwent PCI and 1,367 ST patients (1.9%) were identified from 73,241 ACS patients' records who had a history of previous PCI. Overall, patients with ST were younger but had higher incidence of previous myocardial infarction, compared with those without. In addition, ST patients had increased rate of crude in-hospital death (4.8% vs 1.1%, p <0.001). After full match comparison, the incidence of recurrent ST (post-PCI) was significantly higher in ST patients when compared with ACS patients presenting without ST (4.3% vs 0.9%, p <0.001). Despite younger age, patients with ST had significantly higher incidence of in-hospital mortality and cardiovascular complications, including recurrent ST, compared with those without.

BACKGROUND: Stent thrombosis (ST) remains a severe complication following stent implantation. We previously reported the risk factors for ST after 2nd-generation drug-eluting stent (DES) in the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation DES Implantation) registry.Methods and Results:In this subanalysis, we aimed to reveal the difference in ST between right coronary (RCA) and left (LCA) coronary arteries. A total of 307 patients with ST were divided into the RCA-ST group (n=93) and the LCA-ST group (n=214). Multivariate analysis revealed younger age (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.93-0.99, P=0.01), ostial lesion at the time of index percutaneous coronary intervention (OR 4.37, 95% CI 1.43-13.33, P=0.01), bifurcation lesion at the time of index PCI (OR 0.05, 95% CI 0.02-0.12, P<0.01), chronic total occlusion (CTO) lesion at the time of index PCI indication (OR 4.19, 95% CI 1.05-16.71, P=0.04), and use of prasugrel at the time of ST (OR 7.30, 95% CI 1.44-36.97, P=0.02) were significantly associated with RCA-ST. CONCLUSIONS: Younger age, ostial or CTO lesion, and use of prasugrel at the time of ST were prominent factors in RCA-ST, whereas bifurcation lesion was associated with LCA-ST. We should pay attention to the differences between RCA-ST and LCA-ST to prevent ST.

In this document, the methods for the quantitative measurement and morphological assessment of optical coherence tomography (OCT)/optical frequency domain imaging images (OFDI) are briefly summarized. The focus is on the clinical application of OCT/OFDI to guide percutaneous coronary interventions.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

BACKGROUND: In-stent restenosis (ISR) remains a problematic issue of coronary intervention. The non-slip element balloon (NSE) is a balloon catheter with 3 longitudinal nylon elements which are attached proximally and distally to the balloon component. The expectation is that this design of balloon is able to achieve a larger lumen area due to the elements, as well as reducing balloon slippage. We investigated whether NSE pre-dilatation improves angiographic outcomes compared to a high pressure non-compliant balloon pre-dilatation, followed by a drug-coating balloon (DCB) for treatment of ISR lesions with optical coherence tomographic imaging (OCT). METHODS: Patients were eligible for the study if one or more in-stent restenosis lesions were treated with a paclitaxel-coating balloon. Patients were randomized to NSE pre-dilatation (NSE group) or high pressure non-compliant balloon pre-dilatation (POBA group) in a 1:1 fashion in 17 hospitals. The primary endpoint was in-segment late loss [post minimal lumen diameter (MLD)-follow-up MLD] at 8 months. RESULTS: One hundred and five patients were allocated to each group. Balloon slippage (7.9% versus 22.9%, p=0.002) and geographical miss (6.9% versus 21.9%, p=0.002) were observed less in the NSE group compared to the POBA group. Acute gain was significantly larger in the NSE group (1.17±0.42mm versus 1.06±0.35mm, p=0.04), but post minimum stent lumen area analyzed by OCT was similar between the two groups (3.85±1.67mm2 versus 3.81±1.93mm2, p=0.64). At 8 months, average lesion length was significantly shorter than the POBA group (5.78±3.26mm versus 6.97±4.59mm, p=0.04), but average in-segment late loss was similar between the two groups (0.28±0.45mm versus 0.27±0.38mm, p=0.75). CONCLUSION: Eight-month angiographic outcomes were similar between NSE and non-compliant balloon pre-dilatation with DCB for treatment of ISR lesions. However, NSE pre-dilatation has advantages such as reduction of balloon slippage and geographical miss during the procedure.

Background The risk factors and long-term clinical outcomes of patients with definite stent thrombosis (ST) after second-generation drug-eluting stent (DES) implantation have not yet been adequately assessed. Methods and Results The REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation DES Implantation) included 313 definite ST of second-generation DES (early ST, n=179; late ST, n=66; very late ST, n=68). Four patients without definite ST of second-generation DES were identified as control patients for each ST case. Risk factors of definite ST were mostly different according to the timing of ST: ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina at presentation, current smoking, left ventricular ejection fraction <40%, prior percutaneous coronary intervention, stent overlap, severely calcified lesion, left main coronary artery lesion, proximal left anterior descending lesion, postdiameter stenosis ≥20%, for early ST; age <70 years, ST-segment-elevation myocardial infarction at presentation, hemodialysis, left ventricular ejection fraction <40%, in-stent restenosis, and severely calcified lesion for late ST; and proximal left anterior descending lesion and in-stent restenosis for very late ST. Cumulative 4-year incidence of death after the index ST events was significantly higher in the ST patients than control patients (33.0% versus 12.3%, P<0.001 for early ST versus control; 30.6% versus 14.2%, P<0.001 for late ST versus control; and 28.0% versus 13.0%, P<0.001 for very late ST versus control, respectively). Conclusions Risk factors of definite ST after second-generation DES implantation were mostly different according to the timing of ST. Definite ST patients showed unfavorable long-term clinical outcomes compared with those without definite ST. Clinical Trial Registration URL: https://www.umin.ac.jp . Unique identifier: UMIN000025181.

We previously reported safety and usefulness of transradial iliac artery stenting using 6 Fr guiding sheath. However, radial artery occlusion was a major limitation of this procedure. We analyzed the safety and utility of slender transradial iliac artery stenting using a 4.5 Fr guiding sheath to prevent radial artery occlusion. We performed transradial iliac artery stenting in left radial artery, using a 4.5 Fr sheath incorporating a shaft length of 110 cm, for 34 lesions in 29 patients. Transradial intervention was attempted at the discretion of the operator. Clinical data were analyzed retrospectively. Cases with scheduled multiple sheath insertions for a bidirectional approach were excluded. Twenty-three (79.3%) patients were male. Diabetes mellitus, hypertension, dyslipidemia, and smoking habit were present in 11 (37.9%), 27 (93.1%), 19 (65.5%), and 24 (82.8%) patients, respectively. Nine lesions (26.5%) were diagnosed as chronic total occlusion. All lesions were successfully treated using a total of 40 stents incorporating a 4.5 Fr radial access system. Ankle-brachial index (ABI) significantly improved from 0.68 ± 0.15 to 0.99 ± 0.17 (p < 0.0001) after the procedure. No patients had procedural or access site-related complications such as hematoma, major bleeding, blood transfusion, stroke, cholesterol embolism, aortic dissection, or arterial perforation. Radial artery occlusion was absent in all cases. ABI value was well maintained at 0.98 ± 0.13 at 1 year, and no target lesion revascularizations were reported. Slender transradial iliac artery stenting using a 4.5 Fr guiding sheath is safe, feasible, and less invasive, and shows no incidence of radial artery occlusion, in carefully selected patient populations.

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.

BACKGROUND: The Resolute Integrity coronary drug-eluting stent (DES), the next evolution of the Resolute DES, is designed with thinner stent struts and continuous sinusoidal technology to further enhance performance. This study evaluated the performance of the Resolute Integrity DES compared with the historical performance of Xience V. Methods and Results: We assessed the safety, efficacy, and deliverability of Resolute Integrity compared with the Xience DES, the prespecified historical control, in PROPEL, a large, real-world prospective, single-arm, open-label study. A total of 1,204 subjects were enrolled in PROPEL and treated with the Resolute Integrity DES at 76 sites in Japan. Lesion and procedural success rates were 100% and 99%, respectively. Patients were equally complex in the Resolute Integrity and Xience cohorts. At 1 year in the clinical-only cohort, the primary endpoint target lesion failure was 4.3% (34/800) in the Resolute Integrity cohort compared with 8.5% (97/1,142) in the Xience historical controls (P<0.001 for non-inferiority). Target vessel failure, major adverse cardiac events, target vessel myocardial infarction, and the composite cardiac death and target vessel myocardial infarction were all lower with Resolute Integrity compared with Xience, including in "high risk" patients. CONCLUSIONS: In the large, prospective, multicenter PROPEL trial, the performance of the Resolute Integrity DES was non-inferior to that of the benchmark Xience DES used as a historical comparator.

BACKGROUND: Optical coherence tomography (OCT) is increasingly used as an adjunct to coronary angiography for guiding percutaneous coronary intervention (PCI). The current consensus on PCI is that the large final stent area offers the best chance of a good late clinical outcome. Since OCT provides more accurate information about the coronary artery and implanted stents, OCT-guided stent implantation is expected to achieve greater stent expansion than angiography guidance alone. Therefore, we designed the COCOA (Comparison between Optical COherence tomography guidance and Angiography guidance in percutaneous coronary intervention) study to evaluate whether OCT-guided stent implantation would result in a minimum stent area greater than that achieved with angiography guidance alone. METHODS AND DESIGN: The COCOA study is a large-scale, multicenter, single country (Japan), prospective randomized controlled, open-label, parallel group, superiority study comparing OCT-guided PCI with angiography-guided PCI. The eligible patients (n=550) are randomly allocated in a 1:1 ratio to receive either OCT-guided PCI or angiography-guided PCI. PCI is performed using the everolimus-eluting stent in accordance with certain criteria of OCT or angiography for optimal stent implantation. Following the stent optimization guided by OCT or angiography alone, OCT is performed in both groups. The primary endpoint is minimum stent area at post-PCI with allocated imaging guidance. CONCLUSION: When completed, the COCOA study will contribute to define the clinical value of the OCT guidance in PCI.

BACKGROUND: The main drawback of current available drug coated balloons (DCB) is that a certain percentage of the coated drug is lost in the bloodstream during its delivery to the target lesion. We integrated the nanoparticle-mediated drug delivery technology and polydimethylsiloxane (PDMS) as a new excipient to facilitate an efficient drug delivery and uptake by endothelial cells. The present study aimed to evaluate the efficacy of the new DCB. METHOD AND RESULTS: The novel DCB were coated with 5.6mg of paclitaxel-incorporated nanoparticles using PDMS. The efficacy of the new DCB was examined in rabbit iliac stent model (n=12) and in the swine in-stent restenosis model (n=8) by quantitative coronary angiography (QCA) and optical coherence tomography (OCT). At 28days follow-up in the swine in-stent restenosis model, the area stenosis was significantly lower in DCB group as compared with that of the control group in OCT analysis (0.31±0.05 vs 0.49±0.06, p=0.04) though there was no significant differences observed in the rabbit iliac stent model in QCA and OCT analysis. CONCLUSION: The study results indicated that the paclitaxel-incorporated nanoparticle-coated balloon using PDMS has an inhibitory effect for the proliferation of smooth muscle cell in a swine coronary in-stent restenosis model.

The aim of this study is to evaluate differences in stent endothelial coverage among the second generation of drug-eluting stents. Incomplete stent coverage is one of the major causes of late stent thrombosis. Rabbits fed a normal diet received an everolimus (Xience Prime; EES) and a zotarolimus-eluting stent (Resolute Integrity; R-ZES) in each iliac artery, followed by sacrifice at 14 and 28 days after stent implantation. In addition, a group of atherosclerotic rabbits similarly received EES and R-ZES, and were sacrificed at 28 days. The extent of stent endothelial coverage was assessed by scanning electron microscopy. To evaluate endothelial coverage after bifurcation stenting, rabbits received EES and R-ZES placed with culotte stenting at the iliac bifurcation, followed by sacrifice at 14 and 28 days. In rabbits fed a normal diet, the percent uncovered strut area 14 days after stent implantation was significantly higher in R-ZES than in EES (10.1% (IQR 9.8-15.5) vs. 3.0% (IQR 1.5-9.7), p = 0.03), whereas it was not significantly different at 28-days (3.9% (IQR 0.8-10.3) vs. 1.0% (IQR 0.0-2.8), p = 0.2). In rabbits with induced atheroma, R-ZES also showed less endothelial coverage 28 days after stent implantation (5.3% (IQR 2.2-9.9) vs. 1.1% (IQR 0-6.2), p = 0.03). In the culotte stenting model, the percent uncovered strut area of the proximal overlapped segment was significantly higher in R-ZES at 14 days (15.8% (IQR 14.3-17.7) vs. 8.8% (IQR 8.3-9.8), p = 0.03) and 28 days (9.9% (IQR 4.1-13.9) vs. 2.5% (IQR 1.6-6.7), p = 0.04) after stent implantation. The carina area also showed a better coverage in EES compared with R-ZES. EES showed a better stent endothelial coverage compared with R-ZES after stent implantation in the early phase in normals, in arteries with lipid rich plaque, and in bifurcation stented sites.

OBJECTIVES: The authors sought to clarify how intravascular ultrasound (IVUS) and optical coherence tomography affect percutaneous coronary intervention (PCI) with current-generation drug-eluting stents in a pre-specified substudy of the OPINION (OPtical frequency domain imaging versus INtravascular ultrasound in percutaneous coronary interventiON) trial, a multicenter, prospective, randomized, noninferiority trial comparing optical frequency domain imaging (OFDI)-guided PCI with IVUS-guided PCI. BACKGROUND: The impact of these 2 imaging modalities in guiding PCI remains unknown. METHODS: Of 829 patients enrolled in the OPINION trial, 106 were included in the present imaging substudy. Their PCI was guided by either IVUS or OFDI, but all patients were imaged by both modalities after PCI and by OFDI at 8 months. Angiographic, OFDI, and IVUS images were analyzed by independent core laboratories, and statistical analysis was done independently by a dedicated institution. RESULTS: A total of 103 patients underwent either OFDI-guided (n = 54) or IVUS-guided (n = 49) PCI. Immediately after PCI, OFDI-guided PCI was associated with a smaller trend of minimum stent area (5.28 ± 1.65 mm2 vs. 6.12 ± 2.34 mm2; p = 0.088), fewer proximal stent-edge hematomas (p = 0.04), and fewer irregular protrusions (p = 0.014) than IVUS-guided PCI. At 8 months, the neointima area tended to be smaller in the OFDI-guided PCI group than in the IVUS-guided PCI group (0.56 ± 0.30 mm2 vs. 0.80 ± 0.65 mm2; p = 0.057), although the percentage of uncovered struts was significantly higher in the OFDI-guided PCI group than in the IVUS-guided PCI group (6.97 ± 7.03% vs. 4.67 ± 6.43%; p = 0.039). The minimum lumen area was comparable in both groups (p = 0.18). CONCLUSIONS: There were several differences in local findings between OFDI- and IVUS-guided PCI as expected given the different protocols for stent sizing in the 2 groups. The minimum lumen area at the 8-month follow-up was comparable, suggesting that OFDI- and IVUS-guided PCI are similarly feasible using the current-generation drug-eluting stents. (OPtical frequency domain imaging versus INtravascular ultrasound in percutaneous coronary interventiON; NCT01873222).

Although extracorporeal life support (ECLS) is utilized for acute hemodynamic collapse, clinical outcomes for such patients are uncertain. The present study examined 30-day clinical outcomes in patients treated with ECLS for acute hemodynamic collapse, and determined the factors associated with 30-day mortality in patients who required ECLS for cardiopulmonary arrest (CPA). A total of 200 patients, in whom emergency ECLS was utilized for acute hemodynamic collapse from 2006 to 2015, were analyzed retrospectively. The impact of CPA on all-cause 30-day death in the overall population was examined by multivariable logistic regression analysis; comparisons were made between 30-day survivors (n = 78) and non-survivors (n = 122). In addition, clinical factors associated with 30-day survival for patients in whom ECLS was utilized for CPA (n = 139) were examined. All-cause 30-day mortality in the overall study population was 61 % (122/200). CPA was the most common cause of ECLS requirement (70 %), and the factor associated strongest with death at 30-days (OR 3.31, 95 % CI 1.75-6.36, P < 0.01). Witnessed CPA with bystander cardiopulmonary resuscitation (CPR) (OR 4.33, 95 % CI 1.08-29.1, P = 0.04) and a less than 40 min interval between CPA and ECLS (OR 3.49, 95 % CI 1.39-9.02, P < 0.01) were suggested as factors associated with 30-day survival in CPA patients. CPA as a trigger of ECLS was a strong contributor to 30-day death in patients in whom emergency ECLS was utilized. However, witnessed CPA with bystander CPR and a less than 40 min interval from CPA to start of ECLS were suggested as factors associated with survival in these CPA patients.

Aims: Optical frequency domain imaging (OFDI) is a recently developed, light-based, high-resolution intravascular imaging technique. Intravascular ultrasound (IVUS) is a widely used, conventional imaging technique for guiding percutaneous coronary intervention (PCI). We aimed to demonstrate the non-inferiority of OFDI-guided PCI compared with IVUS-guided PCI in terms of clinical outcomes. Methods and results: We did a prospective, multicentre, randomized (ratio 1:1), active-controlled, non-inferiority study to compare head-to-head OFDI vs. IVUS in patients undergoing PCI with a second generation drug-eluting stent. The primary endpoint was target vessel failure defined as a composite of cardiac death, target-vessel related myocardial infarction, and ischaemia-driven target vessel revascularization until 12 months after the PCI. The major secondary endpoint was angiographic binary restenosis at 8 months. We randomly allocated 829 patients to receive OFDI-guided PCI (n = 414) or IVUS-guided PCI (n = 415). Target vessel failure occurred in 21 (5.2%) of 401 patients undergoing OFDI-guided PCI, and 19 (4.9%) of 390 patients undergoing IVUS-guided PCI, demonstrating non-inferiority of OFDI-guided PCI to IVUS-guided PCI (hazard ratio 1.07, upper limit of one-sided 95% confidence interval 1.80; Pnon-inferiority = 0.042). With 89.8% angiographic follow-up, the rate of binary restenosis was comparable between OFDI-guided PCI and IVUS-guided PCI (in-stent: 1.6% vs. 1.6%, P = 1.00; and in-segment: 6.2% vs. 6.0%, P = 1.00). Conclusion: The 12-month clinical outcome in patients undergoing OFDI-guided PCI was non-inferior to that of patients undergoing IVUS-guided PCI. Both OFDI-guided and IVUS-guided PCI yielded excellent angiographic and clinical results, with very low rates of 8-month angiographic binary restenosis and 12-month target vessel failure. Clinical registration: ClinicalTrials.gov, number NCT01873027.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) patients with diffuse ectatic coronary artery, extensive thrombi inhibit achievement of final successful revascularization of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after primary percutaneous coronary intervention. However, clinical and angiographic outcomes of such patients are uncertain. The present study examined clinical and angiographic outcomes in STEMI incorporating giant coronary artery with diffuse ectasia. METHODS: Seven hundred and forty-four STEMI patients undergoing primary percutaneous coronary intervention were surveyed retrospectively. Culprit lesions in giant coronary artery with diffuse ectasia (Ectatic group, n=39) were investigated. Percutaneous coronary intervention success rate and angiographic or clinical outcomes at 360 days were compared with those of the Non-ectatic group ( n=705). RESULTS: Angiographic percutaneous coronary intervention success rate was significantly lower in the Ectatic group due to lower achievement of final TIMI grade 3 flow (53.8% vs. 92.9%, p<0.0001; 53.8% vs. 93.5%, p<0.0001, respectively). In follow-up angiography, 86% of the Ectatic group showed angiographic improvement from TIMI grade 2 or less immediately after percutaneous coronary intervention to TIMI grade 3 flow at follow-up. In contrast, angiographic improvement was observed in only 25% of cases in the Non-ectatic group. All-cause 360-day mortality was significantly lower in the ectatic group (2.6% vs. 14.5%, p=0.0361, respectively). CONCLUSION: In patients with STEMI in giant coronary artery with diffuse ectasia, achievement of TIMI grade 3 flow was significantly reduced immediately after percutaneous coronary intervention. However, improvement of coronary flow up to TIMI grade 3 was not uncommon at follow-up angiogram. Patients had low mortality despite low TIMI grade 3 achievement immediately after primary percutaneous coronary intervention.

A reduction of low-density lipoprotein cholesterol (LDL-C) is important for the secondary prevention of coronary artery disease. We performed secondary prevention in 632 consecutive patients, including 315 with acute coronary syndrome, who underwent percutaneous coronary intervention according to current treat-to-target lipid-lowering guidelines to achieve LDL-C <100 mg/dL. We retrospectively analyzed 2-year all-cause mortality. The average LDL-C level was reduced from 114 ± 36 mg/dL at baseline to 94 ± 25 mg/dL at follow-up; 61 % of patients achieved the guideline target. Statin was not prescribed for 42 (6.6 %) patients, with reasons mainly due to a low baseline LDL-C level, however, renal failure, an older age, stable coronary artery disease and having a female gender were also related factors. At the end of follow-up (average 2.0 ± 0.9 years), 90 % of patients were on statins and showed a lower 2-year mortality rate than those not on statins (3.3 vs. 20.5 %, p < 0.001). In contrast, achieving LDL-C target levels did not impact mortality (4.9 vs. 4.8 %, p = 0.99). Propensity score matching analysis revealed statin use to be a predictor of better survival (p = 0.009) after adjusting for a baseline difference between statin and no statin groups. A multivariable Cox proportional hazard showed that age (HR = 1.12, 95 % CI 1.03-1.22) and statin use (HR = 0.14, 95 % CI 0.008-0.77) were predictors of survival. Statin use was a significant predictor of improved mortality rates under treat-to-target guidelines. However, it also highlighted a poor prognosis in patients without an indication for statins.

An important application of intravascular optical coherence tomography (IVOCT) for atherosclerotic tissue analysis is using it to estimate attenuation and backscatter coefficients. This work aims at exploring the potential of the attenuation coefficient, a proposed backscatter term, and image intensities in distinguishing different atherosclerotic tissue types with a robust implementation of depth-resolved (DR) approach. Therefore, the DR model is introduced to estimate the attenuation coefficient and further extended to estimate the backscatter-related term in IVOCT images, such that values can be estimated per pixel without predefining any delineation for the estimation. In order to exclude noisy regions with a weak signal, an automated algorithm is implemented to determine the cut-off border in IVOCT images. The attenuation coefficient, backscatter term, and the image intensity are further analyzed in regions of interest, which have been delineated referring to their pathology counterparts. Local statistical values were reported and their distributions were further compared with a two-sample t-test to evaluate the potential for distinguishing six types of tissues. Results show that the IVOCT intensity, DR attenuation coefficient, and backscatter term extracted with the reported implementation are complementary to each other on characterizing six tissue types: mixed, calcification, fibrous, lipid-rich, macrophages, and necrotic core.

The purpose of this study is to determine reduction of door-to-balloon (D2B) time using a single universal guiding catheter (Ikari-Left catheter) in transradial approach. In this procedure, we can skip a total of five steps compared with a conventional procedure (two catheter insertions, two catheter removals, and one catheter engagement). Reducing total ischemic time is important to achieving a better outcome in primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). We retrospectively compared 30 consecutive STEMI patients who underwent transradial primary PCI with a single guiding catheter (IL group) with 30 consecutive patients with conventional transradial primary PCI. Patients with cardiogenic shock, heart failure, or need for intra-aortic balloon pumping support before primary PCI were excluded. Baseline characteristics were not different between the two groups. The D2B time was significantly shorter in the IL group (55 ± 16 vs. 63 ± 17 min, respectively; p = 0.01). Puncture-to-balloon time was also significantly shorter in the IL group (15 ± 11 min vs. 25 ± 11 min, respectively; p = 0.001). The total number of diagnostic and guiding catheters was significantly less in IL group (1 (IQR 1-1) vs. 3 (IQR 3-3), respectively; p < 0.0001). Primary PCI with a single universal guiding catheter reduced D2B time by skipping several procedural steps, and reduced the total number of catheters needed. This technique could reduce patient mortality as well as total medical cost.

BACKGROUND: Collateral filling of chronic total occlusion (CTO) segments is considered to affect hemodynamic stability in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) with CTO, however its value as a prognostic indicator for mortality is uncertain. The present study examined the relationship between collateral filling of CTO segments and short-term mortality in patients with STEMI with a comorbid CTO lesion. METHODS: Among 829 STEMI patients who underwent primary PCI, 74 patients with CTO were identified. Collateral filling of their CTO segment was assessed by Rentrop grade (0; n=10, 1; n=13, 2; n=31, 3; n=20) in their initial angiogram and whether the origin of the feeding collateral donor artery was infarct-related artery (IRA) was evaluated using their final angiogram in primary PCI; IRA (n=26) and non-IRA group (n=48). The relationship between these classifications and 30-day all-cause mortality was examined retrospectively. RESULTS: The 30-day mortalities were 4.5% in single-vessel disease, 18.3% in multi-vessel disease (MVD) without CTO and 25.7% in MVD with CTO. Mortality of MVD with CTO reduced with increasing Rentrop grade from 0 to 3 (80.0%, 30.8%, 19.4%, and 5.0%, respectively). IRA was associated with a significant higher mortality than those of non-IRA (50.0% vs. 12.5%, P=0.0004). Low Rentrop grade 0 or 1 was extracted as an independent predictor of 30-day death (HR 3.28, 95% CI 1.20-9.96, P=0.0203). CONCLUSIONS: Poor collateral filling of the CTO segment assessed by Rentrop grade was an independent angiographic predictor for 30-day death in patients with STEMI combined with CTO.

A 56-year-old woman was diagnosed as atrial septal defect (ASD) with pulmonary hypertension; pulmonary blood flow/systemic blood flow (Qp/Qs) of 2.3, pulmonary artery pressure (PAP) of 71/23(39) mmHg and diastolic dysfunction of left ventricle. PAP was improved after medical therapy; therefore, transcatheter ASD closure was performed. Seven days later, left-sided heart failure occurred, however, the improvement of Qp/Qs (1.7) and PAP of 51/21(32) was confirmed. Diuretic therapy was introduced which led to further decrease of PAP 40/12(25) and Qp/Qs (1.1). Because of gradual decrease of Qp/Qs, this patient appeared to be protected from acute pulmonary edema.

OBJECTIVES: Although the left main coronary artery (LMCA) is clinically the most important site, little is known about the longitudinal plaque distribution and composition in the significant LMCA disease. METHODS: Preprocedure virtual histology intravascular ultrasound data were analyzed in 120 patients with significant LMCA bifurcation lesions (angiographic diameter stenosis>50%) requiring revascularization. Plaque burden and percentage of necrotic core (%NC) at the minimal lumen area site and maximal %NC site were measured in four segments: proximal LMCA, distal LMCA, left anterior descending (LAD) ostium, and proximal LAD. RESULTS: Angiographically, a significant LMCA and ostial LAD stenosis were observed in 89.2 and 81.7% of patients, respectively. At the minimal lumen area site, the proximal LAD segment showed the smallest lumen [3.5 mm (2.5-4.7), P<0.001] and the greatest plaque burden [73.2% (63.0-79.3), P<0.001] compared with the other segments. Also, there was a significant downward trend in the number of IVUS-defined lesions toward the proximal LMCA (P=0.001). At the maximal %NC site, the proximal LAD segment carried the largest necrotic core [32.7% (25.7-40.1), P<0.001] and the most frequent virtual histology thin-cap fibroatheroma (67.6%, P<0.001) among the segments, followed by the proximal LMCA [30.3% (22.3-40.0) and 32.9%, respectively]. Most of the plaques carried, at least, one slice of fibroatheroma in every segment; thus, fibroatheroma distributed in a continuous pattern from the proximal LAD to the proximal LMCA. CONCLUSION: In the significant LMCA bifurcation disease, the proximal LAD segment was found to have the smallest lumen, the largest plaque burden, the highest virtual histology thin-cap fibroatheroma rate, and thus presented the most vulnerable characteristics by virtual histology intravascular ultrasound.

BACKGROUND: Optical coherence tomography is becoming increasingly widespread as an adjunctive intravascular diagnostic technique in percutaneous coronary intervention (PCI), because of its ability to visualize coronary structures at high resolution. Several studies have reported that intravascular ultrasound (IVUS) guidance in PCI might be helpful to reduce subsequent stent thrombosis, restenosis, repeat revascularization, myocardial infarction, and cardiac death. The OPtical frequency domain imaging vs. INtravascular ultrasound in percutaneous coronary InterventiON (OPINION) trial is aimed at evaluating the impact of optical frequency domain imaging (OFDI) guidance in PCI on clinical outcomes compared with IVUS guidance. METHODS AND DESIGN: The OPINION trial is a multicenter, prospective, randomized, controlled, open-label, parallel group, non-inferiority trial in Japan. The eligible patients are randomly assigned to receive either OFDI-guided PCI or IVUS-guided PCI. PCI is performed using the biolimus-eluting stent in accordance with a certain criteria of OFDI and IVUS for optimal stent deployment. All patients will undergo a follow-up angiography at 8 months. The primary endpoint is target vessel failure composed of cardiac death, myocardial infarction attributed to the target vessel, and clinically-driven target vessel revascularization at 12 months. CONCLUSION: When completed, the OPINION trial will contribute to define the clinical value of the OFDI guidance in PCI.

BACKGROUND: Incomplete endothelialization is the primary substrate of late stent thrombosis; however, recent reports have revealed that abnormal vascular responses are also responsible for the occurrence of late stent failure. The aim of the current study was to assess vascular response following deployment of biodegradable polymer-based Synergy (Boston Scientific) and Nobori (Terumo) drug-eluting stents and the durable polymer-based Resolute Integrity stent (Medtronic) in an atherosclerotic rabbit iliac artery model. METHODS AND RESULTS: A total of 24 rabbits were fed an atherogenic diet, and then a balloon injury was used to induce atheroma formation. Synergy, Nobori, and Resolute Integrity stents were randomly implanted in iliac arteries. Animals were euthanized at 28 days for scanning electron microscopic evaluation and at 90 days for histological analysis. The percentage of uncovered strut area at 28 days was lowest with Synergy, followed by Resolute Integrity, and was significantly higher with Nobori stents (Synergy 1.1±2.2%, Resolute Integrity 2.0±3.9%, Nobori 4.6±3.0%; P<0.001). At 90 days, inflammation score was lowest for Synergy (0.27±0.45), followed by Nobori (0.62±0.59), and was highest for Resolute Integrity (0.89±0.46, P<0.001). Foamy macrophage infiltration within neointima (ie, neoatherosclerosis) was significantly less with Synergy (0.62±0.82) compared with Nobori (0.85±0.74) and Resolute Integrity (1.39±1.32; P=0.034). CONCLUSIONS: The biodegradable polymer-coated thin-strut Synergy drug-eluting stent showed the fastest stent strut neointimal coverage and the lowest incidence of neoatherosclerosis in the current animal model.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD) have higher mortality, especially with comorbid chronic total occlusion (CTO). The origin of collateral flow to the CTO segment has not been studied in regard to short-term mortality. This study examined the impact of collateral feeding donor arteries from an infarct-related artery (IRA) or non-IRA to the comorbid CTO segment in regard to STEMI short-term mortality. METHODS: Data from 760 consecutive STEMI patients who underwent primary percutaneous coronary intervention were obtained retrospectively from medical records. The number of vessels involved and origin of the collateral feeding donor artery were evaluated using angiograms from the primary percutaneous coronary intervention. The study population was divided into patients with: single-vessel disease (SVD) (n=483), MVD without CTO (n=208), and MVD with CTO (n=64). All CTO segments had collateral flow from an IRA (n=23) or non-IRA (n=46). All-cause mortality (30-day) was analyzed. RESULTS: Compared to SVD and MVD without CTO, MVD with comorbid CTO had a higher mortality (5.4% vs. 15.9% vs. 24.6%, P<0.0001, respectively). Of patients with CTO, those with collateral flow from the IRA had significantly higher mortality than the non-IRA group (52.2% vs. 10.9%, P<0.0001). Collateral flow from the IRA was extracted as an independent predictor associated with 30-day all-cause mortality using a multivariate Cox proportional hazards model (hazard ratio 4.71, 95% confidence interval 1.60-14.2, P=0.0005). CONCLUSIONS: The origin of the collateral donor artery from the IRA had an impact on short-term mortality in STEMI patients with comorbid CTO lesions.

AIMS: The purpose of this study was to determine the diagnostic ability of optical frequency domain imaging (OFDI) to carry out quantitative and qualitative evaluation of coronary calcification in comparing with ex vivo human autopsy heart specimens. METHODS: Analysis was carried out in 25 coronary artery specimen obtained from 16 cadavers that were imaged ex-vivo imaging by OFDI and intravascular ultrasound (IVUS). Of 235 cross-sections obtained for histologic evaluation, 149 were classified as showing calcified plaques, and in this group a comparison between histology versus co-registered images by OFDI and IVUS was performed. RESULTS: Maximum thickness of calcification measured by OFDI was well correlated with histology (rs = 0.70, p < 0.0001) whereas IVUS was not useful for quantitative analysis because of the presence of acoustic shadows occurring behind calcifications. Furthermore qualitative evaluation could be carried out using OFDI, for calcifications with vague or invisible outer borders by OFDI had lipid contents (lipid pool or histologic necrotic core) more frequently as compared to those with a clear outer border (79% vs. 24%, p < 0.0001). We also found that calcified nodules, a well-recognized thrombogenic substrate, demonstrated atypical appearance in OFDI, showing irregular surfaces with high attenuation. CONCLUSION: OFDI demonstrated a greater ability than IVUS to provide quantitative and qualitative evaluation of coronary arterial calcification. Precise recognition of calcified plaque morphology by OFDI may serve to determine the treatment strategy of patients having atherosclerotic coronary disease.

OBJECTIVES: To evaluate transradial intervention (TRI) for chronic total occlusion (CTO). BACKGROUND: Although TRI has been applied to more complex lesions in percutaneous coronary intervention, efficacy and feasibility of TRI versus transfemoral intervention (TFI) for CTO have not yet been determined. METHODS: We retrospectively analyzed 207 CTO lesions in 195 patients in a single center between January 2008 and December 2011. Patients were divided into four groups according to procedures: TRI (135 lesions in 124 patients); TFI (40 lesions in 39 patients); TRI/TFI (20 lesions in 20 patients); and TFI/TFI (12 lesions in 12 patients). Antegrade approach was used in TRI and TFI, but antegrade plus retrograde approach was used in TRI/TFI and TFI/TFI. RESULTS: Although there were no differences in patient characteristics, complex CTO lesions such as blunt-type entry and retry lesions were frequently observed in the TFI/TFI group. Average sheath size was 5.7 Fr for TRI and 6.6 Fr for TFI. Fluoroscopy time was significantly longer for the antegrade plus retrograde approach. Procedure success rates were not statistically different: 82.2% in TRI, 72.5% in TFI, 75.0% in TRI/TFI, and 75.0% in TFI/TFI groups. There was no death, myocardial infarction, or stroke at 30 days in any groups. Two femoral cases and no radial cases had access-site complications. Access-site crossover from radial to femoral was conducted in 4 cases. CONCLUSION: More than one-half of CTO lesions can be treated with high success and low complication rates by TRI if the lesions are carefully selected.

Routine use of distal protection for ST-segment elevation myocardial infarction (STEMI) is not recommended. The purpose of this study was to analyze the impact of slow flow on mortality after STEMI, and the efficacy of adjunctive distal protection following primary thrombus aspiration. We retrospectively analyzed 414 STEMI patients who underwent primary PCI. Distal protection was used following primary thrombus aspiration only when the operator judged the patient to be at high risk of slow flow. Patients were divided into 3 groups: those receiving no thrombus aspiration (A- Group), thrombus aspiration without distal protection (A+/D- Group) or a combination of aspiration with distal protection (A+/D+ Group). Slow flow/no reflow was characterized as transient or persistent. The A-, A+/D-, and A+/D+ Groups consisted of 28.5 % (n = 118), 44.4 % (n = 184), and 27.1 % (n = 112) of patients, respectively. All-cause mortality at 180 days was 6.8 % without slow flow, 14.1 % with transient and 44.4 % with persistent slow flow (P < 0.0001), but was similar whether or not distal protection was used among these groups complicated without slow flow (A-, 8.7 %; A+/D-, 6.3 %; A+/D+, 4.3 %; P = 0.5854). However, in cases complicated with transient or persistent slow flow, distal protection reduced all-cause mortality to 38.5 % (A-), 23.3 % (A+/D-), and 10.8 % (A+/D+) at 180 days (P = 0.0114). Our data confirm that routine distal protection is not to be recommended. However, it is suggested that it could reduce mortality of patients with slow flow. Predicting slow flow accurately before PCI, however, remains a challenge.

BACKGROUND: Percutaneous coronary intervention (PCI) guided with fractional flow reserve (FFR) has been shown to improve clinical outcome. Although coronary angiography is the standard method for PCI guidance, the visual severity of stenosis is not always correlated with functional severity, suggesting that there are additional angiographic factors that affect functional ischemia. METHODS AND RESULTS: To evaluate angiographic predictors of positive FFR in stenotic lesions, angiographic characteristics of 260 consecutive patients (362 lesions) who underwent FFR testing from April 2009 to September 2012 were analyzed. A scoring system (STABLED score) using these predictors was developed and compared with quantitative coronary angiography (QCA). %Diameter stenosis >50% (OR, 8.43; P<0.0001), tandem lesion (OR, 4.00; P<0.0001), true bifurcation (OR, 2.42; P=0.028), lesion length >20 mm (OR, 5.40; P=0.0002), and distance from ostium <20 mm (OR, 1.94; P=0.028) were determined as independent predictors of positive FFR. Area under the ROC curve for probability of positive FFR using the STABLED score (Stenosis 2 points, TAndem lesion 1 point, Bifurcation 1 point, LEsion length 1 point, Distance from ostium 1 point) was 0.85, higher than that for QCA stenosis alone (0.76). STABLED score ≥3 had 72.3% sensitivity and 83.6% specificity for predicting positive FFR, and PPV was 76.7%. CONCLUSIONS: Specific angiographic features are applicable for predicting functional ischemia. STABLED score correlates well with FFR.

BACKGROUND: The aim of this study was to investigate the accuracy of optical frequency domain imaging (OFDI) in lipid-rich plaque detection and determine the causes of "misinterpretation," and evaluate whether these limitations can be overcome with intravascular ultrasound (IVUS) using ex-vivo human coronaries. METHODS AND RESULTS: The OFDI images and corresponding 218 histological segments were evaluated. Segments with a poor signal and diffuse borders on OFDI, classified as lipid-rich plaques, were compared with the histological segments and IVUS images. Using histological images as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI for the detection of lipid-rich plaques were 93%, 93%, 85%, and 97%, respectively. The causes of false-positive diagnosis of lipid-rich plaque (11 segments) were superficial macrophage infiltration causing signal attenuation (8/11 segments, 73%) and tangential signal dropout of light (3/11 segments, 27%), whereas the cause of false-negative diagnosis was thickening of the fibrous cap (5 segments, 100%). Simultaneous IVUS helped to correct the misinterpretation of OFDI results and improved the diagnostic accuracy; the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI with adjunct use of IVUS were 96%, 99%, 99%, and 98%, respectively. CONCLUSIONS: OFDI occasionally over- or underestimates the existence of lipid-rich plaques, which may be overcome with adjunctive usage of IVUS.

AIMS: Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.

BACKGROUND: Preclinical evaluation of the vascular response of drug-eluting stents is limited especially in the setting of diabetes mellitus preventing the evaluation of changes in drug-eluting stent design and eluted drugs after clinical use. METHODS AND RESULTS: Cultured human aortic endothelial cells were used to assess the differences between sirolimus and its analog, everolimus, in the setting of hyperglycemia on various cellular functions necessary for endothelial recovery. A diabetic rabbit model of iliac artery stenting was used to compare histological and morphometric characteristics of the vascular response to everolimus-eluting, sirolimus-eluting, and bare metal stent placement. Under hyperglycemic conditions, sirolimus impaired human aortic endothelial cell barrier function, migration, and proliferation to a greater degree compared with everolimus. In our in vivo model of diabetes mellitus, endothelialization at 28 days was significantly lower and endothelial integrity was impaired in sirolimus-eluting stent compared with both everolimus-eluting and bare metal stents. Neointimal area, uncovered struts, and fibrin deposition were significantly higher in sirolimus-eluting compared with everolimus-eluting and bare metal stents. CONCLUSIONS: Use of everolimus-eluting stent results in improved vascular response in our preclinical models of diabetes mellitus.

BACKGROUND: Reducing total ischemic time is important in achieving better outcome in ST-segment elevation myocardial infarction (STEMI). Although the onset-to-door (OTD) time accounts for a large portion of the total ischemic time, factors affecting prolongation of the OTD time are not established. PURPOSE: The purpose of this study was to determine the impact of transport pathways on OTD time in patients with STEMI. METHODS AND SUBJECTS: We retrospectively studied 416 STEMI patients who were divided into 4 groups according to their transport pathways; Group 1 (n = 41): self-transportation to percutaneous coronary intervention (PCI) facility; Group 2 (n = 215): emergency medical service (EMS) transportation to PCI facility; Group 3 (n = 103): self-transportation to non-PCI facility; and Group 4 (n = 57): EMS transportation to non-PCI facility. OTD time was compared among the 4 groups. ESSENTIAL RESULTS: Median OTD time for all groups combined was 113 (63-228.8)min [Group 1, 145 (70-256.5); Group 2, 71 (49-108); Group 3, 260 (142-433); and Group 4, 184 (130-256)min]. OTD time for EMS users (Groups 2 and 4) was 138 min shorter than non-EMS users (Groups 1 and 3). Inter-hospital transportation (Groups 3 and 4) prolonged OTD by a median of 132 min compared with direct transportation to PCI facility (Groups 1 and 2). Older age, history of myocardial infarction, prior PCI, shock at onset, high Killip classification, and high GRACE Risk Score were significantly more frequent in EMS users. PRINCIPAL CONCLUSIONS: Self-transportation without EMS and inter-hospital transportation were significant factors causing prolongation of the OTD time. Approximately 35% of STEMI patients did not use EMS and 21% of patients were transported to non-PCI facilities even though they called EMS. Awareness in the community as well as among medical professionals to reduce total ischemic time of STEMI is necessary; this involves educating the general public and EMS crews.

OBJECTIVES: The aim of this study was to determine the in vivo longitudinal strength and conformability of various stent platforms following stent implantation in rabbit iliac arteries. BACKGROUND: Recently, longitudinal coronary stent deformation has been highlighted and bench tests have demonstrated differences in longitudinal strength among various stent platforms. However, this has not been investigated in an in vivo setting. This is of interest because there may be a trade-off between longitudinal strength and conformability. METHODS: We evaluated 4 types of commercially available stents: Multi-Link 8 (Abbott Vascular); Omega (Boston Scientific); Integrity (Medtronic); and Nobori (Terumo Corporation). To investigate the longitudinal strength, constant axial force was applied to the stent edge by a guiding catheter after deployment in a rabbit iliac artery. The amount of longitudinal stent deformation was calculated by measuring stent length. In order to evaluate conformability, stents were deployed crossing over the iliac bifurcation and the bifurcation angles were measured before and after stent implantation. If the change in the angle was small, the stent was considered to be more conformable. RESULTS: The Omega stent demonstrated significantly greater longitudinal compression compared with other stents (Omega, 17.4 ± 9.3%; Multi-Link 8, 2.8 ± 2.3%; Integrity, 2.8 ± 1.4%; Nobori, 3.8 ± 3.2%; P=.01), but Omega showed better conformability, as evidenced by the smallest percent change in the bifurcation angle (Omega, 12.7 ± 0.8%; Multi-Link 8, 25.7 ± 2.4%; Integrity, 28.3 ± 1.1%; Nobori, 28.1 ± 6.8%; P=.03). CONCLUSION: In this rabbit model, the Omega stent, which has the platform of the Element stent, showed less longitudinal strength but greater conformability compared with the other stent platforms.

OBJECTIVES: To compare clinical outcomes between transradial (TRI) and transfemoral intervention (TFI) in primary percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction (STEMI) with or without shock. BACKGROUND: TRI for STEMI has benefits in TRI high volume centers. However, TRI has not been reported for STEMI with shock even in such centers. METHODS: We retrospectively studied 425 STEMI patients who underwent primary PCI. Patients were divided into four groups according to approach site and presence of cardiogenic shock, including TRI without shock (TR group, n = 273), TRI with shock (TRS group, n = 38), TFI without shock (TF group, n = 71), and TFI with shock (TFS group, n = 43). RESULTS: PCI success rates were similar among the four groups. The TR group was superior to the TF group in terms of shorter cath lab to first device activation time, and lower access site complications, and 30-day mortality rates (1.1% vs. 11.3%, P < 0.001). In shock patients, cardiopulmonary arrest was commonly observed in both the TRS and TFS groups (42.1% and 51.2%, respectively). The TRS group showed a trend toward a shorter door to first device activation time compared to the TFS group and lower access site complications; however, 30-day mortality rate was 28.9% in TRS and 25.6% in TFS group (P = 0.7). CONCLUSIONS: In TRI high volume center, TRI for STEMI was safe and feasible as a default approach. TRI could be applied to severe shock patients with similar clinical outcome to TFI.

BACKGROUND: This study directly compared optical coherence tomography (OCT) and histopathology for the assessment of vascular response to first- and second-generation drug-eluting stents. METHODS AND RESULTS: Sirolimus-, everolimus-, and biolimus-eluting stents (SES, EES, and BES, respectively) were randomly implanted into the coronary arteries of 12 porcine. OCT was conducted after implantation: at 1, 3, and 6 months; histopathology was assessed at 3 and 6 months. At 1-month OCT, EES had the highest neointimal area (NA) and lowest neointimal unevenness score (NUS). At 6 months, NA and NUS were equivalent among the stent types. ∆NA from 1 to 6 months was lowest for EES, and ∆NA correlated with the histopathological inflammation score at 6 months, which was highest for SES (P<0.001). The mean signal intensity (MSI) and the attenuation were different for the stent types at 3 months, and were associated with inflammation score. Moderate diagnostic efficiency for measuring MSI was found, with an optimal cut-off of 6.88 predicting a high (≥grade 3) inflammation score. CONCLUSIONS: EES had the greatest uniformity and the least neointimal proliferation and were associated with less persistent inflammation. OCT provides accurate morphometric data; furthermore, quantitative measurement of the optical properties may help assess histological inflammation, which was more predominantly associated with SES than with EES and BES.

BACKGROUND: The purpose of the present study was to confirm the diagnostic accuracy of Global Registry of Acute Coronary Events (GRACE) risk score 1.0 (GRACE 1.0) and updated GRACE 1.0 (GRACE 2.0) for in-hospital and 360-day mortality in ST-elevation myocardial infarction (STEMI) in Japanese patients. GRACE 1.0 and GRACE 2.0 are the established predictive models in acute coronary syndrome, but their application to Japanese patients has not been fully verified. METHODS AND RESULTS: The present study retrospectively analyzed 412 consecutive STEMI patients who had undergone primary percutaneous coronary intervention from January 2006 to September 2011. All causes of death during hospitalization were examined to confirm the diagnostic accuracy of GRACE 1.0 on receiver operating characteristic (ROC) analysis. Similarly, all causes of death during the 360 days after hospitalization were analyzed to confirm the diagnostic accuracy of GRACE 2.0. The average GRACE 1.0 score was 175.8±50.9. In-hospital and 360-day mortality were 13.1% and 15.5%, respectively. Area under the ROC curve, which describes the diagnostic accuracy of the GRACE 1.0 predicted in-hospital mortality and the GRACE 2.0 predicted 360-day mortality, was as high as 0.95 and 0.92, respectively. CONCLUSIONS: Both GRACE 1.0 and GRACE 2.0 had a high diagnostic accuracy for prediction of in-hospital and 360-day mortality in Japanese STEMI patients.

Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar clinical outcomes. This study was aimed to clarify the differences in the angiographic findings of EES as compared to SES. Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. From February to July 2010, 3197 patients were randomly assigned to receive either EES or SES. Of these, angiographic sub-study enrolled 571 patients (EES 285 patients, SES 286 patients). Angiograms were assessed qualitatively and quantitatively at procedure and at 8-12 months in the independent core angiographic laboratory. Late loss of the proximal edges tended to be greater in the EES group than that in the SES group (0.12 ± 0.49 vs. 0.04 ± 0.43 mm, P = 0.05), although late loss in the other segments was similar between the 2 groups. Edge restenosis was mainly observed in EES group, whereas body restenosis was demonstrated in half of SES group. Stent fracture was observed only in the SES group (1.5 %), and peri-stent contrast staining (PSS) tended to be more frequently observed in the SES group than in the EES group (3.6 and 1.5 %, P = 0.18). Restenotic response in the proximal edge was more prominent in the EES group as compared to the SES group. Abnormal angiographic findings such as stent fracture and PSS tended to be more frequent in the SES group.

OBJECTIVES: This study was designed to evaluate the pharmacokinetic and vascular healing of a second-generation everolimus-eluting stent (EES) and slow-release zotarolimus-eluting stent (R-ZES). BACKGROUND: Second-generation DESs have alleviated the safety concerns of late stent thrombosis by addressing issues of polymer biocompatibility and stent design, and optimizing drug loads and release kinetics. No preclinical comparison study exists between these stents. METHODS: Rabbit iliac artery stent implantation was performed using Xience Prime EES and Resolute R-ZES. Histomorphometric evaluation was performed at 28 and 60 days after implantation in an induced atheroma model. Endothelial coverage and maturation were assessed by scanning electron microscopy and immuno-labeling at 14 and 28 days following deployment. For pharmacokinetic studies, arterial tissue and stents were retrieved at 3, 14, 28, and 90 days, and blood samples were obtained during the first 24 hours. RESULTS: Vascular remodeling (percent stenosis, neointimal thickness) was similar in arteries implanted with either stent group. At 28 days, inflammation was significantly less in the EES group as compared to the R-ZES group (inflammation score: 1.59 ± 0.52 vs 2.22 ± 0.69, respectively; P=.044), with no differences observed at 60 days. Endothelial coverage was similar between both groups; however, endothelial maturation above stent struts was significantly higher in the EES group vs R-ZES group at 28 days (33 ± 20% vs 22 ± 21%, respectively; P=.040). Arterial drug level concentrations were also shown to be significantly less in the EES group vs the R-ZES group (P<.0001). CONCLUSIONS: Overall, EES and R-ZES displayed similar remodeling properties with lower arterial drug levels observed in the EES group vs the R-ZES group, which may have led to more rapid endothelial maturation.

A 79-year-old woman presented with unexplained hypoxia that became exacerbated by an upright posture (platypnea-orthodeoxia syndrome). A (99m)Tc-macroaggregated albumin pulmonary perfusion scan revealed a right to left shunt of 25.5% in the supine position and 32.3% in the sitting position. A dynamic CT scan and a transoesophageal echocardiogram confirmed the presence of a shunt across an atrial septal defect (ASD). A percutaneous transcatheter closure of the defect significantly improved the patient's blood oxygenation levels when she was in the upright position. An ASD should therefore be included in the differential diagnosis of platypnea-orthodeoxia syndrome, regardless of the patient's age.

BACKGROUND: The impact of regional wall motion abnormality (RWMA) on the accuracy of heart failure with preserved ejection fraction (HFpEF) diagnosis using the E/e' ratio, which is a non-invasive parameter of left ventricular diastolic performance, is unknown. The purpose of this study was to elucidate the impact of RWMA of the lateral wall (RWMAlat) on the correlation between E/e' and invasive parameters of left ventricular diastolic performance. METHODS: Three hundred and eight consecutive patients undergoing tissue Doppler imaging and catheterization pressure examination were retrospectively analyzed. E/e' was calculated as the ratio of early diastolic transmitral flow velocity to mitral annular velocity at the lateral wall. Invasive parameters including left ventricular end-diastolic pressure (LVEDP) and isovolumetric relaxation time constant (τ) were assessed based on the left ventricular pressure study. Correlation coefficients between E/e' and these invasive parameters were analyzed and compared between cases with RWMAlat and without RWMA. RESULTS: LVEDP and τ correlated well with E/e' for all 308 patients (r = 0.51 and r = 0.65, respectively). Sixty-two patients had RWMA; the remaining 246 did not have RWMAlat. We confirmed that the presence of RWMAlat weakens both the correlations between E/e' and LVEDP (r = 0.574 vs. r = 0.381), and E/e' and τ (r = 0.729 vs. r = 0.461). CONCLUSIONS: Although E/e' correlates well with parameters of left ventricular diastolic performance assessed by invasive methods, the presence of RWMAlat worsens this correlation. In cases with RWMAlat, careful assessment is required for HFpEF diagnosis because the diagnostic value of the E/e' ratio could be decreased compared to patients without RWMAlat.

OBJECTIVES: To demonstrate safety and efficacy of new 6 Fr intra-aortic balloon pumping (IABP) system. BACKGROUND: Access-site complications have been reported to increase adverse events following PCI. Some reports have shown access-site complications in conventional 8-Fr compatible IABP system. The new 6 Fr IABP system may reduce the complication rate due to the smaller size. METHODS: We extracted medical records for patients who underwent elective percutaneous coronary intervention under prophylactic 6 Fr or 8 Fr IABP assistance from January 2006 to December 2009 at Tokai University School of Medicine. The clinical outcomes were compared between 6 Fr and 8 Fr or between transfemoral and transbrachial IABP. RESULTS: A total of 42 cases were extracted, including 20 cases using 6 Fr IABP (47.6%) and 22 cases using 8 Fr IABP (52.4%). The 6 Fr IABP included 15 cases of transbrachial approach (75.0%) and 5 cases of transfemoral approach (25.0%). All cases of 8 Fr IABP were via transfemoral approach. The bedrest time was clearly shorter in the 6 Fr IABP group (75.8 ± 139.8 minutes vs 360.0 ± 104.7 minutes in the 8 Fr IABP group; P<.001). Bedrest time and duration of hospitalization were shorter in the transbrachial IABP group (0.0 ± 0.0 minutes and 1.0 days [interquartile range, 1.0- 2.0 days] vs 288.0 ± 107.3 minutes and 5.0 days in the transfemoral group [interquartile range, 3.0-8.0]; P<.001). Access-site complications were 0% with the 6 Fr system, but 13.6% with the 8 Fr IABP system. CONCLUSIONS: This study demonstrated that the 6 Fr IABP system and its transbrachial application may be feasible because of lower complication rates.

Although, the first-generation drug eluting stents (DES) have significantly reduced rates of restenosis compared to bare metal stents (BMS), an increased risk of late stent thrombosis (LST) has emerged as a major concern. Pathologic studies of patients dying from late DES thrombosis demonstrates delayed arterial healing characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. However, recent thorough investigations revealed additional mechanisms of stent thrombosis such as hypersensitivity reaction, excessive fibrin deposit with malapposition, or neoatherosclerosis, which are associated with device-specific components and the majority of very late stent thrombosis is likely associated with these abnormal vascular responses. Therefore, although the incidence of stent thrombosis following DES implantation is similar in each period, the underlying mechanisms of this complication may vary. In the current review, the mechanisms of stent thrombosis in the DES era will be discussed using the data from autopsy studies that have been published.

The aim was to examine the efficacy of the simple technique that reduces tangling of the guidewires by utilizing wet gauze during percutaneous coronary intervention with multiple guidewires. We defined "Critical tangle of the guidewires" as occurring when it became impossible to insert balloon catheters into the bifurcation lesion due to tangling of the guidewires without withdrawing and reinserting one of the guidewires. We compared the rate of the critical tangle of the guidewires between the group taking no special tangle precaution ("NP Group"), and the group taking the tangle precaution with the wet gauze ("Gauze Group"). Eighty-four patients were enrolled in the study and randomly assigned to either NP Group (n = 43) or Gauze Group (n = 41). The kissing balloon technique success was 42/43 (97.7%) versus 40/41 (97.6%), in NP Group and Gauze Group, respectively. The rate of critical tangle of the guidewires was significantly lower in Gauze Group (27.9 vs. 7.3%, p = 0.014). The manipulation of several guidewires utilizing gauze method will be a useful technique for reducing tangle of the guidewires during the procedure of kissing balloon technique.

OBJECTIVES: This study sought to validate the sensitivity and specificity of the Academic Research Consortium's (ARC) classification of stent thrombosis. BACKGROUND: Classification of stent thrombosis according to ARC criteria has become widely accepted. The criteria have not been validated against an autopsy standard. METHODS: An autopsy registry of 139 subjects with prior coronary stenting underwent detailed histopathological analysis to assess for stent thrombosis. Based on clinical data only, cases were adjudicated according to ARC stent thrombosis criteria, including a proposed modification of the possible classification to include death beyond 30 days due only to sudden death or acute ischemia. RESULTS: Autopsy results confirmed 51 cases as positive and 88 as negative for stent thrombosis. Clinical adjudication classified 105 cases as definite (10), probable (31), or possible (64) ARC stent thrombosis. Specificity was high for definite (99%) and definite plus probable (83%) criteria, but sensitivity was poor at 18% and 51%, respectively. Including the possible cases improved sensitivity to 92% but reduced specificity to 34% (58 false positives). The modified possible criteria eliminated 13 false positive cases (specificity = 49%) and was the best approximation of a hypothetical gold standard in a sensitivity analysis if late death represented at least 20% of all stent thrombosis cases. CONCLUSIONS: In a selected autopsy sample, restricting ARC stent thrombosis to definite or definite plus probable criteria results in substantial under-reporting of confirmed cases. Inclusion of a modified possible classification may provide the best estimate of late and very late stent thrombosis rates.

OBJECTIVES: Human coronary bare-metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant duration >30 days were examined for the presence of neointimal atherosclerotic disease. BACKGROUND: Neointimal atherosclerotic change (neoatherosclerosis) after BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis after DES implantation has not been reported. METHODS: All available cases from the CVPath stent registry (n = 299 autopsies), which includes a total of 406 lesions-197 BMS, 209 DES (103 sirolimus-eluting stents [SES] and 106 paclitaxel-eluting stents [PES])-with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation. RESULTS: The incidence of neoatherosclerosis was significantly greater in DES lesions (31%) than BMS lesions (16%; p < 0.001). The median stent duration with neoatherosclerosis was shorter in DES than BMS (DES, 420 days [interquartile range [IQR]: 361 to 683 days]; BMS, 2,160 days [IQR: 1,800 to 2,880 days], p < 0.001). Unstable lesions characterized as thin-cap fibroatheromas or plaque rupture were more frequent in BMS (n = 7, 4%) than in DES (n = 3, 1%; p = 0.17), with relatively shorter implant durations for DES (1.5 ± 0.4 years) compared to BMS (6.1 ± 1.5 years). Independent determinants of neoatherosclerosis identified by multiple logistic regression included younger age (p < 0.001), longer implant durations (p < 0.001), SES usage (p < 0.001), PES usage (p = 0.001), and underlying unstable plaques (p = 0.004). CONCLUSIONS: Neoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events.

BACKGROUND: Although atherosclerotic models, especially in the rabbit, have existed for a long time, a comparative study of various drug-eluting stent (DES) implantations in atherosclerotic arteries have not been systematically studied. METHODS AND RESULTS: New Zealand White rabbits (n=44) with induced atheroma received bilateral iliac artery stents: bare metal stent (BMS) (Driver) or a stent eluting zotarolimus (ZES) (Endeavor), sirolimus (SES) (Cypher), or everolimus (EES) (Xience V). After 28 days, tissues were harvested for histomorphometric analyses, en face analysis of endothelial coverage, and expression of endothelial nitric oxide synthase (eNOS). Area measurements of external elastic lamina and stent area were similar. Neointimal area was significantly less in all DES versus BMS, which was least in SES and EES; similar trends were noted for cell proliferation. Uncovered struts were greater for SES and EES and least in BMS, whereas ZES were in between and associated with the least fibrin. Macrophages of the neointima were significantly less for all DES relative to BMS. Plaque calcification underneath stents, however, was significantly greater in SES and ZES than in BMS. Although endothelial coverage in between struts was comparable between BMS and DES, there was significantly greater expression of eNOS in BMS and ZES relative to EES and SES. CONCLUSIONS: The rabbit atherosclerotic model of stenting showed delayed healing and significantly greater reduction of neointima following implantation of SES and EES; however, delayed healing was less in ZES with greater neointima (but less than BMS), endothelial regrowth, and eNOS expression.

OBJECTIVES: The purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES). BACKGROUND: Recent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants. METHODS: The overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died ≥ 30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed. RESULTS: Both platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES. CONCLUSIONS: Differential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications.

Radiocontrast-induced nephropathy (CIN) is one of the most serious complications of percutaneous coronary interventions (PCI). The prevention of PCI-related CIN for chronic kidney disease (CKD) patients has not been established yet. The intravascular ultrasound (IVUS) is commonly used as an imaging device during PCI. We performed IVUS-guided PCI while only using fluoroscopic imaging and without administering any routine contrast dye injection during the procedures. All patients underwent a baseline coronary angiography prior to the elective PCI. During the PCI, all the following procedures were done with X-ray fluoroscopic imaging without or with a minimized contrast dye injection: the engagement of the guiding catheter, insertion of the coronary guidewire, insertion of the IVUS catheter, the stent deployment and the post-dilatation. The diameter and the length of the balloon and the stent were determined according to the pre-procedural IVUS findings, and the end point of the stent dilatation was also judged according to the acquired minimal cross-sectional area of the stent. Here we report our findings from two cases representative of IVUS-guided minimum contrast PCI in which the volumes of contrast dye during the procedure were 5 and 4 ml, respectively. No CIN occurred after either procedure. The IVUS-guided minimum contrast PCI could be a promising option for the prevention of CIN after PCI.

OBJECTIVES: Upper-limb arterial anomalies are sometimes encountered during transradial coronary procedures. These anomalies may contribute to procedural failure or to vascular complications, and are a major reason why many operators tend to avoid transradial procedures. We investigated the frequency of right upperlimb arterial anomalies using antegrade arteriography in patients undergoing transbrachial coronary angiography or intervention, and discuss the potential impact of these anomalies on the transradial procedure. METHODS: We prospectively studied 163 consecutive patients who underwent right transbrachial coronary angiography or intervention for the first time during the period from May 2007 to December 2007. Following the transbrachial procedure, we performed antegrade transbrachial arteriography of right upper-limb arteries in these patients and investigated the frequency and anatomy of arterial anomalies. RESULTS: A total of 40 upper-limb arterial anomalies were observed in 38 patients (23.3%). These included 8 abnormal origins (4.9%), 2 radio-ulnar loops (1.2%), 25 tortuosities (15.3%), 4 stenoses (2.5%) and 1 loop (0.6%). In patients with congenital lesions (8 patients; 4.9%), abnormal origin of the radial artery was the most common anomaly encountered, and in the acquired group (25 patients; 15.3%), tortuosity was the most common abnormality. CONCLUSION: Even with a 23.3% incidence of right upper-limb arterial abnormalities, 98.8% of patients were acceptable for transradial coronary intervention except for 1.2% of radio-ulnar loops.

BACKGROUND: Several studies have indicated that the clinical outcomes of sirolimus-eluting stents (SES) are significantly associated with longitudinal positioning of the stent relative to the underlying plaque distribution. METHODS AND RESULTS: Optimal SES landing was determined using unique stepwise intravascular ultrasound (IVUS) criteria, mainly targeting the sites with plaque burden <50% (plaque area/external elastic membrane area x100). To verify the criteria, (1) achievability and (2) actual impact on clinical and angiographic outcomes were assessed. A total of 162 consecutive patients with 180 lesions were enrolled and treated according to the IVUS criteria. Plaque burden at the proximal and distal margins was 41.4+/-13.6% (n=144) and 34.9+/-15.6% (n=170), respectively (within 3 mm of stent ends). The target was achieved in 72.3% of the proximal and 84.1% of the distal margin for the criteria. A strikingly low angiographic margin re-stenosis rate (2.7% of proximal and 1.4% of distal margin) and low target lesion revascularization rate (2.2%) were achieved. Receiver operator characteristic curve indicated that plaque burden was the strongest predictor of margin re-stenosis and its threshold (51.6%) was almost identical to that of the criteria. CONCLUSIONS: The proposed stepwise IVUS criteria mainly targeting plaque burden <50% are feasible and useful in the real-world practice of SES implantation.

BACKGROUND: We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. METHODS AND RESULTS: Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 microg sirolimus/mm] and full-dose sirolimus [Combo, 5 microg sirolimus/mm). These Combo stents and the Cypher stent (10 microg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50%total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173+/-0.088 mm) compared with Cypher (0.358+/-0.225 mm), LD-Combo (0.316+/-0.228 mm), and Xience V (0.305+/-0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). CONCLUSIONS: Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

OBJECTIVES: Using human pathologic specimens from the CVPath registry, we aimed to investigate the location of the atherosclerotic plaque at bifurcation in native coronary atherosclerotic lesions and to determine the responses at bifurcation after implantation of bare-metal stents (BMS) and drug-eluting stents (DES). BACKGROUND: Greater atherosclerotic plaque burden has been reported to occur at low-shear regions of bifurcation. METHODS: Twenty-six randomly selected human atherosclerotic nonstented coronary bifurcation lesions were examined longitudinally for plaque distribution in patients dying of severe coronary artery disease. Forty stented bifurcation lesions (21 BMS and 19 DES) were reviewed and analyzed by morphometry. RESULTS: In nonstented coronary bifurcations, the lateral wall showed significantly greater intima as well as necrotic core thickness than the flow divider. In the stented lesion, the frequency of late stent thrombosis was greater in the DES group (75%) than in the BMS group (36%), whereas restenosis was more frequent in the BMS group (33%) than in the DES group (5%). Neointimal formation was significantly less at the flow divider compared with the lateral wall in the DES group (0.07 mm [interquartile range (IQR) 0.03 to 0.15 mm] vs. 0.17 mm [IQR 0.09 to 0.23 mm]; p = 0.001), whereas this difference was not significant in the BMS group. Similarly, uncovered struts and fibrin deposition was significantly greater at the flow divider compared with the lateral wall in the DES group (uncovered: 40% [IQR 16% to 76%] vs. 0% [IQR 0% to 15%]; p = 0.001; fibrin: 60% [IQR 21% to 67%] vs. 17% [IQR 0% to 55%]; p = 0.01), but not in the BMS group. CONCLUSIONS: Plaque formation in native coronary bifurcations and neointimal growth after DES implantation was significantly less at the flow divider versus the lateral wall. A higher prevalence of late stent thrombosis in DES compared with BMS was associated with greater uncovered struts at flow divider sites, which is likely due to flow disturbances.

This study compares the effects of two polymers currently being marketed on commercially available drug-eluting stents, PVDF-HFP fluorinated copolymer (FP) and phosphorylcholine polymer (PC), on re-endothelialization, acute thrombogenicity, and monocyte adhesion and activity. Rabbit iliac arteries were implanted with cobalt-chromium stents coated with FP or PC polymer (without drug) and assessed for endothelialization at 14 days by confocal and scanning electron microscopy (SEM). Endothelialization was equivalent and near complete for FP and PC polymer-coated stents (>80% by SEM). Acute thrombogenicity was assessed in a Chandler loop model using porcine blood. Thrombus adherence was similar for both polymers as assessed by clot weight, thrombin-antithrombin III complex, and lactate dehydrogenase expression. In vitro cell adhesion assays were performed on FP and PC polymer-coated glass coupon surfaces using HUVECs, HCAECs, and THP-1 monocytes. The number of ECs adhered to FP and control surfaces were equivalent and significantly greater than on PC surfaces (p<0.05). There were no differences in THP-1 monocyte adhesion and cytokine (MCP-1, RANTES, IL-6, MIP-1alpha, MIP-1beta, G-CSF) expression. The data suggests that biological responses to both FP and PC polymer are similar, with no mechanistic indication that these polymers would be causative factors for delayed vessel healing in an acute timeframe.

OBJECTIVES: This study aimed to evaluate the accuracy of optical coherence tomography (OCT) in analyzing the neointimal response to several drug-eluting stent (DES) types by comparing OCT images acquired in vivo with corresponding histological specimens using a nondiseased porcine injury model. BACKGROUND: Optical coherence tomography is emerging as a promising endovascular imaging tool for the evaluation of neointimal response after DES implantation. METHODS: A total of 84 stents were implanted-22 ML Vision (Abbott Vascular, Santa Clara, California), 22 Xience V (Abbott Vascular), 20 Endeavor (Medtronic, Minneapolis, Minnesota), and 20 Taxus Liberté (Boston Scientific, Natick, Massachusetts) stents-in normal porcine coronary arteries and were harvested at 28 (n=42) and 90 (n=42) days, with the different stent types equally distributed between the 2 follow-up periods. At termination, morphometric evaluation using OCT imaging was performed in all stented arteries. Histological morphometric analysis was performed and correlated with OCT. RESULTS: A total of 622 OCT-histology matched frames acquired from all stent designs were analyzed. The luminal (13.7%) and stent (6.1%) areas were consistently larger by OCT compared with histology. The mean neointimal thickness was very similar between techniques (approximately 3.27% variation). There was a high correlation between OCT and histology for the evaluation of neointimal area (R2=0.804), luminal area (R2=0.825), and neointimal thickness (R2=0.789). Correlation for total stent area was poor (R2=0.352). Although the proportion of individual struts determined to be uncovered by OCT and histology was similar, there was significant variation in the estimation of strut coverage between OCT and histology when the neointimal thickness was between 20 and 80 microm. This variation converged for neointimal thicknesses between 80 and 100 microm. CONCLUSIONS: Subtle differences in neointimal formation induced by current DES can be reproducibly analyzed in vivo by OCT. However, OCT measurement of stent area seems to have less correlation with histology.

OBJECTIVES: In this study, we hypothesized that an antihuman-CD34 antibody immobilized on the surface of commercially available sirolimus-eluting stents (SES) could enhance re-endothelialization compared with SES alone. BACKGROUND: Previous experience with antihuman-CD34 antibody surface modified Genous stents (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent endothelialization in vivo. METHODS: In the phase 1 study, stents were deployed in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3 bare-metal stents) and overlapping stenting with various combinations (12 vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody coating was applied on commercially available SES (SES-anti-CD34, n = 7) and compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by scanning electron/confocal microscopy analysis. RESULTS: In phase 1, single stent implantation showed greatest endothelialization in GS (99%) and in bare-metal stent (99%) compared with SES (55%, p = 0.048). In overlapping stents, endothelialization at the overlapping zone was significantly greater in GS+GS (95 +/- 6%) and GS+SES (79 +/- 5%) compared with the SES+SES (36 +/- 14%) group (p = 0.007). In phase 2, SES-anti-CD34 resulted in increased endothelialization compared with SES alone at 3 days (SES-anti-CD34 36 +/- 26%; SES 7 +/- 3%; and GS 76 +/- 8%; p = 0.01), and 14 days (SES-anti-CD34 82 +/- 8%; SES 53 +/- 20%; and GS 98 +/- 2%; p = 0.009). CONCLUSIONS: Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.

AIMS: The histologic response to self-expanding stent implantation into advanced atherosclerotic lesions has not been systematically investigated. We tested the hypothesis of whether gradual expansion of advanced atherosclerotic plaques by self-expanding stents would be an appropriate method to seal atherosclerotic lesions without causing plaque disruption as is usually observed with balloon-expandable stents. METHODS AND RESULTS: Twelve New Zealand white rabbits were fed an atherogenic diet (1% cholesterol) followed by arterial denudation and injection of washed autologous erythrocytes. Nitinol self-expanding stents of two different stent designs and strengths (n=12 for SX and n=12 for Micro-SX) were implanted into the previously formed lesions within the abdominal aorta six weeks following injection of erythrocytes. Four weeks following stent implantation, animals were sacrificed, specimens harvested and processed for histology. Histomorphometry was performed on stented and adjacent non-stented regions. Atherosclerotic lesions were composed of foam cells, cholesterol clefts and necrotic plaque. While SX stents showed an unfavourable outcome with respect to vessel remodelling and the percentage of uncovered stent struts, Micro-SX stents had fewer uncovered stent struts, less positive remodelling and less plaque injury. CONCLUSIONS: Nitinol Micro-SX self-expanding stents might be a valuable approach to seal high risk atherosclerotic lesions.

OBJECTIVES: The aim of this study was to perform pathologic assessment on stent fracture. BACKGROUND: Clinically, stent fracture has been reported in 1% to 2% of patients after drug-eluting stent (DES) implantation. METHODS: High-contrast film-based radiographs of 177 consecutive lesions from the CVPath DES autopsy registry were reviewed. Stent fracture was graded as I (single-strut fracture), II (> or =2 struts), III (> or =2 struts with deformation), IV (with transection without gap), and V (with transection causing gap in stent segment). The incidence of adverse pathologic findings (thrombosis and restenosis) was assessed histologically. RESULTS: Stent fracture was documented in 51 lesions (29%; grade I = 10, II = 14, III = 12, IV = 6, and V = 9). Lesions with stent fracture had longer duration after implantation (172 days [interquartile range (IQR) 31 to 630 days] vs. 44 days [IQR 7 to 270 days], p = 0.004), a higher rate of Cypher (Cordis Corp., Miami Lakes, Florida) stent usage (63% vs. 36%, p = 0.001), longer stent length (30.0 mm [IQR 22.0 to 40.0 mm] vs. 20.0 mm [IQR 14.0 to 27.3 mm], p < 0.0001), and a higher rate of overlapping stents (45% vs. 22%, p = 0.003). Although fracture with grade I to IV did not have significant impact on the occurrence of adverse pathologic findings such as thrombosis and restenosis, 67% of the grade V fracture lesions were associated with adverse pathologic findings at fracture sites. Longer stent length, use of Cypher, and longer duration of implant were identified as independent risk factors of stent fracture by logistic regression analysis. CONCLUSIONS: The incidence of stent fracture was 29% lesions at autopsy, which is much higher than clinically reported. A high rate of adverse pathologic findings was observed in lesions with grade V stent fracture, whereas fracture with grade I to IV did not have a significant impact on the pathological outcome.

RATIONALE: Sirolimus-eluting coronary stents (SESs) and paclitaxel-eluting coronary stents (PESs) are used to reduce restenosis but have different sites of action. The molecular targets of sirolimus overlap with those of the peroxisome proliferator-activated receptor (PPAR)gamma agonist rosiglitazone (RSG) but the consequence of this interaction on endothelialization is unknown. OBJECTIVE: Using the New Zealand white rabbit iliac model of stenting, we examined the effects of RSG on SESs, PESs, and bare metal stents endothelialization. METHODS AND RESULTS: Animals receiving SESs, PESs, or bare metal stents and either RSG (3 mg/kg per day) or placebo were euthanized at 28 days, and arteries were evaluated by scanning electron microscopy. Fourteen-day organ culture and Western blotting of iliac arteries and tissue culture experiments were conducted. Endothelialization was significantly reduced by RSG in SESs but not in PESs or bare metal stents. Organ culture revealed reduced vascular endothelial growth factor in SESs receiving RSG compared to RSG animals receiving bare metal stent or PESs. Quantitative polymerase chain reaction in human aortic endothelial cells (HAECs) revealed that sirolimus (but not paclitaxel) inhibited RSG-induced vascular endothelial growth factor transcription. Western blotting demonstrated that inhibition of molecular signaling in SES+RSG-treated arteries was similar to findings in HAECs treated with RSG and small interfering RNA to PPARgamma, suggesting that sirolimus inhibits PPARgamma. Transfection of HAECs with mTOR (mammalian target of rapamycin) short hairpin RNA and with Akt2 small interfering RNA significantly inhibited RSG-mediated transcriptional upregulation of heme oxygenase-1, a PPARgamma target gene. Chromatin immunoprecipitation assay demonstrated sirolimus interferes with binding of PPARgamma to its response elements in heme oxygenase-1 promoter. CONCLUSIONS: mTOR/Akt2 is required for optimal PPARgamma activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing.

OBJECTIVE: We sought to clarify the mechanisms of backup force for right coronary artery intervention. BACKGROUND: Backup force of a guiding catheter is important for successful percutaneous coronary intervention (PCI); however, little attention has been given to its mechanism. METHODS AND RESULTS: Backup force of guiding catheters was measured in an arterial tree model. Judkins R, Amplatz L and Ikari R had greater backup force in the transfemoral intervention (TFI) than the transradial intervention (TRI). The primary attachment site of the catheter was the aortic arch in TFI, but it was the brachiocephalic artery in right TRI. This may be a major reason for the different backup force because generation of backup force is governed by the mechanics of the catheter at the attachment site. The Amplatz L and Ikari R had stronger backup force than the Judkins R both in TFI and in TRI because a slight backward motion of the catheter due to device advancement changed the primary attachment site to the reverse side of the aorta or sinus of Valsalva. The primary attachment site of the Ikari L at the power position was the reverse side of the aorta both in TFI and TRI, which was different from other catheters. CONCLUSIONS: The primary attachment site of the catheter had great impact on the backup force in right coronary interventions. An understanding of the mechanism by which the guiding catheter works in TRI and TFI may help in choosing an appropriate approach site.

BACKGROUND: Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. METHODS AND RESULTS: The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020+/-283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2+/-2.4 mm(2) and evidence of vessel remodeling (index, 1.6+/-0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263+/-149 white blood cells per high-power field) and eosinophils (DES, 20+/-24 eosinophils per high-power field; sirolimus-eluting stents, 34+/-28; paclitaxel-eluting stents, 6+/-6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20+/-24) than in those from spontaneous acute myocardial infarction (7+/-10), early bare-metal stent ST (1+/-1), early DES ST (1+/-2), and late bare-metal stent ST (2+/-3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area. CONCLUSIONS: Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

BACKGROUND: Percutaneous coronary intervention for hemodialysis patients has been hampered by the high rate of adverse cardiac events. Our aim was to investigate whether sirolimus-eluting stents (SESs) improve clinical outcomes of hemodialysis patients compared with bare-metal stents (BMSs). STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: 123 consecutive patients on hemodialysis therapy treated with either an SES or BMS. There were 56 patients with 68 lesions treated with SESs between August 2004 and April 2006 (SES group) and 67 patients with 71 lesions treated with BMSs 4 years before approval of SESs in Japan (BMS group). PREDICTOR: SES and BMS implantation for hemodialysis patients with coronary artery disease. OUTCOMES & MEASUREMENTS: Follow-up angiography was performed at 6 to 8 months and clinical follow-up was obtained at 9 months after the procedure. Late lumen loss and major adverse cardiac events, including all-cause death, myocardial infarction, and target-lesion revascularization, were investigated. RESULTS: Clinical follow-up was obtained in all patients. Angiographic follow-up was obtained in 50 patients (89.3%) in the SES group and 50 patients (74.6%) in the BMS group. The SES group had more complex lesions than the BMS group. Quantitative angiographic analysis showed a significant difference for in-stent late lumen loss (SES, 0.62 +/- 0.75 mm; BMS, 1.07 +/- 0.75 mm; P = 0.003). Of angiographic restenosis lesions analyzed, a focal restenotic pattern was observed more frequently in the SES group than the BMS group (SES, 87.5%; BMS, 23.8%; P < 0.001). The rate of major adverse cardiac events was significantly lower in the SES group (n = 14; 25.0%) than the BMS group (n = 26; 38.9%; log-rank P = 0.02). LIMITATIONS: Retrospective study design, small sample size, and a single-center study. CONCLUSIONS: Clinical and angiographic data in the present study suggest that SESs are more effective than BMSs in hemodialysis patients.

AIMS: This study was performed to assess the differences in culprit plaque composition between patients with and without pre-infarction angina (PA) by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency (RF) data. METHODS AND RESULTS: Of 57 patients consecutively admitted to our institution with acute myocardial infarction, pre-intervention IVUS RF data of culprit plaques were obtained and analysed in 35 patients after percutaneous aspiration thrombectomy. Among the 35 patients, 21 patients had PA. Culprit plaques of patients without PA consisted of a higher percentage of the necrotic core component than those with PA (minimum lumen area [MLA]) site, 21.2+/-8.9% versus 9.9+/-9.8%, p=0.0015; entire culprit lesion, 18.9+/-6.3% versus 12.0+/-9.6%, p=0.023). In contrast, culprit plaques of patients with PA contained a higher percentage of the fibrofatty component than those without PA (MLA site, 21.0+/-12.0% versus 11.5+/-7.6%, p=0.013; entire culprit lesion, 16.8+/-7.9% versus 12.1+/-5.5%, p=0.062). There was no significant difference in quantitative parameters between the patients with and without PA. CONCLUSIONS: Culprit plaques of patients with PA were different from those without PA. Plaque composition may play an important role in the occurrence of PA.

BACKGROUND: Although both sirolimus (CYPHER) and paclitaxel (TAXUS) drug-eluting stents have demonstrated efficacy and safety in clinical trials, human autopsy data have raised concerns about long-term healing and the potential for local inflammatory reactions. METHODS AND RESULTS: Overlapping stents (CYPHER drug-eluting stents, Bx SONIC bare metal stents, TAXUS drug-eluting stents, and Liberté bare metal stents) were implanted in noninjured coronary arteries of 58 domestic swine. Histopathological evaluation of proximal, overlapped, and distal stented segments was determined with emphasis on inflammation at 30, 90, and 180 days. Circumferential granulomatous inflammation in all stented segments was defined as inflammation consisting of macrophages, multinucleated giant cells, lymphocytes, and granulocytes, including many eosinophils, adjacent to almost all struts. Circumferential granulomatous inflammation was more prevalent in CYPHER (9 of 23, 39%) compared with TAXUS (1 of 21, 5%; P=0.01) and control bare metal stents (0 of 44) in the combined 90- and 180-day cohorts. Only CYPHER specimens showed marked adventitial inflammation (P=0.0025) and fibrosis (P=0.0055) accompanied by extensive remodeling. Fibrin deposition within neointima and medial smooth muscle cell death were greater (both P<0.001) in TAXUS than CYPHER at 30 days, with more fibrin in TAXUS than CYPHER through 90 days (P<0.05). CONCLUSIONS: Although these data cannot be directly extrapolated to humans, the high prevalence in this porcine model of diffuse granulomatous inflammation seen with CYPHER stents, persisting at 180 days and associated with extensive remodeling of the artery, and persistent para-strut fibrin deposition with TAXUS stents emphasize the need for further investigation of biocompatibility with these and other novel combination drug/polymer drug-eluting stents.

Drug-eluting stents (DES) have become the standard of care for the treatment of coronary artery disease. However, late stent thrombosis has emerged as a major concern, especially in 'off-label' use. Pathologic studies of patients dying from late DES thrombosis demonstrate delayed arterial healing, characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. Therefore, next-generation DES are being developed to increase the safety and biocompatibility by optimizing the three major components of DES: the stent platform, the polymer and the drug. Stents with thinner struts are endothelialized rapidly and cause less vessel-wall injury. Non-erodable polymers applied thinly and without defect or cracking cause less inflammation and will result in better long-term safety. Furthermore, use of biodegradable polymers, which fully degrade and leave a bare metal stent, will result in less inflammation. The choice of drug, dose and release kinetics should also be optimized. In addition to the improvement of DES components, new approaches, such as polymer-free drug delivery, prohealing approach and fully biodegradable stents, are emerging. Importantly, these technologies focus not only on efficacy but also on safety. The next-generation DES will probably be safer, with goals of improving endothelialization and more rapid arterial healing compared with first- and second-generation DES.

OBJECTIVE: TRM-484 is a novel drug consisting of nanoparticles of prednisolone with high affinity to chondroitin sulfate proteoglycans (CSPGs). This may allow for neointimal suppression via directed targeting to areas of injury at systemic concentrations low enough to avoid adverse side effects known to occur with oral delivery of steroids. METHODS AND RESULTS: Atherosclerotic New Zealand white Rabbits were implanted with bare metal stents and randomized to receive intravenous TRM-484 at doses of 1 mg/kg or 0.32 mg/kg starting at the day of stenting and continuing 3 times a week for the duration of the study. Control animals received empty liposomes (placebo) or saline infusion. Stented arterial segments were harvested at 42 days and processed for histomorphometry and immunohistochemistry. Tissue and plasma levels were determined along with confocal microscopic analysis to determine distribution of rhodamine-labeled TRM-484 at various time points. TRM-484 was exclusively observed at sites of stent-induced injury, with absence of drug in contralateral nonstented arteries. Tissue concentration of stented arteries exceeded that of contralateral nonstented arteries by 100-fold 24 hours after administration of 1 mg/kg TRM-484 and resulted in significant reduction of percent stenosis compared to saline and placebo treated rabbits (22.5+/-4.4 versus 31.0+/-8.4 and 29.5+/-8.1%, P<0.03). CONCLUSIONS: TRM-484 at doses of 1 mg/kg resulted in significant suppression of in-stent neointimal growth in atherosclerotic rabbits. Site-specific targeting by this nanoparticle steroid in injured atherosclerotic areas might be a valuable and cost-effective approach for the prevention of in-stent restenosis.

After pivotal clinical trials, drug-eluting stents (DES) are now considered the standard of care for the management of acute coronary syndrome. However, late stent thrombosis has emerged as a major concern. Preclinical testing is an important regulatory process that determines the safety and efficacy of devices prior to human clinical trials. Histopathologic analysis following placement of DES has typically been performed in porcine coronary artery models to ensure safety in these devices. The recently issued consensus report from the US FDA, for the approval of DES recommends the use of the porcine model for the safety assessment of these devices in the vascular bed for which they are intended. Other models are also recommended, as vascular responses to stents are much slower in man than in animals, and no animal truly elicits the response seen in humans. The rabbit iliac artery can provide further data, especially regarding endothelialization, which is slower in the rabbit model than in the porcine model. Furthermore, inflammation is not as extensive in the rabbit and may thus be a closer model of humans than the porcine models. The FDA recognizes that it may be more appropriate to test these devices in atherosclerosis. The choice of animal model may mask the serious drawbacks of the devices; therefore, we suggest the use of both models to understand the healing following DES implantation, with emphasis on endothelialization, inflammation and neointimal formation and, whenever possible, to complement the observations in the environment of atherosclerosis.

BACKGROUND: The long-term safety of drug-eluting stents (DES) for acute myocardial infarction (AMI) remains uncertain. Using autopsy data, we evaluated the pathological responses of the stented segment in patients treated with DES for AMI and compared with patients with stable angina. METHODS AND RESULTS: From the CVPath Registry of 138 DES autopsies, we identified 25 patients who presented with AMI and had an underlying necrotic core with a ruptured fibrous cap. Twenty-six patients who had stable angina with thick-cap fibroatheroma treated by DES were selected as controls. Histomorphometric analysis was performed in patients with >30-day stent duration. We compared the response to stenting at the culprit site in these 2 groups and to nonculprit sites within each stent. Late stent thrombosis was significantly less frequent in stable (11%) than in AMI (41%; P=0.04) patients. Although neointimal thickness in the AMI culprit site was significantly less (median, 0.04 mm; interquartile range [IQR], 0.02 to 0.09 mm), the prevalence of uncovered struts (49%; IQR, 16% to 96%), fibrin deposition (63+/-28%), and inflammation (35%; IQR, 27% to 49%) were significantly greater compared with the culprit site in stable patients (neointimal thickness: 0.11 mm [IQR, 0.07 to 0.21 mm], P=0.008; uncovered struts: 9% [IQR, 0% to 39%], P=0.01; fibrin: 36+/-27%, P=0.008; inflammation, 17% [IQR, 7% to 25%], P=0.003) and the nonculprit site within each stent. CONCLUSIONS: Vessel healing at the culprit site in AMI patients treated with DES is substantially delayed compared with the culprit site in patients receiving DES for stable angina, emphasizing the importance of underlying plaque morphology in the arterial response to DES. Our data suggest an increased risk of thrombotic complications in patients treated with DES for AMI.

BACKGROUND: The difference in the culprit plaque composition of acute coronary syndrome (ACS) patients with and without the no-reflow phenomenon has not been fully evaluated. METHODS AND RESULTS: Intravascular ultrasound radiofrequency data of culprit plaques were obtained and analyzed in 49 ACS patients. The no-reflow phenomenon was defined as a decrease of at least 1 grade in 'Thrombolysis In Myocardial Infarction' flow immediately after mechanical dilatation compared with before mechanical dilatation, with no evidence of thrombus, spasm, or dissection. The no-reflow phenomenon was observed in 9 individuals. Culprit plaques with the no-reflow phenomenon contained a higher percentage of necrotic core component and a smaller percentage of fibrous component than plaques in the patients without the no-reflow phenomenon (necrotic core component, 22.1+/-9.3% vs 11.7+/-7.9%, p=0.0011; fibrous component, 59.6+/-11.2% vs 68.3+/-10.2%, p=0.027). Multivariate analysis identified the percentage of necrotic core component as an independent predictor of the no-reflow phenomenon after adjustment for plaque geometry and procedural factors (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.5; p=0.015). CONCLUSION: Culprit plaques of patients with the no-reflow phenomenon differ from those in patients without the no-reflow phenomenon.

Drug eluting stents (DES) have expanded the use of stents for the treatment of coronary atherosclerotic disease with significant reduction in restenosis rates. However, DES have been associated with late stent thrombosis (LST), especially when used for "off-label" indications. Although similar cellular processes control the early response after both bare metal (BMS) and DES placement, the more chronic response and time course of healing is markedly different between BMS and DES. There is persistence of fibrin beyond the 12-month period and re-endothelialisation is incomplete with some struts remaining uncovered beyond the 2-year period, a strong predictor for LST. While vessel wall injury correlated with restenosis in the BMS era, its impact has been minimised by the use of DES, which is likely related to the use of powerful antiproliferatives with prolonged release kinetics which profoundly inhibit the reparative response to arterial injury. However, at the same time, vessel injury secondary to drug toxicity or inflammation caused by polymer is observed following DES implantation. Nonerodable polymers induce granulomatous and hypersensitivity reactions in animal models and this has been observed exclusively with the use of Cypher stents in man. On the other hand the Taxus stent is associated with medial necrosis, positive remodelling and excessive fibrin deposition, all likely cytotoxic effects of paclitaxel. Both may lead to late stent thrombosis. Other factors that increase risk are penetration of the necrotic core, bifurcation stenting and malapposition.

OBJECTIVES: The purpose of this study was to assess trends in endothelial coverage and recovery among leading polymer-based drug-eluting stents (DES). BACKGROUND: Autopsy studies of human U.S. Food and Drug Administration (FDA)-approved DES implanted coronary arteries suggest that complications of late stent thrombosis are associated with incomplete endothelial coverage of struts. METHODS: Rabbits received sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES), zotarolimus-eluting stents (ZES), and everolimus-eluting stents (EES) for 14 or 28 days along with MULTI-LINK (ML) Vision control stents. Endothelial coverage above and between struts was measured by morphometric analysis of images acquired through en face scanning electron microscopy. Dual fluorescent immunolabeling was performed for platelet-endothelial cell adhesion molecule (PECAM)-1 and thrombomodulin (TM), factors involved in cell-to-cell contact and thrombogenicity, respectively. In a separate analysis, the endothelial mitogen, vascular endothelial growth factor (VEGF), was also assessed. RESULTS: Varying rates of endothelialization among comparator DES were most notable at 14 days, where coverage above struts remained poor in SES, PES, and ZES (or=70%), whereas no significant differences were observed at 28 days. Select DES with poor endothelialization showed a further reduced expression of PECAM-1. All DES showed an absence or weak expression of the antithrombotic cofactor TM. Incomplete endothelialization in select DES was further associated with increased VEGF secretion and messenger ribonucleic acid levels at 14 days, providing evidence of a transitional healing surface. CONCLUSIONS: The present study marks the first comparator analysis of endothelial coverage in leading polymeric DES, supporting disparities in arterial healing based on endothelial regrowth and recovery, favoring newer designs over the current generation of FDA-approved stents.

Compared to bare-metal stents (BMS), drug-eluting stents (DES) provide a significant additional reduction in restenosis rates and the need for coronary reinterventions. However, compared to BMS, the risk of very late stent thrombosis (ST) appears to be marginally higher accounting for 0.2-0.6% annual incidence for up to 3 years and possibly even longer following implantation. Risk reduction strategies include meticulous implantation technique, identification of patients with increased thrombotic risk, exclusion of patients scheduled in short term for major elective surgeries, and extended dual antithrombotic treatment for a minimum of 12 months. Future risk avoidance strategies are briefly reviewed and commented.

BACKGROUND: Metallic allergy is associated with restenosis following bare metal stent implantation, but the impact of metallic allergy on the outcome after implantation of drug-eluting stents (DES) has not been investigated. METHODS AND RESULTS: The present study group consisted of 88 consecutive patients (109 lesions) who underwent percutaneous coronary intervention with sirolimus-eluting stents (SES). Follow-up angiography was obtained at 8 months in all patients. At that time, the patients underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and titanium, which were evaluated after 48 h of contact. The patch test was positive in 14 patients (16%) (5 for manganese, 3 for nickel, 1 for chromate, 1 for Nickel and manganese, and 4 for manganese and chromate). The binary restenosis rate in the patients with a positive patch test was similar to those with negative patch test (6.3% vs 6.5%, p=0.98). Serial quantitative coronary angiography analyses identified no significant differences in late lumen loss of in-stent segments between patients with positive patch test and those with negative patch test (0.19+/-0.49 mm vs 0.12+/-0.48 mm, p=0.55). CONCLUSION: SES prevent restenosis irrespective of metallic allergy. The classic relationship between metallic allergy and in-stent restenosis, seen with bare metal stents, does not appear to arise with DES, possibly because of the immunosuppressive effect of sirolimus.

BACKGROUND: It has been reported that multidetector spiral computed tomography (MDCT) allows the classification of coronary plaques by measuring computed tomography (CT) density values. However, the impact of CT density values in culprit lesions on the occurrence of transient no-reflow during percutaneous coronary intervention (PCI) has not been investigated. METHODS: The study population consisted of 51 consecutive patients who were diagnosed as having coronary artery disease by 64-slice MDCT before PCI. The CT density values were measured in multiple cross-sectional images along the plaque by 5-pixel regions of interest at multiple sites in the culprit plaque. The measurements were performed by 2 physicians who were unaware of the outcome of PCI. In addition, we describe a new observation noted on MDCT: from the formal resemblance to a ring, we dubbed these images as showing a "signet ring-like appearance." RESULTS: Of the total 51 patients, 9 had transient no-reflow during the procedure. There was a significant difference in CT density of the culprit plaque between patients with transient no-reflow and those without (67.0 +/- 10.1 vs 97.8 +/- 37.2 Hounsfield units, P = .018). In addition, a signet ring-like appearance was observed more frequently in patients with transient no-reflow (55.6% vs 16.7%, P = .013). By multivariate analysis, low CT density value and ejection fraction were identified as independent predictors of transient no-reflow. CONCLUSIONS: The assessment of plaque characteristics by MDCT might be useful for the prediction of transient no-reflow during PCI.

Comparative preclinical histologic studies remain the most effective method for assessing the healing characteristics of vascular stents. The 2 most commonly used animal models to assess vascular responses to stent implantation are the porcine coronary artery and the rabbit iliac artery. Neither model alone is comparable to the human response to the implantation of a drug-eluting stent (DES). In the rabbit model at 28 days, the pathologies of the zotarolimus-eluting stent (ZES), the paclitaxel-eluting stent (PES), the sirolimus-eluting stent (SES), and a bare metal stent (BMS) were assessed. There was less inflammation with the ZES than with the SES or PES, and there were uncovered struts with the SES and PES but not with the ZES and BMS. In the pig model at 30, 90, and 180 days, the pathologies of the ZES, SES, and BMS were assessed. At 30 days, the thickness of neointima and the grade of inflammation were less with the SES than with the ZES and BMS, but at 90 and 180 days, the measures increased for the SES and were greater than those with the ZES and BMS, whereas the measures for the ZES and BMS did not change over time. In the rabbit model, the endothelialization of overlapping the SES, PES, and ZES was assessed. There was significantly greater endothelialization in the area above stent struts in the overlapping segment for the ZES than for the SES (p = 0.028). The level of endothelialization for the PES was less than that for the ZES, but the difference was not significant. Because arterial healing is multifactorial, it is extremely important that the next generation of DESs undergo preclinical testing in pig and rabbit models to examine endothelialization, inflammation, release kinetics, and neointimal reduction to establish the safety of these devices in humans.

PURPOSE OF REVIEW: Free cholesterol in plaques is an emerging contributing factor to lesion instability and, until recently, apoptosis of lipid-laden macrophages was considered the major source of free cholesterol. The validity of this concept is beginning to be challenged since there is recent evidence of erythrocyte membrane-derived cholesterol in plaques. Therefore, intraplaque hemorrhage may not be a passive event, as once considered as studies continue to support the relationship of intraplaque hemorrhage and necrotic core expansion. RECENT FINDINGS: The association of intraplaque hemorrhage, accumulated free cholesterol, and necrotic core expansion is beginning to unfold and recent MRI studies suggest the value of intraplaque hemorrhage as a predictor of recurrent cerebrovascular events. The amount of erythrocyte membrane-derived cholesterol is also suggested to be a measure of lesion vulnerability in acute coronary syndromes. Recent inhibitors studies of vascular permeability factors further emphasize the importance of intraplaque hemorrhage in plaque progression. Finally, DNA microarray analysis is starting to reveal key molecules involved in the accumulation of free cholesterol that are selectively induced in high-risk plaques. SUMMARY: These recent findings emphasize the importance of intraplaque hemorrhage as a contributor of free cholesterol in plaques and point to its provocative role in lesion destabilization.

Atherosclerotic plaque at the carotid bifurcation is the primary cause of ischemic strokes and the degree of carotid stenosis is strongly associated with stroke risk in symptomatic patients. Stroke is the third-leading cause of death in the United States, constituting approximately 700,000 cases each year. In this article, the authors discuss the natural history of carotid and intracranial atherosclerosis, based on their broader knowledge of coronary atherosclerosis. Early to more advanced progressive lesions of the carotid are categorized, based on descriptive morphologic events originally cited for the coronary circulation. The histologic features associated with symptomatic and asymptomatic carotid disease are also addressed, along with the issues surrounding current stent-based therapies for the prevention of major recurrent vascular events.

OBJECTIVES: The aim of this study was to compare the effects of systemic prednisone in combination with a bare-metal stent (BMS) or a paclitaxel-eluting stent (Taxus, Boston Scientific Corp., Natick, Massachusetts) on neointimal inhibition and vessel healing in an atherosclerotic rabbit model. BACKGROUND: Inflammation plays a critical role in neointimal formation after coronary artery stenting. The efficacy of immunosuppressive doses of oral prednisone to inhibit in-stent neointimal proliferation was compared with BMS and with a commercially available paclitaxel-eluting stent (Taxus) in a rabbit model of established atherosclerosis. METHODS: Bilateral iliac artery injury in atherosclerotic New Zealand White rabbits fed an atherogenic diet was followed by stent implantation. Animals randomly received Taxus stents, BMS (Express, Boston Scientific Corp.) and placebo, or BMS and oral prednisone (2.1 mg/kg/day for the first 7 days, followed by 1.4 mg/kg/day for 14 days and 0.7 mg/kg/day for 21 days). Stented arterial segments were harvested at 42 days and processed for light microscopy, immunohistochemistry, and organoid culture. RESULTS: Compared with control subjects, prednisone-treated animals showed a 30% reduction in percent stenosis (p = 0.009), a 35% decrease in neointimal area (p < 0.003), and a 66% decrement in neointimal thickness (p < 0.001). Taxus stents also reduced all 3 parameters significantly (-34%, -39%, and -83%, respectively), but showed significantly more inflammatory cells and fibrin deposition and less endothelialization compared with the other 2 groups. Plaque burden was equal among groups, as shown by the identical stent and vessel area, and no remodeling was observed. CONCLUSIONS: Systemic prednisone treatment and Taxus stents reduce neointimal formation compared with BMS. The extent of neointimal reduction is similar between prednisone- and Taxus stent-treated animals; however, Taxus stents resulted in a significantly greater delay in healing. Targeting of inflammatory pathways after percutaneous coronary intervention may be an efficacious way to prevent restenosis without the long-term risk of late thrombosis.

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting stents have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI). Although these stents reduce rates of restenosis compared with bare metal stents (BMS), late thrombosis, a life threatening complication, has emerged as a major safety concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared with BMS. This delayed healing is the primary substrate underlying all cases of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis such as penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions represent additional barriers to healing and should be avoided if DES are to be used to minimize the risk of late thrombosis. Because the time course of complete healing with DES in man is unknown, the optimal duration of antiplatelet treatment remains to be determined.

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting stents (Taxus), so-called drug-eluting stents (DES), have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary revascularization (PCI). While these stents have reduced rates of restenosis and late lumen loss compared to bare-metal stents (BMS), late thrombosis, a life-threatening complication of this technology, has emerged as a major concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that the DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared to BMS. This so-called delayed healing is "identified as" the primary substrate of an underlying cause of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis include penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions. These represent additional barriers to healing and should be avoided if DES are to be used in order to minimize the late thrombotic risks of these devices. Since the time course of complete healing with DES is unknown, the optimal duration of antiplatelet treatment remains to be determined.

BACKGROUND: Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent placement has emerged as a major concern. Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown. METHODS AND RESULTS: From a registry totaling 81 human autopsies of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted >30 days. We identified 28 lesions with thrombus and compared those with 34 of similar duration without thrombosis using computer-guided morphometric and histological analyses. LST was defined as an acute thrombus within a coronary artery stent in place >30 days. Multiple logistic generalized estimating equations modeling demonstrated that endothelialization was the best predictor of thrombosis. The morphometric parameter that best correlated with endothelialization was the ratio of uncovered to total stent struts per section. A univariable logistic generalized estimating equations model of occurrence of thrombus in a stent section versus ratio of uncovered to total stent struts per section demonstrated a marked increase in risk for LST as the number of uncovered struts increased. The odds ratio for thrombus in a stent with a ratio of uncovered to total stent struts per section >30% is 9.0 (95% CI, 3.5 to 22). CONCLUSIONS: The most powerful histological predictor of stent thrombosis was endothelial coverage. The best morphometric predictor of LST was the ratio of uncovered to total stent struts. Heterogeneity of healing is a common finding in drug-eluting stents with evidence of LST and demonstrates the importance of incomplete healing of the stented segment in the pathophysiology of LST.

BACKGROUND: Sirolimus-eluting stents (SES) have been demonstrated to reduce restenosis. However, there have been few studies evaluating the impact of renal insufficiency on the angiographic as well as clinical outcomes after SES implantation. METHODS: This study was composed of 304 consecutive patients having 361 lesions who underwent percutaneous coronary intervention with SES. The patients were divided into 3 groups according to renal function (group 1 [n = 204]; creatinine clearance (Ccr) > or = 60 ml/min, group 2 [n = 69]; Ccr < 60 ml/min, group 3 [n = 31]; hemodialysis). Clinical and angiographic follow-up were evaluated at 8 months. RESULTS: Clinical follow-up was obtained in all patients and angiographic follow-up was obtained in 283 patients (93.1%). Patients in group 3 showed a higher incidence of previous coronary artery bypass graft surgery, and there were more female gender, hypertensive, and less hyperlipidemia in this group. Late lumen loss at 8 months was significantly different among the 3 groups (group 1; 0.16 +/- 0.46 mm, group 2; 0.44 +/- 0.62 mm, group 3; 0.81 +/- 0.88 mm, P < 0.0001). Major adverse cardiac events (MACE) were documented in 22 patients (10.8%) in group 1, 13 patients (18.8%) in group 2, and 12 patients (38.7%) in group 3, respectively (P = 0.0002). CONCLUSION: Neointimal growth following SES implantation is more pronounced in patients with renal insufficiency, especially those undergoing dialysis, compared with patients with normal renal function. Regardless of the beneficial effect of SES, the increased risk of MACE mainly due to high incidence of target vessel revascularization in the subgroup of patients with renal insufficiency should be taken into account.

BACKGROUND: The relationship between coronary artery remodeling and culprit plaque composition in vivo has not been fully evaluated by spectral analysis of intravascular ultrasound (IVUS) radiofrequency (RF) data. METHODS AND RESULTS: IVUS RF analyses were performed for 56 consecutive de novo culprit lesions of 52 patients undergoing percutaneous coronary intervention. Remodeling of culprit lesions was determined using the remodeling index (RI), calculated as the external elastic membrane area of the minimum lumen area (MLA) site divided by that of the proximal reference site. Positive remodeling was defined as RI >1.05, intermediate remodeling as 0.95< or = RI < or =1.05 and negative remodeling as RI <0.95. Among the 56 lesions, positive remodeling was detected in 24, intermediate remodeling in 16, and negative remodeling in 16. At MLA sites, positive remodeling lesions had a larger percentage of the fibrofatty component than negative remodeling lesions (22.5+/-10.3% vs 10.4+/-6.6%, p=0.0001), whereas the latter contained a larger percentage of the dense calcium component than the former (2.8+/-2.9% vs 8.4+/-7.0%, p=0.016). CONCLUSIONS: Culprit plaques with positive remodeling have a large lipid burden, whereas those with negative remodeling contain a large amount of calcium.

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.

BACKGROUND: Stent fracture is one of the possible causes of restenosis after sirolimus-eluting stents (SES) implantation. The aim of our study was to evaluate the prevalence and clinical impact of coronary stent fracture after SES implantation. METHODS: From our prospective institutional database, 280 patients were treated solely with SES from August 2004 to June 2005. Among the 280 patients, 256 patients with a total of 307 lesions underwent follow-up angiography on an average of 240 days after the procedure. RESULTS: Stent fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent fracture, five were located in the right coronary artery (RCA), two in the saphenous vein (SV) graft, and one in the left anterior descending coronary artery. The stent fractures were all in the locations that served as hinges during vessel movement in the cardiac contraction cycle. Seven of the eight stent fractures were adjacent to the edge of previously implanted or overlapped stent. Significant multivariate predictors of stent fracture were SV graft location (Odds ratio 35.88; 95% confidence interval 2.73-471.6, P = 0.006), implanted stent length (Odds ratio 1.04; 95% confidence interval 1.01-1.07, P = 0.02), and RCA location (Odds ratio 10.00; 95% confidence interval 1.11-89.67, P = 0.04). In-stent binary restenosis rate was 37.5% and target lesion repeat revascularization rate was 50.0% in patients with stent fracture. CONCLUSIONS: Stent fracture was likely to be affected by mechanical stress provoked by rigid structures and hinge points. Stent fracture might be associated with the high incidence of target lesion revascularization.

OBJECTIVE: To characterize various dysgraphic symptoms in parietal agraphia. METHOD: We examined the writing impairments of four dysgraphia patients from parietal lobe lesions using a special writing test with 100 character kanji (Japanese morphograms) and their kana (Japanese phonetic writing) transcriptions, and related the test performance to a lesion site. RESULTS: Patients 1 and 2 had postcentral gyrus lesions and showed character distortion and tactile agnosia, with patient 1 also having limb apraxia. Patients 3 and 4 had superior parietal lobule lesions and features characteristic of apraxic agraphia (grapheme deformity and a writing stroke sequence disorder) and character imagery deficits (impaired character recall). Agraphia with impaired character recall and abnormal grapheme formation were more pronounced in patient 4, in whom the lesion extended to the inferior parietal, superior occipital and precuneus gyri. CONCLUSION: The present findings and a review of the literature suggest that: (i) a postcentral gyrus lesion can yield graphemic distortion (somesthetic dysgraphia), (ii) abnormal grapheme formation and impaired character recall are associated with lesions surrounding the intraparietal sulcus, the symptom being more severe with the involvement of the inferior parietal, superior occipital and precuneus gyri, (iii) disordered writing stroke sequences are caused by a damaged anterior intraparietal area.

BACKGROUND: Studies in Western countries have shown that sirolimus-eluting stents (SES) are clinically effective in the real world, but the detailed serial angiographic analyses are limited to some complex lesions. In addition, the efficacy of SES has not been fully investigated in a Japanese population. METHODS AND RESULTS: The study population consisted of 249 consecutive unselected patients who underwent percutaneous coronary intervention (PCI) with SES. Clinical and angiographic follow-up were evaluated at 8 months. Clinical follow-up was obtained in all patients and angiographic follow-up was obtained in 228 patients (91.6%) with 272 lesions (91.0%). Major adverse cardiac events were documented in 44 patients (17.7%). There were 2 stent thromboses within 24 h and 11 days after PCI (0.8%). Late lumen loss in the proximal edge, in-stent, and distal edge was 0.06+/-0.44 mm, 0.26+/-0.60 mm, and -0.05+/-0.30 mm, respectively. The rate of angiographic in-segment binary restenosis was 14.0% (proximal edge: 3.3%, in-stent: 10.7%, distal edge: 0.7%). By multivariate analysis, an increased risk of restenosis was significantly associated with hemodialysis, diabetes, lesion length, and impaired left ventricular ejection fraction. CONCLUSION: In accordance with previous reports, SES is considered to be feasible, safe and effective based on the results in an unselected Japanese population. ).

BACKGROUND: A prospective, randomised, single centre study was designed to test the safety and efficacy of nicorandil infusion, a potassium channel opener, prior to reperfusion in ST-elevation acute myocardial infarction (STEMI). METHODS AND RESULTS: Seventy STEMI patients with TIMI 0 to 2 flow were randomly assigned to nicorandil (Group N; n = 35) or control (Group C; n = 35) and underwent direct percutaneous coronary intervention (PCI). In Group N, 2 mg of nicorandil was infused directly into the infarct area prior to reperfusion. Incidence of anterior infarction was 60% in both groups. With nicorandil infusion, additional ST elevations without chest pain were observed for a few minutes in 94% of cases. However, no ventricular fibrillation or ventricular tachycardia occurred. TIMI myocardial perfusion grade 3 was significantly higher in Group N (40% vs. 17%, p<0.01). Patients were followed for up to 8 months, with similar incidence of major clinical adverse events, however left ventricular regional wall motion score significantly improved in Group N (P < 0.05). The effect of nicorandil was seen in patients without ischaemic preconditioning (P < 0.05). CONCLUSION: This study suggests that direct infusion of nicorandil prior to revascularisation may be safe and beneficial.

OBJECTIVES: We investigated the frequency of the noncardiac findings in cardiac imaging with multidetector computed tomography (MDCT). BACKGROUND: Multidetector computed tomography is an accepted new tool to evaluate the heart. In cardiac MDCT scans, organs other than the heart are also irradiated, but usually not assessed. METHODS: A total of 503 patients underwent cardiac imaging with 16- or 64-slice MDCT. Cardiologists assessed the heart, while radiologists reviewed the other organs. RESULTS: A total of 346 new, noncardiac findings were identified in 292 patients (58.1%). A total of 114 patients (22.7%) had clinically significant findings including 4 cases of malignancy (0.8%). CONCLUSIONS: There were a significant number of noncardiac findings in cardiac MDCT. To avoid missing clinically important findings, physicians who analyze cardiac MDCT scan--either radiologists or cardiologists--should carefully evaluate all the organs irradiated in the scan.

BACKGROUND: Relation between metallic allergy and in-stent restenosis (ISR) has been inconclusive. We hypothesized that mechanism of restenosis is different between initial stent implantation and dilatation for ISR. Thus, we studied metallic allergy and restenosis in these two different situations separately. METHODS AND RESULTS: We performed follow-up angiography and patch test for metallic allergy in a total of 174 stented consecutive patients, 109 patients (63%) for restudy of initial stent implantation and 65 patients (37%) for restudy of treatment following ISR. The positive rate of patch test in initial stent implantation was not significantly different between with or without restenosis (10% vs. 9%; p=ns). Whereas, following dilatation of ISR, the incidence of positive patch test was significantly higher in patients with recurrence of restenosis than those without the recurrence (39% vs. 12%; p=0.02). Multivariate analysis revealed that the positive patch test (Odd Ratio 4.39, p=0.02) and diffuse typed ISR (Odd Ratio 3.68, p=0.03) were significant predictors of recurrent restenosis. CONCLUSIONS: Metal allergy does not have any correlation with the restenosis after initial stent implantation. However, metal allergy is frequently observed in patients with recurrence of ISR. Metal allergy may contribute to a mechanism in the repeat recurrence of ISR, but not to restenosis after initial stent implantation.

BACKGROUND AND PURPOSE: Prevalence of carotid artery stenosis in patients with coronary artery disease (CAD) is unknown in Japanese population. METHODS: The study populations consisted of 632 consecutive patients who underwent coronary angiography because of suspicion of CAD. All patients underwent carotid ultrasonography to screen carotid artery stenosis before coronary angiography. We defined echographic carotid stenosis as area stenosis of >50% or peak systolic velocity of >200 cm/s. RESULTS: Echographic carotid stenosis was observed in 124 patients (19.6%). Coronary angiography revealed 433 patients had CAD. Prevalence of echographic carotid artery stenosis was 14 of 199 (7.0%), 18 of 124 (14.5%), 28 of 131 (21.4%), and 64 of 178 (36.0%) in patients with 0-, 1-, 2-, and 3-vessel CAD, respectively (P<0.0001). The prevalence rate with carotid stenosis and CAD was 25.4%. Multivariate stepwise logistic regression analysis showed that age and the extent of CAD were independently related to the presence of carotid stenosis (P=0.0002 and <0.0001, respectively). CONCLUSIONS: Prevalence of carotid stenosis in patients with CAD is high in Japan as well as in Western countries. Screening of carotid artery stenosis is recommended especially in older patients with multivessel CAD.

Ikari is a new guide catheter for transradial intervention (TRI) that produces stronger back-up force by utilizing an unfavorable angle between the subclavian and brachiocephalic arteries. We report the initial results of the Ikari guide catheter based on the experience of a single center. Six operators performed a total of 102 coronary interventions for 91 patients using the Ikari guide catheter, while 101 interventions were performed with the transfemoral approach (TFI) during the same period. A left Ikari catheter was used in 63 procedures, and a right Ikari catheter was used in 39. The success rate for the procedure was 97% with a 6 French Ikari catheter. All failures were due to tortuous brachiocephalic arteries. For the Ikari procedure, the average fluorescence time was 14.5 9.5 minutes and the dye volume used was 153 53 ml; these results were equal to or better than those of TFI during the same period (20.1 12.2 minutes and 184 61 ml, respectively). These preliminary data suggest that an acceptable success rate can be achieved in TRI using appropriate guides, such as an Ikari catheter.

剖検例の収集は順調に進んでおり、現在順次病理解析を行っている。 第三世代薬剤溶出ステントにおける再内皮化のスピードにつき解析を行っており、第二世代薬剤溶出ステントよりも良好なHealing profileを呈している可能性がある。さらに解析を進めて学会発表等の準備を進めていく。

Treatment of coronary chronic total occlusion (CTO) is the biggest challenge of percutaneous coronary intervention (PCI). However, both clinical data and development of devices that alter treatment success rates are very limited. Accordingly, we performed 1) analyses of clinical data of CTO-PCI, 2) investigation of anatomy of CTO vessels for improvement of success rates, and 3) development of a prototype of dedicated device. 1) Using treatment of 525 CTO lesions, long-term clinical outcomes and substantial effects of initial lesion difficulty on the long-term patency rates were clarified. 2) Distribution of coronary calcification that strongly affects treatment success rates is under investigation by optical coherence tomography. 3) Development of 20 MHz alley ultrasound transducer which can be mounted on the tip of catheter was completed.