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: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). CONCLUSIONS: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low-, moderate-, and high-load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low-load (25 W) exercise was significantly lower in men, although that at maximum-load exercise was not different between men and women. In the Kaplan–Meier analysis, in a median follow-up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low-load exercise showed poorer survival (P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low-load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low-load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.

Two randomized control trials demonstrated that transcatheter aortic valve implantation was associated with 1-2 year clinical outcomes comparable or even superior to surgical aortic valve replacement (SAVR) in low surgical risk patients with severe aortic stenosis (AS). However, no previous study has reported the clinical outcomes after SAVR in Japanese patients with low surgical risk. From 3815 consecutive patients enrolled in the CURRENT AS registry, we retrieved 220 patients who underwent SAVR in reference to the inclusion and exclusion criteria of the PARTNER 3 trial. Age and surgical risk score in the current study population were comparable to those in the PARTNER 3 trial (Age: 75 years versus 74 years, and STS-PROM score: 2.3 versus 1.9). The cumulative incidence of a composite all-cause death or stroke was comparable between the current study population and the SAVR patients in the PARTNER 3 trial both at 30-day (2.3% versus 3.3%), and at 1-year (4.1% versus 4.9%). The clinical outcomes of SAVR in low surgical risk patients with severe AS selected from a real world Japanese registry according to the inclusion and exclusion criteria of the PARTNER 3 trial was favorable and numerically comparable to those of SAVR patients in the PARTNER 3 trial.

In the original publication of the article, the text citations of the Figs. 4-1, 4-2 and 5 should be Figs. 4, 5 and 6.

BACKGROUND: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan. METHODS AND RESULTS: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69). CONCLUSIONS: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.

AIMS: Early aortic valve replacement (AVR) might be beneficial in selected high-risk asymptomatic patients with severe aortic stenosis (AS), considering their poor prognosis when managed conservatively. This study aimed to develop and validate a clinical scoring system to predict AS-related events within 1 year after diagnosis in asymptomatic severe AS patients. METHODS AND RESULTS: We analysed 1274 asymptomatic severe AS patients derived from a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan (CURRENT AS registry), who were managed conservatively and completed 1-year follow-up without AVR. From a randomly assigned derivation set (N = 849), we developed CURRENT AS risk score for the AS-related event (a composite of AS-related death and heart failure hospitalization) within 1 year using a multivariable logistic regression model. The risk score comprised independent risk predictors including left ventricular ejection fraction <60%, haemoglobin ≤11.0 g/dL, chronic lung disease (2 points), diabetes mellitus, haemodialysis, and any concomitant valve disease (1 point). The predictive accuracy of the model was good with the area under the curve of 0.79 and 0.77 in the derivation and validation sets (N = 425). In the validation set, the 1-year incidence of AS-related events was much higher in patients with score ≥2 than in patients with score ≤1 (Score 0: 2.2%, Score 1: 1.9%, Score 2: 13.4%, Score 3: 14.3%, and Score ≥4: 22.7%, P < 0.001). CONCLUSION: The CURRENT-AS risk score integrating clinical and echocardiographic factors well-predicted the risk of AS-related events at 1 year in asymptomatic patients with severe AS and was validated internally.

BACKGROUND: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016). CONCLUSIONS: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.

OBJECTIVES: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. BACKGROUND: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. METHODS: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. RESULTS: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77). CONCLUSIONS: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

BACKGROUND: There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians' recommendations.Methods and Results:Among 3,815 consecutive patients with severe aortic stenosis (AS) enrolled in the CURRENT AS registry, the study population comprised 2,005 symptomatic patients, who were subdivided into 3 groups by their treatment strategy and the reasons for conservative strategy (Initial AVR group: n=905; Patient rejection group: n=256; Physician judgment group, n=844). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalization. Patients in the patient rejection group as compared with those in the physician judgment group were younger, and had less comorbidities, and lower surgical risk scores. The cumulative 5-year incidence of the primary outcome measure in the patient rejection group was markedly higher than that in the initial AVR group, and was similar to that in the physician judgment group (60.7%, 19.0%, and 66.4%, respectively). CONCLUSIONS: Patient rejection was the reason for non-referral to AVR in nearly one-quarter of the symptomatic patients with severe AS who were managed conservatively. The dismal outcome in patients who refused AVR was similar to that in patients who were not referred to AVR based on physician judgment despite less comorbidities and lower surgical risk scores in the former than in the latter.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5-year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56-3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01-1.78, P=0.04, respectively). Conclusions AVA ≤0.6 cm2 would be a useful marker to identify those high-risk patients with asymptomatic severe AS, who might benefit from early AVR. Clinical Trial Registration URL: www.umin.ac.jp . Unique identifier: UMIN000012140.

Prognostic impact of anemia complicating severe aortic stenosis (AS) remains unclear. We assessed the impact of anemia on cardiovascular and bleeding outcomes in 3403 patients enrolled in the CURRENT AS registry. 835 patients (25%) had mild (hemoglobin 11.0-12.9 g/dl for men/11.0-11.9 g/dl for women) and 1282 patients (38%) had moderate/severe anemia (Hb <= 10.9 g/dl) at diagnosis of severe AS. Mild and moderate/severe anemia were associated with significantly increased risks relative to no anemia (hemoglobin >= 13.0 g/dl for men/>= 12.0 g/dl for women) for the primary outcome measure (aortic valverelated death or heart failure hospitalization) in the entire population [hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.07-1.57 and HR: 1.56; 95% CI: 1.31-1.87, respectively] and in the conservative management stratum (HR: 1.73; 95% CI: 1.40-2.13 and HR: 2.05; 95% CI: 1.69-2.47, respectively). Even in the initial aortic valve replacement stratum, moderate/severe anemia was associated with significantly increased risk for the primary outcome measure (HR: 2.12; 95% CI: 1.44-3.11). Moreover, moderate/severe anemia was associated with significantly increased risk for major bleeding while under conservative management (HR: 1.93; 95% CI: 1.21-3.06). These results warrant further study to explore whether better management of anemia would lead to improvement of clinical outcomes.

OBJECTIVES: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR). METHODS: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50). RESULTS: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year. CONCLUSIONS: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy. TRAIL REGISTRATION NUMBER: UMIN000012140.

Aim: To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Methods and results: Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy. Conclusions: Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

Exercise stress testing has been widely undertaken for the diagnosis of heart diseases. The accurate assessment of clinical conditions can be conducted by comparing the findings obtained from the results of stress echocardiography with the changes in the blood/heart rate and electrocardiograms. Numerous overseas studies have reported the utility of stress echocardiography in diagnosing myocardial ischemia in Japan, the use of this modality for this purpose was included in the national health insurance reimbursable list in 2012. Nevertheless, stress echocardiography is far from being a widespread practice in Japan. This might be due to insufficient equipment (e.g., ergometers, space for test implementation) at each medical institution, shortage of technicians and sonographers who are well experienced and who are responsible for obtaining images during stress testing. The other possible reasons include the limited evidence available in Japan and the lack of a standardized testing protocol. Further dissemination of the practice of exercise stress echocardiography in this country is deemed necessary to establish satisfactory evidence for the use of stress echocardiography in the Japanese population. To this end, efforts are underway to develop a standardized protocol and report format to be adopted throughout Japan. We here present a guideline created by the Guideline Development Committee of the Japanese Society of Echocardiography that describes safe and effective stress echocardiography protocols and report formats. The readers are encouraged to perform exercise stress echocardiography using the proposed template for consensus document and report attached to this guideline.

Background: Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear. Methods and Results: From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF) No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction < 50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P< 0.001) and 20.7%, 33.8% and 52.3% (P< 0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64 95% confidence interval [CI]: 1.14–2.36, P=0.008 adjusted HR 1.47 95% CI: 1.03–2.11, P=0.03, respectively). Conclusions: AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

Background: The prevalence of atrial fibrillation (AF) is high in elder subjects. Our previous observational study suggested that vitamin K antagonist (VKA) promotes aortic valve degeneration, a principal cause of aortic stenosis in the elderly, and that angiotensin receptor blocker (ARB) attenuates its progression. This study aimed to prospectively investigate these observations in non-valvular AF patients. Methods: Of enrolled 430 patients with calcification on no or one aortic valve leaflet, all of the planned 4-year follow-up data were obtained in 122 non-valvular AF patients treated with warfarin (warfarin group) and 101 patients with cardiovascular diseases and without AF and prescription of warfarin (non-warfarin group). Results: Despite higher atherosclerotic risks in the non-warfarin group, 2 or 3 newly calcified leaflets emerged during 4 years in 18.0% of patients in the warfarin group and in 6.9% in the non-warfarin group (p = 0.014). Aortic valve area (AVA) did not significantly change in the non-warfarin group during the follow-up, but tended to decrease in the warfarin group (p = 0.057). Non-vitamin K antagonist oral anticoagulant got available in Japan after this study started, and warfarin was discontinued in 15 patients of the warfarin group. The reduction of AVA was significant in the remaining 107 patients on the continuous warfarin treatment (p = 0.002). The effects of ARB on AVA were obscure. Conclusion: Major bleeding associated with VKA is well recognized. This study suggests that the development of aortic valve degeneration is another risk of long-term use of VKA in non-valvular AF patients with no or mild aortic valve degeneration.

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both noncardiac factors (age, male, body mass index < 22, diabetes, prior history of stroke, dialysis, anemia, and malignancy) and cardiac factors (atrial fibrillation, ejection fraction < 68%, and the initial AVR strategy) were associated with non-cardiac death. These findings highlight the importance of close monitoring of noncardiac comorbidities, as well as HF and sudden death, to improve the mortality rate of severe AS patients.

Background: There is a paucity of data on the sex differences in the prevalence, clinical presentation, and prognosis of aortic stenosis (AS). Methods and Results: A total of 3,815 consecutive patients with severe AS were enrolled in the multicenter CURRENT AS registry between January 2003 and December 2011. The registry included 1,443 men (38%) and 2,372 women (62%). Women were much older than men (79 +/- 10 vs. 75 +/- 10 years, P<0.0001), and the ratio of women to men increased with age. The cumulative 5-year incidence of all-cause death was significantly higher in men than in women (47% vs. 41%, P=0.003), although women were more symptomatic and much older. The 5-year mortality was similar between men and women at age <65 years (16% vs. 15%, P=0.99), whereas it was significantly higher in men than in women at age >= 65 years (65-74 years, 38% vs. 19%, P<0.0001; 75-84 years, 55% vs. 34%, P<0.0001; >= 85 years: 82% vs. 72%, P=0.03). Conclusions: A large Japanese multicenter registry of consecutive patients with severe AS included a much higher proportion of women than men, with the female: male sex ratio increasing with age. The 5-year mortality rate of women was lower than that of men. Lower 5-year mortality rates in women were consistently seen across all age groups >65 years.

We have previously reported that a long-acting loop diuretic, azosemide, reduces cardiovascular risks in patients with chronic heart failure (CHF) as compared with a short-acting one, furosemide, in Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure (J-MELODIC). However, the mechanisms of the difference have not been elucidated. This study aimed to examine whether there is a difference in the reduction in plasma brain natriuretic peptide (BNP) level and in left ventricular (LV) functional recovery between the CHF patients treated with the long-acting diuretic (the azosemide group) and the short-acting diuretic (the furosemide group). We reviewed changes in plasma BNP level and echo-assessed LV functional parameters from baseline to a year after the entry in 288 CHF patients with New York Heart Association class II or III symptoms that joined J-MELODIC. The decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group (p < 0.01). The changes in echocardiographic parameters were not more favorable in the azosemide group than in the furosemide group. In conclusion, the decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group. These findings may account for the better prognosis in CHF patients treated with azosemide than those with furosemide in J-MELODIC.

Low blood flow velocity in the left atrial appendage (LAA) indicates a high risk of thromboembolism. Although transesophageal echocardiography (TEE) has been the standard method with which to evaluate the LAA blood flow velocity, a clinically noninvasive method is desired. We hypothesized that the ratio of the Hounsfield unit (HU) density at two distinct points within the LAA represents the blood flow velocity in the LAA. We retrospectively investigated 60 consecutive patients with atrial fibrillation (paroxysmal type, n = 29) who underwent enhanced computed tomography (CT) and TEE. The peak emptying flow velocity in the LAA (LAAPV) was evaluated using TEE. HU density was measured at proximal and distal sites of the LAA (LAAp and LAAd) on CT images. The LAAd/LAAp ratio was correlated with the LAAPV (P < 0.01, r = 0.69). Among several indices, the HU ratio was the most significant parameter associated with the LAAPV (beta = 0.469, CI 28.602-68.286, P < 0.001). Receiver-operating characteristic analysis (area under the curve, 0.91) demonstrated that an HU density ratio cutoff of 0.32 discriminated a low LAAPV (< 25 cm/s) with sensitivity of 90% and specificity of 84%. Flow velocity of the LAA can be estimated by the HU density ratio at distal and proximal sites within the LAA. Our method might be a feasible substitution for TEE to discriminate patients with a reduced LAAPV.

Background-There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS). Methods and Results-Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax >= 4.0 m/s and left ventricular ejection fraction = 50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 <= Vmax <4.5 m/s, N=550; group 2, 4.5 <= Vmax <5 m/s, N=279; and group 3, Vmax >= 5 m/s, N=246). Cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS-related events remained significant (hazard ratio, 1.39; 95% CI, 1.07-1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17-2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS-related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01-2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16-2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS-related events (interaction, P=0.88). Conclusions-In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS-related events. However, the cumulative 5-year incidence of the AS-related events remained very high even in asymptomatic patients with less greater Vmax.

Background There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm(2) with peak aortic jet velocity 4.0 m/s, and mean aortic pressure gradient 40 mm Hg. Methods and Results In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score-matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve-related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P<0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32-0.67; P<0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59; P<0.001). Conclusions The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140.

Objective The menstrual cycle-related changes in clinical laboratory values were analysed by use of data obtained in the Asian multicentre study aimed at derivation of common reference intervals for 85 major clinical laboratory tests. Methods Among 1876 healthy female volunteers, 893 had regular menstruation. They were classified into five groups according to dates between sample collection and the start of the last menstrual cycle: early follicular phase (1-6 days), late follicular phase (7-12 days), ovulatory phase (13-16 days), early luteal phase (17-22 days), and late luteal phase (23-31 days). Multiple linear regression analysis was performed to evaluate the menstrual cycle-related changes in test results. The magnitude was expressed as a standard deviation ratio of between-phase standard deviation to between-individual standard deviation based on nested ANOVA. Results Aside from obvious changes for four sex hormones (oestradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone), we observed statistically significant menstrual cycle-related changes in the following tests (standard deviation ratio >0.15): Na, Cl, creatine kinase, C-reactive protein, serum amyloid A, carbohydrate antigen 125, and parathyroid hormone were higher during the early follicular phase, while insulin, total cholesterol, and white blood cell were higher during the luteal phase. Significant associations of those test items with the four sex hormones were revealed. Conclusions The menstrual cycle-related changes in laboratory test results were revealed in some commonly tested items other than sex hormones. The findings are of interest in understanding female physiology in relation to hormonal changes, but the magnitude of changes is rather small and not very relevant in interpreting test results.

BACKGROUND Current guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS). OBJECTIVES The study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS. METHODS We used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm(2)) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score-matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report. RESULTS Baseline characteristics of the propensity score-matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively). CONCLUSIONS The long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140) (C) 2015 by the American College of Cardiology Foundation.

Background: Because of ethnic difference in the risk of degenerative aortic valve disease (DAVD), risk factors should be clarified in each race to establish prophylactic strategies for severe aortic valve stenosis (AS). Methods and Results: This study prospectively followed 359 Japanese subjects with DAVD and age >= 50 years for 3 years. As both patients with peak aortic transvalvular flow velocity >= 2 m/s and < 2 m/s were enrolled, subgroup analysis was also conducted. Most patients were under treatment for their comorbidities. The use of warfarin, but none of the traditional risk factors for atherosclerosis, was related to greater reduction in aortic valve area indexed to body surface area (iAVA). In patients with peak aortic transvalvular flow velocity < 2 m/s, the use of an angiotensin-receptor blocker (ARB) was associated with less decrease in iAVA. In patients with peak velocity >= 2 m/s, changes in iAVA were not related to any baseline characteristics, but peak velocity was less increased under treatment with an angiotensin-converting enzyme inhibitor (ACEI). Conclusions: In Japanese, the use of warfarin may exacerbate DAVD, and augmented management of atherosclerotic risk factors beyond the recommendations in the current guidelines is unlikely to exert additional benefit. The prescription of ARB for DAVD patients before the development of AS or ACEI after the development of AS may be useful.

BACKGROUND: Diuretics are the most prescribed drug in heart failure (HF) patients. However, clinical evidence about their long-term effects is lacking. The purpose of this study was to compare the therapeutic effects of furosemide and azosemide, a short- and long-acting loop diuretic, respectively, in patients with chronic heart failure (CHF). METHODS AND RESULTS: In this multicenter, prospective, randomized, open, blinded endpoint trial, we compared the effects of azosemide and furosemide in patients with CHF and New York Heart Association class II or III symptoms. 320 patients (160 patients in each group, mean age 71 years) were followed up for a minimum of 2 years. The primary endpoint was a composite of cardiovascular death or unplanned admission to hospital for congestive HF. During a median follow-up of 35.2 months, the primary endpoint occurred in 23 patients in the azosemide group and in 34 patients in the furosemide group (hazard ratio [HR], 0.55, 95% confidence interval [CI] 0.32-0.95: P=0.03). Among the secondary endpoints, unplanned admission to hospital for congestive HF or a need for modification of the treatment for HF were also reduced in the azosemide group compared with the furosemide group (HR, 0.60, 95%CI 0.36-0.99: P=0.048). CONCLUSIONS: Azosemide, compared with furosemide, reduced the risk of cardiovascular death or unplanned admission to hospital for congestive HF.

Trans-esophageal echocardiography < TEE> has been recognized as a standard procedure to exclude left atrial appendage thrombus < LAA-T> but it may cause discomfort in some patients. Multi-detector computed tomography < MDCT> may be performed to understand PV and LA anatomy as well as to detect LAA-T in patients with atrial fibrillation < AF> The purpose of this study is to determine whether TEE can be skipped before pulmonary vein isolation < PVI> by using MDCT.We enrolled 100 consecutive AF patients < paroxysmal AF in 73, persistent or long lasting AF in 27 > who underwent PVI. LAA-T was defined as well-contoured echogenic mass in LAA using TEE. To assess LAA by MDCT, the Hounsfield unit < HU> density was measured at LAA proximal < LAAp > and distal < LAAd> .The cutoff value of LAAp/LAAd to provide 100% probability of LAA-T absence was calculated using receiver operating characteristic curves R< OC-C> .LAA-T was detected in 7 patients < 7/27 patients with persistent or long lasting AF> . ROC-C indicates that LAAp/LAAd> 0.43 demonstrates 100% specificity. Using this cutoff value, 76% patients can be diagnosed as absence of LAA-T solely by MDCT In conclusion,LAA-T was observed only in persistent or long lasting AF patients.LAA-T can be excluded in 76% patients without using TEE. TEE could be unnecessary for PVI in PAF patients below the cutoff value of HU density. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Background: Postsystolic shortening is a sensitive maker of myocardial ischemia. The aim of this study was to investigate whether diastolic dyssynchrony imaging is useful for the objective interpretation of dobutamine stress echocardiography. Methods: Postsystolic shortening was detected by using tissue Doppler imaging displacement timing analysis: the delays of the displacement peaks from end-systole were displayed from green to red, depending on the preset time window on diastolic dyssynchrony imaging. Dobutamine stress echocardiography was performed in 59 patients with suspected coronary artery disease who presented with normal left ventricular wall motion at rest (age range, 44-83 years; 20 women). The optimal time windows for diastolic dyssynchrony imaging at rest and at peak dobutamine were determined by receiver operating characteristic analysis by measuring the delays of the displacement peaks in the left ventricular myocardial segments. Diastolic dyssynchrony imaging was performed using time windows of 100 msec at rest and 80 msec at peak dobutamine. The diagnostic power of diastolic dyssynchrony imaging was assessed with quantitative coronary angiography as the gold standard (>50% diameter stenosis) both at rest and at peak dobutamine. Results: Coronary artery disease was present in 37 patients (63%). Diastolic dyssynchrony imaging at peak dobutamine predicted the presence of coronary artery disease with sensitivity of 89%, specificity of 77%, predictive accuracy of 85%, positive predictive value of 79%, and negative predictive value of 81%. Diastolic dyssynchrony imaging at rest yielded sensitivity of 62%, specificity of 73%, predictive accuracy of 66%, positive predictive value of 79%, and negative predictive value of 53%. Importantly, diastolic dyssynchrony imaging demonstrated excellent intraindividual (97%) and interindividual (90%) agreement. Conclusion: Diastolic dyssynchrony imaging is useful in the objective interpretation of dobutamine stress echocardiography. (J Am Soc Echocardiogr 2010;23:1103-8.)

Calcific aortic valve disease (CAVD) is the most common etiology of acquired valvular heart disease, and hypertension is a principal underlying disease. The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis is a retrospective observational study to clarify the prognostic factors for progression of CAVD in Japanese. Data from 556 subjects who met the following criteria were analyzed: (1) >= 50 years old; (2) calcification in any aortic valve leaflet or peak aortic jet velocity >= 2 m s(-1) on an echocardiographic study performed between July 2004 and June 2007; and (3) availability of earlier echocardiographic data from within the previous 2-5 years to assess the progression of CAVD. The subjects were divided into two groups according to CAVD severity on the preceding echocardiographic examination. In early-stage subjects with calcification in one or zero leaflets who were without aortic stenosis on the preceding echocardiographic study (n=157), the prognostic factors for progression were the following: (1) no use of angiotensin receptor blockers (ARB) and (2) use of warfarin. In late-stage subjects with calcification in two or three leaflets and/or aortic stenosis on the preceding echocardiographic study (n=399), progression was observed in females and in subjects with low hemoglobin and a concentric left ventricle. There was no relation between medications and changes in CAVD. Prognostic factors for the progression of CAVD were different between the early and late stages. Initiation of ARB treatment during the early stage may be effective, and we should be vigilant about progression of CAVD in patients treated with warfarin. Hypertension Research (2010) 33, 269-274; doi:10.1038/hr.2009.225; published online 8 January 2010

We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. Introduction Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. Methods In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women >= 50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. Results Adjusted BIF-IMT values of subjects with spine T-score >=-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM >= 10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM >= 10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. Conclusion Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.

通常は小児期に診断されることが多い右室二腔症であるが,比較的高齢になるまで診断されず経過観察されていた症例を経験した.症例は62歳女性.小児期に心室中隔欠損症を指摘されていたが自覚症状はなかった.62歳時に初めて労作時の動悸,息切れを感じるようになり,当院受診し,うっ血性心不全の診断で入院となった.入院時の心臓超音波検査で,大きい欠損孔を有する心室中隔欠損症を認めた.また,経食道超音波検査で右室内に異常に発達した筋束により分かれる2つの腔を認め,その間に加速血流を認めた.心臓カテーテル検査では右室内に圧較差を認め,三尖弁側に位置する右室高圧腔で酸素飽和度の上昇を認めたため右室二腔症と診断した.肺動脈圧は30/12mmHgと正常範囲であり,右室内の筋束により肺動脈圧の上昇を抑制したことが心室中隔欠損を有していても高齢まで症状が乏しかった原因と考えられた.大きな欠損を伴う心室中隔欠損症であるにもかかわらず,自覚症状の乏しい例では,右室二腔症を念頭におき経食道超音波検査,心臓カテーテル検査等を追加し正確な診断をすることを考慮するべきである.

This is to demonstrate a new 2D-ultrasonographic technique which enabled clear resolution of deformed valves, visualization of venous reflux and quantitation of valve incompetence. In a 59-year-old Japanese female patient, ultrasonography was done using Aplio, Toshiba Medical Systems Co., Japan, equipped with 8 MHz linear probe capable of differential tissue harmonic imaging to diagnose the cause of her leg edema. Venous ultrasonography using this device at the popliteal venous valve in this patient demonstrated clear view of deformed venous valve and valve separation at one end of valvular agger while the other part of the valve is closed. Color Doppler failed to show venous reflux due to its low velocity. However, the appearance and disappearance of a thrombus-like echo could be imaged using 2D-ultrasonography. In addition, we were able to demonstrate the time-course change of valve opening and closing, and quantitate the valve incompetence using M-mode ultrasonography.

Background Diuretics are the most prescribed medication for heart failure (HF) patients, but clinical evidence of the long-term effects of diuretics are lacking. The present study was designed to compare the therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with HF to test the hypothesis that long-acting diuretics are superior therapy. Methods and Results The Japanese Multicenter Evaluation of LOng- vs short-acting Diuretics In Congestive heart failure (J-MELODIC) is a multicenter, prospective, randomized trial enrolling a total of 300 patients (150 patients in each group). The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive HF. Other outcomes include all-cause mortality, worsening of the symptoms of HF, or a need for modification of therapy. Serial assessment of echocardiographic and neurohumoral parameters will be conducted over a minimum follow-up period of 2 years. Conclusions The study results will provide important evidence for the treatment of chronic HF.

Hemochromatosis represents primary or secondary deposition of an excessive amount of iron in many tissues and organs in the body. Recent studies have evaluated regional myocardial function by tissue Doppler echocardiography. Myocardial strain imaging facilitates the evaluation of regional myocardial function without being influenced by cardiac rotation and translation. Several studies have reported the usefulness of myocardial strain and myocardial strain gradient imaging in patients with various myocardial diseases. In this paper, we performed myocardial strain imaging in a patient with secondary hemochromatosis. © 2007, Japanese Society of Echocardiography. All rights reserved.

Background. Assessment of deterioration of regional wall motion by echocardiography is not only subjective but also features difficulties with interobserver agreement. Progress in digital communication technology has made it possible to send video images from a distant location via the Internet. Objectives. The possibility of evaluating left ventricular wall motion using video images sent via the Internet to distant institutions was evaluated. Methods. Twenty-two subjects were randomly selected. Four sets of video images (parastemal long-axis view, parastemal short-axis view, apical four-chamber view, and apical two-chamber view) were taken for one cardiac cycle. The images were sent via the Internet to two institutions (observer C in facility A and observers D and E in facility B)for evaluation. Great care was taken to prevent disclosure of patient information to these observers. Parastemal long-axis images were divided into four segments, and the paraster-nal short-axis view, apical four-chamber view, and apical two-chamber view were divided into six segments. One of the following assessments, normokinesis, hypokinesis, akinesis, or dyskinesis, was assigned to each segment. The interobserver rates of agreement in judgments between observers C and D, observers C and E, and intraobserver agreement rate (for observer D) were calculated. Results. The rate of interobserver agreement was 85.7%(394/460 segments Kappa = 0.65)between observers C and D, 76.7%(353/460 segments Kappa = 0.39)between observers D and E, and 76.3% (351/460 segments Kappa = 0.36)between observers C and E, and intraobserver agreement was 94.3% (434/460 Kappa = 0.86). Segments of difference judgments between observers C and D were normoki-nesis-hypokinesis 62.1%, hypokinesis-akinesis 33.3%, akinesis-dyskinesis 3.0%, and normokinesis-akinesis 1.5%.

A 36-year-old male patient suffered recurrence of acute lymphocytic leukemia in May 2004. His fever did not decrease after hospitalization, despite continuous administration of antibacterial and antifungal agents, and echocardiography was therefore carried out. Numerous movable vegetations were attached to the mitral valve tendon. Histologic dissection showed vegetation comprising mainly Aspergillus, which uniformly covered the endocardium. When Aspergillus infects the heart, it causes abscesses in the myocardium but rarely causes infective endocarditis. We report finding huge vegetations of Aspergillus in the left ventricle. © 2007, The Japan Society of Ultrasonics in Medicine. All rights reserved.

冠動脈血流の検出率は超音波診断装置の技術進歩に伴い向上し,広く臨床の場で利用されている.そこで我々は虚血性心疾患の診断で入院し,冠動脈造影検査を施行し得た83例のうち左冠動脈前下行枝(LAD)の血流が経胸壁ドプラ法にて検出可能であった57例に対し,Handgrip test(HGT)を施行した.検出したLADの拡張期最大血流速(diastolic peak velocity : DPV),時間速度積分値(time velocity integral : TVI)のHGTによる増加率を求め,冠動脈造影にてLADに有意狭窄を持つS群と持たないN群とに分け比較検討した.両群において,心拍数,拡張期血圧,収縮期血圧はHGT後にはいずれも有意に増加を認めた(p<0.05).しかし,DPV, TVIはN群では有意な増加を認めたが,S群では認めなかった.N群,S群の両者において冠動脈造影検査施行後,LADの狭窄率とDPV, TVIの増加率を比較検討したところ,増加率のcut off値を1.2倍とすると,DPVは感度82.1%,特異度86.7%で,TVIは感度78.6%,特異度83.3%で70%以上の狭窄病変が診断できた.以上のことからHGT前後で経胸壁ドプラ法を用いて求めたLADのDPV, TVIの増加率から狭窄病変の診断が可能であると考えられた.

Background In Western countries, many studies have shown that among healthy people moderate drinkers have a lower incidence of cardiovascular events than abstainers and heavy drinkers. However, it is not clear whether this is true in patients with a healed myocardial infarction (MI). Methods and Results In the present study cardiovascular events were defined as cardiac events or strokes. Male patients only were included because the incidence of cardiovascular events is low in females. In patients younger than 65 years, the incidence of cardiovascular events was 34.6 persons per year (54 cases: 3.9%) of abstainers, 17.4 persons per year (20 cases: 1.9%) of moderate drinkers (p < 0.01 vs abstainers) and 30.3 s persons per year (18 cases: 3.2%) of heavy drinkers. However, in those aged 65 years or older, the incidence was 47.8 persons per year (24 cases: 4.5%) of abstainers, 58.4 persons per year (14 cases: 5.6%) of moderate drinkers, and 314.8 persons per year (12 cases: 19.7%) of heavy drinkers. In this age group, cardiovascular events were significantly higher in heavy drinkers than in the other 2 groups (p < 0.01), and the incidence was not lower in the moderate drinkers than in abstainers as shown in the younger group. Conclusions Inpatients younger than 65 years with a healed MI, drinking limited less than 30ml/day (moderate intake) reduces the incidence of cardiovascular events, but not in those aged 65 years or older.

近年心エコー図法において血液と心臓構造物との境界を自動認識するシステムが実用化され,本研究ではこの原理に基づいて,局所壁運動を客観的に評価するA-SMA(Automated segmental motion analysis)法を用いてエルゴメータ運動負荷心エコー図法施行時に,局所的な心筋虚血の定量的評価,有用性を検討した.対象は健康成人40例,狭心症25例,陳旧性心筋梗塞60例である.収縮性の指標としてFAC(fractionalarea change),PER(peak ejection rate),t-PERc(time to PER correct)を,拡張性の指標としてPFR(peak filling rate),t-PFRc(time to PFR correct),を用いた.狭心症例ではFAC,PERは非虚血部で有意に増大し,t-PERcは有意に短縮したが,虚血部では不変であった.PFRは非虚血部では有意に増大し,虚血部では軽度有意に増大した.t-PFRcは非虚血部では有意に短縮し,虚血部では有意に延長した.以上の結果よりエルゴメータ運動負荷心エコー図法において今までは左室の定量的壁運動評価は左室全体でしか評価できなかったが本研究では以上のごとく領域別に,しかもオンラインで評価可能であり再現性も高く,心筋虚血の定量的評価を行うことが可能であると結論された.

Background: Exercise echocardiography is an effective means of noninvasively detecting coronary artery disease (CAD), and hand-carried cardiac ultrasound (HCU) devices are now being used to diagnose CAD in emergency rooms and at bedsides. Objective: To compare the efficacies of exercise echocardiography with an HCU device (EchoCG-HCU) and exercise electrocardiography (ECG) in the diagnosis of CAD. Methods: Fifty-eight patients underwent symptom-limited treadmill exercise testing. Two-dimensional echocardiographic images were obtained from standard parasternal and apical windows at rest and immediately after exercise using an HCU device (180 PLUS SonoSite Inc, Bothell, Wash). Wall motion was scored for each of 16 left ventricular segments using a 5-point grading system. The development of new or worsening wall motion was considered to be indicative of ischemia. Results: When identifying CAD using exercise ECG, the sensitivity ws 63%, the specificity was 72%, and the diagnostic accuracy was 69%. By comparison, with exercise EchoCG-HCU the sensitivity was 68%, the specificity was 90%, and the diagnostic accuracy was 83%. Moreover, the specificity of exercise EchoCG-RCU was significantly higher than that of exercise ECG ( p <.05). Conclusion: Exercise EchoCG-HCU is at least as useful as exercise ECG for diagnosing CAD.

Ultrasound has become an important tool for diagnosing cardiac disease, used to produce echocardiographic images. Physicians can visually diagnose heart disease by observing the movements of the heart walls on the echocardiogram. But visual diagnosis requires a trained physician, and is a matter of subjective interpretation, so that there is a possibility of differences of opinion between physicians. Color kinesis is a new technique for displaying echocardiograms. In color kinesis, the position of the ventricular endocardium is measured from the strength of ultrasonic reflections at frequent intervals, and its position is shown in diffferent colors for each time slice. The echocardiogram generated by color kinesis, or the color kinesis image, can show in a single frame information on the movement of the ventricle walls from the beginning of a systole to the end. This is an effective way of diagnosing any abnormalities in the movement of the heart walls. In the investigation reported here we extracted the characteristics of the movements of the ventricular endocardium based on two color kinesis frames before and after administering a dobutamine load (to increase systolic force), and attempted to identify abnormalities based on the endocardium's movement characteristics before and after dosing. Identification was performed by a neural network. © 2006 Wiley Periodicals, Inc.

Background Although short-acting nifedipine does not prevent myocardial infarction (MI), calcium antagonists with a long half-life may be effective. Methods and Results The present study was a retrospective analysis of the incidences of cardiac events among patients with a healed MI treated with 3 times-a-day type nifedipine (half-life 1.8 h; n=617), twice-a-day type nifedipine (half-life 4.0 h; n=527) and those not taking calcium antagonists (n=1,593) from 1986 to 1993, and the incidences of those on once-a-day type calcium antagonists (half-life 11.0 h; n =903) and those not taking calcium antagonists (n=2,788) from 1994 to 2001. Cardiac events included cardiac death and nonfatal recurrent MI. Single and multivariate analyses using the Cox-Hazard model were performed. From 1986 to 1993 cardiac events occurred in 38 patients with 3-times-a-day nifedipine (6.2%, hazard ratio and 95% confidence interval: 1.45 and 0.93-2.27), in 18 patients with twice-a-day nifedipine (3.4%: 0.68 and 0.39-1.20), 57 patients without calcium antagonists (3.6%). Cardiac events also occurred in 11 patients with once-a-day type nifedipine (1.2%: 0.72 and 0.37-1.42) and 48 patients without calcium antagonists (1.7%). Of the once-a-day type calcium antagonists, cardiac events were the lowest (2 patients, 0.6%: 0.32 and 0.08-1.31) in patients with amlodipine (half-life 39.0 h; n=334), which has the longest half-life. None of these drugs were a significant factor in the increase or decrease in the incidence of cardiac events. However, there was a good correlation between the half-life of the calcium antagonist and the hazard ratio for reducing cardiac events. Conclusion Although there was a tendency toward a reduction in cardiac events using calcium antagonists with long half-life, none of these drugs could significantly reduce the incidence of cardiac events in patients with a healed MI.

The ventricular septum receives its blood supply from the septal perforators of the left anterior descending (LAD) coronary artery and the right coronary. artery. However, when the LAD artery extends to the inferior wall, beyond the apex (so-called wrapped LAD), the ventricular septum near the apex receives blood supply only from the LAD artery. As a consequence, ventricular septal rupture (VSR) would seem more likely in myocardial infarction with occlusion of this type of LAD artery. To test this hypothesis, we compared electrocardiographic findings in 21 patients who had anterior acute myocardial infarction that was complicated by VSR with those in 275 patients who had acute myocardial infarction that was not complicated by VSR. We observed ST-segment elevation in all inferior leads (II, III, and aVF) in addition to anterior leads in 42.0% of patients (9 of 21) who had VSR but in only 3.6% of those (10 of 275) who did not have VSR. Abnormal Q waves appeared in all 3 inferior leads in 44.4% of patients (8 of 18) who had VSR but in only 4.0% of those (10 of 250) who did not have VSR. Thus, the incidence of ST-segment elevation and abnormal Q waves in the inferior leads was significantly (p < 0.001) greater in the VSR group. In addition, multivariate analysis of patient characteristics, including advanced age, female gender, and coronary morphology, showed VSR to be significantly correlated with ST-segment elevation (odds ratio 16.93, 95% confidence interval 4.13 to 6930) and abnormal Q waves (odds ratio 13.64, 95% confidence interval 3.16 to 58.79) in the 3 inferior leads. In conclusion, these electrocardiographic findings can be useful predictors of complication by VSR. (c) 2005 Elsevier Inc. All rights reserved.

64歳男.広範前壁急性心筋梗塞にてCCU入院となり,発症約3時間後に改変型組織プラスミノーゲンアクチベータ(モンテプラーゼ)137.5万単位を1分間かけて静脈内投与した.発症後4時間の冠動脈造影検査では左冠動脈前下行枝セグメント7が99%狭窄でTIMI3血流に再開通し,ステント留置術を追加した.投与9時間後から呼吸困難が出現し,約200mlの喀血に引き続き低酸素血症をきたしたため,気管内挿管し呼吸管理を行った.胸部X線像にて両肺野に広範な浸潤影を認め,気管支鏡では各気管支からのびまん性出血が確認され,肺疾患の既往がなくアレルギー反応も認めないことから,血栓溶解薬によるびまん性肺出血と診断した.トロンビン末2000単位の散布による止血後は一時浸潤影の改善を認めたが,著明な肺胞低換気・高炭酸ガス血症の遷延化により第113病日に死亡した.両肺の剖検による病理組織学的所見では肺胞中隔にびまん性の線維性肥厚・肺胞腔にヘモジデリンを貪食したマクロファージの浸潤が認められた

Purpose. The aim of this study was to develop a method for early, accurate differentiation between old myocardial infarction (OMI) and angina pectoris (AP) using color kinesis (CK) images. We first extracted exact end-diastolic and end-systolic contours from CK images and then extracted the features of cardiac function from two CK images (one at rest, the other after exercise) and investigated their effectiveness in differentiating old myocardial infarction and angina pectoris. We then evaluated the effectiveness of several features in recognizing coronary artery disease and used the effective features to show the differentiation results. Methods. First, we extracted exact end-diastolic and end-systolic contours from CK images with an active contour model. Second, we defined the features that seemed to be effective in recognizing coronary artery disease. The features are extracted from the region between the end-diastolic endocardial contour and end-systolic endocardial contour in two CK images: one obtained when the subject was at rest and the other after exercise. Nine features were considered effective for differentiating old myocardial infarction and angina pectoris, and the effectiveness in recognizing coronary artery disease, which includes old myocardial infarction and angina pectoris, was evaluated. Third, coronary artery disease is recognized by the effective features. Results. Contours near a manual trace by a skilled physician were obtained using the proposed method. Multiple comparisons of the mean values of the extracted features were drawn among three groups: a healthy-subject group an old myocardial infarction patient group and an angina pectoris patient group. The feature effective in differentiating old myocardial infarction was the "area at rest" those effective in differentiating angina pectoris were a "decrease in area" and a "decrease in movement." These effective features have almost always differentiated old myocardial infarction and angina pectoris. Conclusions. This study used the endocardial contour extraction technique with the dynamic contour model and evaluated the validity of the features of cardiac function it then recognized coronary artery disease from the effective features. Multiple comparisons of the mean value of the extracted features among the healthy-subject group, the old myocardial infarction patient group, and the angina pectoris patient group has proved that the "area at rest" is effective in differentiating old myocardial infarction, and the "decrease in area" and "decrease in movement" are effective for differentiating angina pectoris. © The Japan Society of Ultrasonics in Medicine 2005.

Background Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. Methods and Results A total of 1,247 patients admitted to Kinki University School of Medicine within 24h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p < 0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p < 0.01). This decrease was particularly marked among those admitted within 6h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p < 0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. Conclusions Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death.

Color Kinesis画像を用いた心機能定量解析のための心内膜輪郭抽出において,動的輪郭モデルを用いた輪郭抽出手法を提案し,医師のマニュアルトレース及び従来手法と定量的比較を行うことで提案手法の有効性を示す.

Objectives. Cardiac catheterization is increasingly used for the diagnosis or treatment of coronary artery disease. Previous studies that revealed the incidence of complications such as arteriovenous fistula and pseudoaneurysm were based on retrospective analysis of cohorts referred to vascular surgery. This study was designed to determine the incidence of arteriovenous fistula and pseudoaneurysm after percutaneous transluminal angiography. Methods. All 557 consecutive patients undergoing cardiac catheterization were examined by ultrasonography from March 1, 2001 to April 1, 2002, to investigate the occurrence of arteriovenous fistula and pseudoaneurysm at the puncture site. Results. Pseudoaneurysm was found in 16 patients (2.9%), and arteriovenous fistula in 12 patients (2.2%). Pseudoaneurysm in 7 patients (43.8%) and arteriovenous fistula in 6 patients (50.0%) were diagnosed only by ultrasonic examination. There were more female patients (9 patients, 56.3%) than male with pseudoaneurysm (p < 0.01). The puncture site was located after the division of the deep femoral artery and superficial femoral artery in all patients with complications. Conclusions. Ultrasonic examination was useful for diagnosis of complications such as arteriovenous fistula and pseudoaneurysm after cardiac catheterization.

Background Although the favorable effects of beta-blockers in the treatment of myocardial infarction (MI) have been repeatedly demonstrated in Western countries, administration of this drug has been limited in Japan. Methods and Results The study group of 1,896 patients with MI was retrospectively divided into 1,029 patients treated by beta-blockers and 867 not treated by beta-blockers, and the incidences of cardiac events, consisting of recurrent MI, death because of worsening heart failure, and sudden death, and cardiovascular events, comprising cardiac events and stroke, were compared in both groups. There were 45 cardiac events (4.4%, 30.1 patients/ 1,000 patients (.)year) among the g-blocker group, which was significantly less than the 56 cardiac events (6.5%, 52.3 patients/ 1,000 patients (.)year) among the no-g-blocker group (p<0.05). The total mortality was 92 (8.9%, 61.6 patients/1,000 patients-year) and 124 (14.3%, 115.8 patients/1,000 patients-year), respectively, and cardiac death occurred in 42 (4.1%, 28.1 patients/1,000 patients-year) and 53 (6.1%, 49.5 patients/1,000 patients-year), respectively, indicating that both these events occurred significantly less in the g-blocker group (p<0.01 and p<0.05). Conclusions Beta-blockers prevent cardiac events in Japanese patients with MI. However, a placebo-controlled, double-blind, multicenter, clinical trial conducted on a large scale in Japan would further contribute more precise information of the useful effects of g-blockers.

近年,医学の分野では心疾患の診断に超音波を用いて心臓を映した超音波心エコー画像が使われている.現在,医師の目測により超音波心エコー画像から心筋壁の動きを読み取り心疾患の診断を行っている.しかし,目測による診断には訓練された医師が必要であり,更に医師の目測は主観的に行われるため個人差が生じる.超音波心エコー画像の新しい表示法の一つにColor Kinesis法がある. Color Kinesis法は超音波の反射波強度から各時刻ごとの心室内膜の位置を推定し,その位置を異なった色で表現する表示法である. Color Kinesis法により得られた超音波心エコー画像(Color Kinesis画像)は,1枚の画像の中に収縮初期から収縮末期までの心室内膜の動きの情報を含んでおり,心室壁運動異常の診断に有効である.本論文では,ドブタミン負荷(心収縮力増強負荷)試験前後の2枚のColor Kinesis画像から心室内膜の動きの特徴を抽出し,負荷前後での心室内膜の動きの特徴から壁運動異常の有無及びその領域の識別が可能であるか否かを検討する.識別にはニユーラルネットを用いる.

慢性心不全に対する治療法としてアンジオテンシン変換酵素阻害薬(ACE-1)とアンジオテンシンIIタイプ1(AT1)受容体ブロッカー(ARB)の併用療法における有効性が最近示されつつある.ACE-IとARBの併用が心機能,特に心臓交感神経機能及び神経体液因子に対する影響を詳細に検討することにより,慢性心不全の新たな治療戦略が確立できると思われる.そこで本研究では左室駆出率40%以下の慢性心不全患者におけるACE-1単独療法群(単独群:15症例)とACE-1とARBの併用療法群(併用群:15症例)の心機能に対する影響を経時的に検討した.心エコー図法における左室駆出率(EF),血中脳性ナトリウム利尿ペプチド(BNP)は併用群で投与1か月後に改善が認められ(EF:38.9±10.1 vs 45.1±12.8%,p<0.05,BNP:363.4±279.8 vs 121.4±115.3pg/ml,p<0.001),単独群の改善に先行した(EF:43.7±10.8 vs 47.5±11.6,NS,BNP:313.1±300.3 vs 173.4±177.8,NS).血中インターロイキン6は併用群でのみ投与6か月後に有意に低下した(2.39±2.23 vs 1.04±0.93pg/ml,p<0.05).^<122>I-metaiodobenzylguanidine(MIBG)心筋シンチグラムにおける心臓/上縦隔^<123>I-MIBG集積比の後期像(後期H/M比)とその洗い出し率(%washout rate : %WR)は併用群においてのみ投与6か月後で有意に改善した(後期H/M比:1.74±0.21 vs 1.95±0.29,p<0.05,%WR:30.6±10.1 vs 19.2±6.3%,p<0.05).血中アルドステロン(Ald)は併用群でのみ有意に低下し(138.2±78.0 vs 81.9±23.4ng/dl,p<0.01),単独群では上昇傾向にあった(102.3±62.3 vs 122.0±70.4ng/dl,NS).特に併用群においてAld減少群の方がBNP減少率,後期H/M比改善率も有意に大きかった.以上より慢性心不全に対するACE-1とARBの併用療法はACE-1単独療法に比し心機能改善に関してより有用である事が明らかとなり,その機序としてAldの低下が重要な役割を果たしていると推測された.

The aims of this study were to compare exercise-induced ST-segment elevation with and without ischemia and to examine the relation between exercise-induced ST-segment elevation and the location of myocardial ischemia. Seventy-nine patients with first anterior myocardial infarction underwent thallium-201 exercise myocardial scintigraphy test one month after myocardial infarction. There were 37 patients showing no reversible defect (non ischemia group), 33 with reversible defect in the territory of the left descending coronary artery (homozonal ischemia group) and 9 with a reversible defect in the territory of the left circumflex or right coronary artery (remote ischemia group). There were no significant differences among the three groups with respect to infarct size, presence of dyskinesis and exercise endurance time. Patients with homozonal ischemia had the highest degree of ST-segment elevation (0.22+/-0.09 mV) followed by patients Without ischemia (0.13+/-0.07 mV) and those with remote ischemia (0.09+/-0.08 mV, P<.01). In conclusion, Myocardial ischemia adjacent to infarction amplifies exercise-induced ST-segment elevation.

A 74-year-old man was admitted to our hospital complaining of dyspnea. Parasternal transthoracic echocardiography showed a quadricuspid pulmonary valve above the aortic valve and a hypoplastic accessory cusp between the right and left cusps of the pulmonary valve. The pulmonary valve ring diameter was normal (26 mm) but the transvalvular peak velocity was 3.5 m/sec, suggesting a pressure gradient of 49 mmHg across the pulmonary valve. The pulmonary valve had thickening and decrease in mobility of the leaflets without complete closure during diastole, and severe pulmonary regurgitation was present. Heart failure was treated successfully with digitalis and diuretics. Quadricuspid pulmonary valve is difficult to identify using transthoracic echocardiography because of the anatomical features. In this case, the dilated main pulmonary artery caused the pulmonary valve orifice to shift anteriorly, allowing visualization of the short-axis view of the pulmonary valve.

症例は50歳, 男性.39歳の時, 突然意識を消失し当院へ救急搬送された.搬送時のモニター心電図では心室頻拍がみられていたがリドカインを静注し洞調律に復帰した.洞調律復帰後の12誘導心電図, 心エコー所見, また血液生化学検査上, 異常が認められないことから陳旧性心筋梗塞が疑われ心臓カテーテル検査を行った.冠動脈造影では左前下行枝近位部に完全閉塞が認められた.左回旋枝には高度狭窄とその末梢に直径4.9mmの冠動脈瘤(Quantitative Coronary Arteriography;QCAにより測定)が認められた.また右冠動脈には最大径5.8mmの拡張性病変(QCAにより測定)が認められた.その後経過は良好であったが11年後の50歳時, 再び心室頻拍を生じ入院となり, 心臓カテーテル検査を行った.冠動脈造影上左冠動脈前下行枝近位部の完全閉塞, および回旋枝の高度狭窄には変化が認められなかったが, 回旋枝の冠動脈瘤は直径4.3mm(QCAにより測定)と若干の縮小が認められた.右冠動脈造影では拡張性病変が最大径4.8mm(QCAにより測定)と一部に改善が認められた.川崎病患者で小児期から若年期までの長期経過の報告は今までに多数あるが成人後の長期経過の報告は我々の知るところではない.本症例は成人になり川崎病後遺症と考えられる冠動脈病変が発見された1例で, 11年の経過を観察したので報告する.

Objectives. We assessed the usefulness of hyperventilation and cold-pressor stress echocardiography in the diagnosis of vasospastic angina compared with that of iodine-123 metaiodobenzylguanidine (I-123- MUBG) myocardial scintigraphy. Background. Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in the diagnosis of vasospastic angina. I-123-MIBG images and stress echocardiography have recently been proposed as a useful tool for detecting vasospastic angina. Method. Thirty patients (21 males and 9 females, mean age: 52 +/- 14 years) who complained of rest angina were enrolled for this study. The hyperventilation and cold-pressor stress echocardiography test consisted of hyperventilation for 6 minutes, followed by cold water pressor for 2 minutes under continuous electrocardiographic and echocardiographic monitoring. Left ventricular regional waft motion by echocardiogram was analyzed by using the 16-segment model, and wall motion ranging from normokinesis to dyskinesis was evaluated visually in each segment. Single-photon emission computed tomography images of I-123-MIBG myocardial scintigraphy were divided into 26 segments. Defect scores were established using the 4 grades. The echocardiographic criteria for coronary spasm was worsening wall motion and the scintigraphic criteria was defect score more than moderately reduced. Acetylcholine was selectively injected into the right coronary artery (20 mug and 50 mug) and left coronary artery (20 mug, 50 mug, and 100 mug). Results. Of 30 patients, 20 patients had coronary spasm on coronary angiography with an intracoronary injection of acetylcholine, whereas 10 patients showed no spasm. Multivessel spasms were observed in 15 patients. Sensitivity, spe(c)ificity, positive predictive value, negative predictive value, and diagnostic accuracy of hyperventilation and cold-pressor stress echocardiography for diagnosing in patients with vasospastic angina were 90%, 90%, 95%, 82%, and 90%, respectively. However, those of I-123- MIBG myocardial scintigraphy for diagnosing in patients with vasospastic angina were 90%, 40%, 75%, 67%, and 73%, respectively. The specificity of hyperventilation and cold-pressor stress echocardiography was significantly higher than that of I-123- MIBG myocardial scintigraphy (P <.05). Conclusion: The specificity of hyperventilation and cold-pressor stress echocardiography in diagnosing coronary spasm were higher than that shown by I-201-MIBG myocardial scintigraphy.

Stress-induced ST-segment elevation following myocardial infarction (MI) has been correlated with myocardial ischemia, viability and wall motion abnormality, but its mechanism is still unclear, so the present study compared ST-segment elevation and wall motion response during exercise, dobutamine and dipyridamole stresses. Twenty-five patients with their first anterior MI underwent exercise, dobutamine and dipyridamole echocardiography on different days 4-6 weeks after MI. Left ventricular wall motion was analyzed using 5-grade/16-segment model and myocardial ischemia was considered as a worsening of the wall motion score index (WMSI) during the stress test; myocardial viability was defined as a reduction of WMSI during low dose dobutamine. Dyskinesis formation was defined by visual analysis as akinesis that became dyskinetic or if the dyskinesis worsened. Both exercise and dobutamine induced ST-segment elevation, but dipyridamole did not. There was no significant difference in the degree of ST-segment elevation between the patients with and without myocardial ischemia or dyskinesis formation. Exercise induced a higher ST-segment elevation in patients with myocardial viability than those without (0.17 +/-0.09 mV vs 0.09 +/-0.07 mV, p <0.05). Exercise-induced ST-segment elevations correlated with dobutamine-induced ST-segment elevations (p <0.01), changes in heart rate (p <0.05) and systolic blood pressure (p <0.05). In conclusions, stress-induced ST-segment elevation does not correlate with either myocardial ischemia or stress-induced dyskinesis, but may be associated with myocardial viability.

Kinki University School of Medicine introduced clerkships for undergraduate clinical training in 1999. Clinical clerkships are performed for the first 8 weeks of the sixth academic year. In 1999 and 2000 we conducted questionnaire surveys asking students about this system. The teaching staff encourages students to participate extensively in clinical situations, which reflects the consensus about this system. We also performed similar surveys of nurses and teaching staff. Clinical clerkships did not increase the incidence of problems between patients and medical staff. Many students felt their motivation to be a physician was increased. Although the findings of these questionnaire surveys indicate that our clerkship system works successfully, they also revealed some problems for sixth-year students. Although we recognize the significance of this system for undergraduate clinical training, further improvement is required.

We report the usefulness of 2-dimensional echocardiography during the cold-presser test immediately after hyperventilation for noninvasive diagnosis of coronary vasospasm in 43 patients with suspected vasospastic angina. The stress test consisted of hyperventilation for 6 minutes, followed by cold mater presser stress for 2 minutes under continuous electrocardiographic and echocardiographic monitoring. Coronary angiography with an intracoronary injection of acetylcholine was performed within 2 weeks after the stress test. Coronary spasm was observed in 33 patients by angiography. Multivessel spasm was diagnosed in 26 patients by stress echocardiography and in 23 patients by angiography. The stress-induced mall motion abnormalities occurred earlier than the ST-segment changes and chest pain. The wall motion abnormalities shown on the echocardiogram correlated well with the vascular territories of the coronary artery that had the spasm. The sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-presser stress echocardiography for detecting vasospastic angina against coronary angiography with an intracoronary injection of acetylcholine were 91%, 90%, and 91%, respectively. However, the sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-presser stress electrocardiography for detecting vasospastic angina were 48%, 100%, and 60%, respectively. No major side effects were observed during or after the stress test. Echocardiographic monitoring during the stress test detected spasm unaccompanied by either ST-segment changes or chest pain and revealed the location of multivessel coronary spasm. Hyperventilation and cold-presser stress echocardiography is thus a noninvasive and useful tool for the diagnosis of vasospastic angina.

To assess the ability of the proximal isovelocity surface area (PISA) method to accurately measure the stenotic mitral valve area (MVA), and to assess whether aortic regurgitation (AR) affects the calculation, we compared the accuracy of the PISA method and the pressure half-time (PHT) method for determining MVA in patients with and without associated AR by using two-dimensional echocardiographic planimetry as a standard. The study population consisted of 45 patients with mitral stenosis. Seventeen of the 45 patients had associated moderate-to-severe AR. The PISA method was performed using low aliasing velocity (AV) of 10% of the peak transmitral velocity, which provided the most accurate estimation of MVA when compared with planimetry. The maximal radius r of the PISA was measured from the orifice to blue-red aliasing interface. Using the PISA method, MVA was calculated as (2 pir(2)) x theta / 180 x AV/Vmax, where theta was the inflow angle formed by mitral leaflets, AV was the aliasing velocity (cm/sec), and Vmax: was the peak transmitral velocity (cm/sec). MVA by the PISA method correlated well with planimetry both in patients with AR (r = 0.90 P < 0.001, SEE = 0.17 cm(2)) and without AR (r = 0.92, P < 0.001, SEE = 0.16 cm(2)). However, MVA by the PHT method did not correlate as well with planimetry (r = 0.57, P < 0.05 SEE = 0.37 cm(2)) in patients with associated AR, and the PHT method produced a significant overestimation (24%) of MVA obtained by planimetry in these patients. We conclude that the PISA method allows accurate estimation of MVA and is not influenced by AR.

Objectives. Suboptimal endocardial definition reduces the diagnostic value of stress echocardiography for coronary artery disease, but intravenous infusion of a left ventricular contrast agent (Albunex®) may enhance endocardial border delineation and improve the diagnostic value of dobutamine stress echocardiography. Methods. Fifty-six patients, 38 with myocardial infarction, 16 with angina pectoris and two normal subjects, were enrolled in this study. Dobutamine was infused in scalar doses of 5 to 40 μg/kg/min. Intravenous infusion of Albunex (0.15 ml/kg) was administered at rest and during peak dobutamine stress during monitoring of the apical four-chamber view. The left ventricle in the apical four-chamber view was divided into six segments and an endocardial delineation score of 0 to 3 (none to excellent visualization) was given to each segment. Results. Endocardial delineation score was increased after Albunex infusion from 2.0 to 2.3 in the basal-septal, 2.0 to 2.4 in the mid-septal, 1.1 to 1.8 in the apical-septal, 0.7 to 1.2 in the apical-lateral, 0.9 to 1.6 in the mid-lateral, and 1.2 to 1.9 in the basal-lateral segments during peak dobutamine administration. Endocardial border resolution in the lateral wall showed greater improvement than in the septal wall after Albunex infusion. Diagnostic values in the left anterior descending artery territory failed to improve with Albunex infusion (sensitivity 82% to 89%, specificity 94% to 89%, and accuracy 86% to 89%), whereas a higher diagnostic accuracy was noted in the left circumflex artery territory with Albunex compared to without Albunex (sensitivity 63% to 81%, specificity 88% to 98%, and accuracy 80% to 93%, p < 0.05). Conclusions. Contrast agent improves the diagnostic accuracy of dobutamine stress echocardiography in the left circumflex artery territory.

Background. Stress echocardiography is an established clinical testing method and is accurate for the detection of coronary artery disease. Despite its widespread use, the safety of stress echocardiography has not been sufficiently documented in Japanese laboratories. Objectives. The feasibility, safety, complications and side effects of stress echocardiography were assessed for detecting myocardial ischemia in patients with suspected coronary artery disease. Methods. 1,866 patients who underwent dobutamine echocardiography (n = 897), exercise echocardiography (n = 722), and dipyridamole echocardiography (n = 247) were prospectively studied from November 1990 to April 2000. Dobutamine was administered intravenously at 5, 10, 20, 30, 40 μg/kg/min in 3-minute intervals. Exercise echocardiography used the supine ergometer, starting at 50 W and increasing gradually by 25 W at 3-minute intervals to the maximum of 150 W. Dipyridamole was administered intravenously at 0.14 mg/kg/min for 4 min. After a 4-minute observation period, the drug was re-administered at the same dose for 2 min. Results. The most common side effects under each stress were ventricular premature beats in 34.1% (dobutamine echocardiography), ventricular premature beats in 14.4% (exercise), and headache in 24.3% (dipyridamole). Serious side effects occurred in one patient (0.05%). The case of acute myocardial infarction was caused by dipyridamole echocardiography, and the patient needed emergency coronary angioplasty. Seven patients needed other drug therapy for nonsustained ventricular tachycardia (one), paroxysmal supraventricular tachycardia (two), sinus bradycardia (three), and bronchial asthma (one). There was no incidence of death, shock, or ventricular fibrillation, sustained ventricular tachycardia or other conditions requiring inpatient observation during stress echocardiography. Conclusions. Stress echocardiography is a reasonable, safe method for determining myocardial ischemia, but may be associated with minor, self-limiting side effects.

冠攣縮性狭心症疑いの患者43例に断層心エコー法を併用して過換気負荷と寒冷昇圧負荷を行い, 攣縮冠動脈の診断に有用か否か検討した.負荷心エコー法は過換気を6分間行った後, 2分間の寒冷昇圧を施行し, 12誘導心電図, 血圧は1分毎に記録し, 断層心エコーは連続的に観察した.攣縮冠動脈のゴールデンスタンダードとしてアセチルコリン負荷冠動脈造影検査を負荷心エコー法施行後1週間以内に行った.アセチルコリン負荷冠動脈造影において冠攣縮陽性は33例(77%), 負荷心エコー法では31例(72%)で壁運動異常が出現した.壁運動異常は心電図変化や胸痛より有意に早期に出現した.壁運動異常は心電図変化や胸痛の出現しなかった17例においても出現した.多枝冠攣縮は負荷心エコー法では74%(23例/31例), アセチルコリン負荷冠動脈造影では79%(26例/33例)に診断できた.アセチルコリン負荷冠動脈造影と過換気寒冷昇圧負荷冠動脈造影を施行できた症例で左前下行枝の93%(26枝/28枝), 左回旋枝の72%(13枝/18枝), 右冠動脈の65%(15枝/23枝)は冠動脈造影での攣縮冠動脈の灌流領域と負荷心エコー法での壁運動異常の出現部位が一致した.負荷心エコー法における冠攣縮診断の感度, 特異度, 正診率はそれぞれ78%, 85%, 81%であった.負荷心エコー法において重篤な副作用の出現はなかった.以上より過換気寒冷昇圧負荷心エコー法は心電図変化や胸痛の出現しない症例でも冠攣縮性狭心症を診断でき, また多枝冠攣縮の診断も可能であった.過換気寒冷昇圧負荷心エコー法は非観血的に繰り返し施行できるため, 冠攣縮性狭心症の診断にきわめて有効な検査法になり得ると考えられる.

This study determined whether the diagnosis of myocardial viability could be established on the basis of the contractile reserve during low level exercise with an ergometer using echocardiography. The study involved 22 patients with transmural old myocardial infarction who underwent exercise echocardiography, followed by coronary intervention after a mean 4 days. Exercise echocardiography was started from 50W and stepped up by 25W every 3 min up to a maximum of 150W. Low level exercise was administered for 1 to 2 min at 50W. A 16-segment model was used for the left ventricular wall motion, which was evaluated by five-grade scoring, ranging from normokinesis to dyskinesis. If patients showed improvement by one point or more in the score for segments of dyskinesis, akinesis, or severe hypokinesis on the exercise echocardiography, they were considered to have positive viability. The golden standard for the diagnosis of myocardial viability was that wall motion abnormalities before exercise echocardiography should be improved by one point or more after coronary intervention. Before exercise echocardiography, there were 152 segments showing wall motion abnormalities assessed as severe hypokinesis or more. After coronary intervention, improvement of the wall motion by one grade or more was found in 2 of the 18 segments (11%) for dyskinesis, in 38 of the 96 segments (40%) for akinesis, and in 22 of the 38 segments (58%) for severe hypokinesis improvement for the segments of severe hypokinesis was significantly better than those for dyskinesis and akinesis. Out of 19 segments with akinesis before exercise echocardiography in which wall motion was improved during low level exercise, 16 segments (84%) showed improvement in wall motion after coronary intervention. Out of 77 segments with akinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 22 segments (29%) showed improved wall motion after coronary intervention. There were 38 segments with severe hypokinesis before exercise echocardiography out of 12 segments in which wall motion was improved during low level exercise, 7 segments (58%) showed improved wall motion after coronary intervention. Out of 26 segments with severe hypokinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 11 segments(42%) showed improved wall motion after coronary intervention. Wall motion was improved after coronary intervention in 20 of 25 segments (80%) that showed the biphasic response, in 4 of 7 segments (57%) that showed improvement, in 14 of 43 segments (33%) that showed worsening, in 24 of 77 segments (31%) for no change the biphasic response showed a significantly higher improvement compared to worsening or no change. If segments in which wall motion was improved during low level exercise are regarded as positive viability segments, occurrences of the sensitivity, specificity and diagnostic accuracy of myocardial viability were 50%, 84%, and 71%, respectively. The diagnosis of myocardial viability by echocardiography under the administration of low level exercise has high specificity but low sensitivity.

A 58-year-old man was involved in an automobile accident and suffered remittent fever, leukocytosis and high C-reactive protein level. He developed a diastolic murmur 2 months after the accident. Transesophageal echocardiography showed severe aortic regurgitation with a vegetation-like echo image attached to the right coronary cusp leaflet, suggesting infective endocarditis. Intensive medical treatment for 11 months did not improve the vegetation-like echo-image, so aortic valve replacement was performed. Disruption of the right coronary cusp leaflet was confirmed surgically. Prolapse had occurred as a result of disruption during diastole. The vegetation-like echo-image was considered to be the tip of this leaflet.

左室局所壁運動異常を有する虚血性心疾患症例において, 血行再建術後の左室収縮機能の回復可能性(viability)を, 術前に検出できれば臨床的に極めて有用である.本研究では, ドブタミン負荷心エコー法(DSE)による心筋のviabilityの評価を目的として, 冠血行再建術前と術後早期にDSEを施行し, 術後の壁運動の改善時期との関係について検討した.対象は安静時に左室壁運動異常がある陳旧性心筋梗塞24例, 労作性狭心症7例, 総計31例である.DSEは血行再建術直前と術後1週以内に施行し, 安静時左室壁運動の評価は断層心エコー図で術直前, 術後1週以内, 術後平均5.5カ月に行なった.低容量ドブタミン負荷で壁運動が改善するものを陽性とした.術後早期の壁運動改善は12例, 5.5カ月後の術後晩期壁運動改善が8例, 残る11例は壁運動は改善しなかった.早期壁運動改善例で断層心エコー図上の各分画での術前低容量DSEの陽性率(感度)は90%であった.晩期壁運動改善例では術前低容量DSEの陽性率38%, 術後早期低容量DSEの陽性率88%と有意に後者の感度が高かった(p<0.01).壁運動非改善群での術前低容量DSEの陰性率(特異度)は90%, 術後の低容量DSEのそれは96%といずれも高値であった.術前DSEでの壁運動の反応として早期壁運動改善では29分画中, biphasic response(低容量DSEで壁運動が改善し高容量DSEで悪化するもの)26分画(90%), worsening(壁運動が改善することなく悪化するもの)3分画(10%)であった.それに対し, 晩期壁運動改善では16分画中, biphasic responseは6分画(38%)と少なく, それ以外のworseningとno change(壁運動不変)が合計10分画(62%)と多く, 改善時期によって術前DSEの反応性に有意な(p<0.01)偏りがあった.以上, 血行再建術後の壁運動改善は早期に起こるものと晩期に起こるものがあった.早期改善群は術前DSEの感度は高値であった.晩期改善では術前DSEの感度は低かったが, 術後早期DSEで88%が陽性となったことからhibernating myocardiumの中にstunned myocardiumの混在の可能性があると考えられた.

The objective of the present study was to assess the diagnostic values of three stress echocardiography tests ; exercise, dobutamine and dipyridamole, for the detection of myocardial ischemia. We performed exercise (supine ergometer), dobutamine (40 μg/kg/min), and dipyridamole (0.84mg/kg over 10min) stress echocardiography testings on 384 patients. Two-dimensional echocardiographic images were digitized and assigned in a quad-screen format for nonbiased interpretation. The image quality score index (IQSI) was the sum of the image quality scores of all views. All patients underwent coronary arteriography. Significant coronary artery disease was defined by ≩75% stenosis of the large coronary arteries. Sensitivity of exercise, dobutamine and dipyridamole echocardiographies was 89%, 83% and 80%, respectively. Specificity was 75%, 81% and 94%, respectively. Diagnostic accuracy was 86%, 83% and 83%, respectively. The sensitivity for one vessel disease tended to be slightly lower with dipyridamole echocardiography. IQSI during stress echocardiography was highest for dipyridamole followed by that of dobutamine and exercise. There were no significant differences in the sensitivity, specificity, and diagnostic accuracy between exercise ^<201>Tl myocardial scintigraphy, and the three stress echocardiography methods. In the present study, exercise, dobutamine and dipyridamole echocardiographies showed high overall diagnostic values despite the different hemodynamic effects. It is concluded that stress echocardiography is extremely useful as a screening test for angina pectoris.

Although left ventricular (LV) inflow and pulmonary venous (PV) flow variables estimated by transesophageal Doppler echocardiography (TEE) reflect pulmonary capillary wedge pressure (PCWP), they are also affected by changes in cardiac function. The purpose of the present study was to detect the most appropriate variable for the estimation of PCWP by TEE in patients (pts) with ischemic heart disease. Several variables of LV inflow and left upper PV flow were compared with PCWP in 36 pts (six with angina pectoris and 30 with old myocardial infarction). Early diastolic flow (E) and atrial contraction flow (A) were used as LV inflow while systolic forward flow (X), diastolic forward flow (Y) and atrial contractile reversal flow (z) were used as PV flow. The peak velocity of each flow wave (Ep, Ap, Xp, Yp, and Zp) and the time-velocity integral (Ei, Ai, Xi, Yi, and Zi) were measured. The ratio of Ep to Ap (Ep/Ap), Ei to Ai (Ei/Ai), Xp to Yp (Xp/Yp), Xi to Yi (Xi/Yi), Zp to Ap (Zp/Ap), Zi to Ai (Zi/Ai) and the systolic fraction of PV forward flow were calculated. Among these variables, the Zi/Ai ratio was most strongly correlated with PCWP (R = 0.80). The Zi/Ai ratio may not be influenced by atrial function because the augmentation of atrial pump function increases Zi as well as Ai, and this may be one reason why the ratio correlated well with PCWP. Conclusion: The Zi/Ai ratio is a new useful variable for estimating PCWP by TEE.

Dobutamine stress echocardiography was used in the diagnosis of myocardial ischemia in patients with implanted VVI pacemakers. A 69-year-old woman received a pacemaker for Mobitz II type AV block in October 1992. She had suffered from chest pain during effort since January 1993 and underwent dobutamine stress echocardiography in April 1993. Although the electrocardiogram failed to identify ischemia because of the pacemaker rhythm, ischemia of the anterior wall was revealed as a worsening of the wall motion on the echocardiogram. The coronary angiogram showed 99% stenosis of the left descending artery. A direct coronary atherectomy was performed on the lesion. A 68-year-old man received a pacemaker for sick sinus syndrome in August 1993. He had suffered from chest oppression during effort since May 1992 and underwent dobutamine stress echocardiography in October 1993. Spontaneous rhythm appeared with dobutamine infusion, but the electrocardiogram could not demonstrate ischemia because of incomparability with the rhythm at rest. Echocardiography detected a new wall motion abnormality of the inferior wall caused by dobutamine. The coronary angiogram showed 90% stenosis of the right coronary artery. PTCA was performed on the lesion. Dobutamine stress echocardiography is useful for the diagnosis of myocardial ischemia in patients with implanted pacemakers.

The diagnostic usefulness of dipyridamole-stress two-dimensional echocardiography was assessed in 82 patients consisting of 27 patients with angina pectoris, 42 with myocardial infarction, and 13 control subjects. Two-dimensional echocardiographic monitoring was performed during dipyridamole infusion: 0.56 mg/kg for 4 minutes, then discontinuation for 4 minutes, followed by a final infusion of 0.28 mg/kg for 2 minutes. The cumulative dose was 0.84 mg/kg. Worsening or fixed wall motion abnormality with unaffected baseline indicated a positive finding. All patients underwent coronary angiography. The sensitivity and specificity of dipyridamole-stress two-dimensional echocardiography for diagnosis of significant coronary artery stenosis (≥ 75%) were 84% (58/69) and 92% (12/13), respectively. The sensitivity of this method for the branches of the coronary artery was 85% for the left anterior descending artery, 80% for the right coronary artery, and 75% for the left circumflex artery. The sensitivity for single-, double-, triple-vessel disease was 75%, 81% and 100%, respectively. The sensitivity and specificity of the dipyridamole electrocardiogram (ST depression more than 0.1 mV) were 33% (23/69) and 77% (10/13), respectively. The appearance of dipyridamole-stress induced wall motion abnormality was significantly earlier than those of chest pain and ST segment depression. Side effects were observed in 43% (35/82) of patients, but were only mild and transient. Dipyridamole-stress two-dimensional echocardiography is the best method for detecting coronary artery stenosis and predicting the localization of lesion sites.

A 39-year-old man was hospitalized because of a syncopal attack. There was a mitral ring calcification on the chest X ray films and 2-dimensional echocardiogram. The electrocardiogram showed ST-segment depression and negative T wave in the leads I, II, _aV_L, V_<5,6> and small Q wave in the leads V_<5,6>, and abnormal Q wave in the lead in V_4. These changes were found on the electrocardiogram taken 11 years before. A treadmill test showed a further ST-segment depression in V_<5,6> with mild chest pain. Stress thallium-201 myocardial scintigraphy showed perfusion defects at the apex and posterolateral wall, and redistribution at the posterolateral wall. Coronary angiography demonstrated 90% stenosis and a 7mm-sized aneurysm in the left circumflex artery. The proximal portion of the left anterior descending artery was completely occluded, and the occlusion was supplied with the huge collaterals from the right coronary artery. The right renal artery angiogram demonstrated multiple small aneurysms of 2 mm in size and numerous tortuous arteries. He gave no history of diabetes mellitus, hyperlipidemia and trauma. The syncopal attack was considered to be due to tachyarrhythmia because frequent ventricular premature beats and short run of ventricular tachycardia were recorded on admission. It may be deduced from the episode of high fever and eruption the patient had at the age of 4 years that the aneurysms of the coronary and the renal arteries of this case were probably caused by Kawasaki disease.

Dilated cardiomyopathy (DCM) is characterized by the dilation of the ventricles, the decrease of contractility and refractory heart failure which lead to a very poor prognosis. We report a case of DCM who showed refractory heart failure and underwent intensive treatment for about four years. The patient was a 37 year old woman who had a marked cardiomegaly, increased left ventricular dimension, the decrease of contractility, severe global hypokinesis and normal coronary arteries. Among new catecholamine analogues, denopamine and ibopamine showed a temporary improvement of cardiac failure, especially the latter was effective to increase urine volume. Vasodilators administered as a vasodilator therapy to reduce preload such as nitroglycerin were most effective, because right heart failure was predominant in this patient. Extra corporeal ultrafiltration method (ECUM) was useful for reducing volume overload.

医局論文番号436

Previous osteoporotic fracture, bone mineral density values, or bone turnover markers did not differ significantly between subjects with and without cardiovascular events in 15-year follow-up period of the Japanese Population-based Osteoporosis (JPOS) Cohort Study. In women aged younger than 65 year old at the 10-year follow-up survey, an annual change of ankle brachial index (ABI) during 5-year follow-up which is one of the index of atherosclerosis was significantly and positively correlated with an annual change of bone mineral density at the total hip and femoral neck during the same period independently of age, bone mineral density, and ABI values. Bone loss may be associated with advancing in atherosclerosis in women aged younger than 65 year old.

This study was conducted to investigate whether low bone mass predicts increased atherosclerosis. In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women aged 50 years or older in 2006 whose intima-media thickness of carotid bifurcation (BIF-IMT) was measured. Adjusted BIF-IMT values of subjects with spine T-score ? -1, between -2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19mm, 1.34mm, 1.57mm, respectively, in women with less than 10 years since menopause (YSM), 1.30mm, 1.32mm, 1.53mm, in women with YSM ?10 without a history of hypertension at baseline (both with p<0.05 for liner trend). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for the less than 10 YSM group) at baseline. In 2007, we set up the database with data of cardiovascular event. There was 21 cardiovascular events among 613 women aged 50 years or older followed in 2006. With multivariate analyses among premenopause, perimenopause, YSM<10, YSM ? 10, there was neither significance between lumbar bone status at baseline and cardiovascular event. Odds ratio of osteopenia for cardiovascular event was near significance of 36.76 (p=0.073) in YSM<10, after adjusting for age, weight, height, ratio of total cholesterol to HDL cholesterol, history of hypertension and diabetes mellitus, and smoking habits, at baseline. With similar analyses among 839 subjects including nonparticipation in 2006 followed by a questionnaire about information regarding cardiovascular event, there was neither significant relationship. Osteoporosis including prevalent vertebral fracture may predict carotid atherosclerosis in the next 10 years in postmenopausal women.