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Background: High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings., Methods and Results: This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population., Conclusions: Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.

Background: Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear., Methods and Results: HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study., Conclusions: In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.

Background: To predict mortality in patients with acute heart failure (AHF), we created and validated an internal clinical risk score, the KICKOFF score, which takes physical and social aspects, in addition to clinical aspects, into account. In this study, we validated the prediction model externally in a different geographic area., Methods and results: There were 2 prospective multicenter cohorts (1,117 patients in Osaka Prefecture [KICKOFF registry]; 737 patients in Kochi Prefecture [Kochi YOSACOI study]) that had complete datasets for calculation of the KICKOFF score, which was developed by machine learning incorporating physical and social factors. The outcome measure was all-cause death over a 2-year period. Patients were separated into 3 groups: low risk (scores 0-6), moderate risk (scores 7-11), and high risk (scores 12-19). Kaplan-Meier curves clearly showed the score's propensity to predict all-cause death, which rose independently in higher-risk groups (P<0.001) in both cohorts. After 2 years, the cumulative incidence of all-cause death was similar in the KICKOFF registry and Kochi YOSACOI study for the low-risk (4.4% vs. 5.3%, respectively), moderate-risk (25.3% vs. 22.3%, respectively), and high-risk (68.1% vs. 58.5%, respectively) groups., Conclusions: The unique prediction score may be used in different geographic areas in Japan. The score may help doctors estimate the risk of AHF mortality, and provide information for decisions regarding heart failure treatment.

Background: The clinical features of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) in Japan have not been fully elucidated., Methods and results: In 293 patients with HCM (median age at registration, 65 (57-72) years) in a prospective cardiomyopathy registration network in Kochi Prefecture (Kochi RYOMA study), HF events (HF death or hospitalization for HF) occurred in 35 patients (11.9%) (median age, 76 (69-80) years), including 11 HF deaths during a median follow-up of 6.1 years. The 5-year HF events rate was 9.6%. Atrial fibrillation, low percentage of fractional shortening, and high B-type natriuretic peptide level at registration were predictors of HF events. The combination of these 3 factors had a relatively high positive predictive value (55%) for HF events and none of them had a high negative predictive value (99%). There were 4 types of HF profile: left ventricular (LV) systolic dysfunction (40%), severe LV diastolic dysfunction (34%), LV outflow tract obstruction (LVOTO) (20%), and primary mitral regurgitation (MR) (6%). HF deaths occurred in patients with LV systolic dysfunction or LV diastolic dysfunction, but none of patients with LVOTO or primary MR due to additional invasive therapies., Conclusions: In a Japanese HCM cohort, HF was an important complication, requiring careful follow-up and appropriate treatment.

Background: Tafamidis has emerged as an effective treatment for patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA). The early experience of tafamidis treatment for Japanese patients with ATTRwt CA is reported here., Methods and results: Over the past 2 years, in 82 patients with ATTRwt CA (mean age of 81.7±6.0 years), tafamidis treatment was initiated for 38 patients. The remaining 44 patients were not administered tafamidis. The most frequent reason for non-administration of tafamidis was advanced heart failure and the second most reason was the patient's frailty. In patients who received tafamidis treatment, there was no discontinuation of tafamidis due to adverse events, the rate of cardiovascular-related hospitalizations per year was 0.19, and the 1-year survival rate was 92%. In the patients who continued tafamidis for 12-18 months, there was no significant deterioration from baseline for high-sensitivity cardiac troponin T level, plasma B-type natriuretic peptide level, left ventricular ejection fraction, inter-ventricular septum wall thickness, or value of left ventricular longitudinal strain., Conclusions: Tafamidis treatment was introduced for approximately half of the study patients with ATTRwt CA in real-world practice. Tafamidis is likely to be safe and may maintain the status of disease severity in the short-term in selected Japanese patients with ATTRwt CA. Further research is needed to determine appropriate patient selection for tafamidis treatment and efficacy of tafamidis in the long term.

Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant disorder mainly caused by mutations in sarcomere genes. Recently, a phenotype-based genetic test prediction score for patients with HCM was introduced by Mayo Clinic. The genotype score was derived on the basis of the predictive effect of 6 clinical markers, and the total score was shown to be correlated with the yield of genetic testing. However, it has not been determined whether this prediction model is useful in Japanese HCM patients., Methods and results: The utility of the Mayo Clinic HCM genotype predictor score in 209 Japanese unrelated patients with a clinical diagnosis of HCM who had undergone genetic testing for 6 sarcomere genes was assessed. Overall, 55 patients (26%) had pathogenic or likely pathogenic variants (60% being genotype-positive in familial cases). We divided the patients into 6 groups (groups with scores of from -1 to 5) according to the prediction score. The yields of genetic testing in the groups with scores of -1, 0, 1, 2, 3, 4, and 5 were 8%, 16%, 24%, 48%, 50%, 100%, and 89%, respectively, with an incremental increase in yield between each of the score subgroups (P<0.001)., Conclusions: The Mayo Clinic HCM genotype predictor score is useful for predicting a positive genetic test result in Japanese HCM Patients.

Background: Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomere genes. Regarding the clinical implications of genetic information, little is known about the lifelong clinical effect of sarcomere mutations in Japanese HCM patients., Methods and results: We studied 211 consecutive Japanese patients with HCM who had agreed to genetic testing between 2003 and 2013. Genetic analyses were performed by direct DNA sequencing in the 6 common sarcomere genes (MYH7,MYBPC3,TNNT2,TNNI3,TPM1,ACTC). Through variant filtering, 21 mutations were identified in 67 patients. After excluding 8 patients whose variants were determined as having uncertain significance, finally 203 patients (130 men, age at study entry: 61.8±14.1 years) were investigated for clinical presentation and course. At the time of study entry, patients with mutations were younger, had more frequent non-sustained ventricular tachycardia, had greater interventricular wall thickness, were more frequently in the dilated phase and less frequently had apical HCM. Through their lifetimes, a total of 98 HCM-related morbid events occurred in 72 patients. Survival analysis revealed that patients with sarcomere gene mutations experienced those morbid events significantly more frequently, and this tendency was more prominent for lethal arrhythmic events., Conclusions: In our HCM cohort, patients with sarcomere gene mutations had poorer lifelong outcome. Genetic information is considered important for better management of HCM.

Hypertrophic cardiomyopathy (HCM) is the most frequent hereditary cardiomyopathy, showing an autosomal-dominant f inheritance. A great deal of attention has been paid to genetics, left ventricular tract obstruction and the prediction and prevention of sudden cardiac death in HCM. Needless to say, these are very important, but we should recognize the heterogeneity in etiology, morphology, clinical course and management of this unique cardiomyopathy. Another important perspective is that HCM causes left ventricular remodeling over time and is a disease that requires lifelong management in the real world.

Background: There is limited information about the clinical profiles of patients with hypertrophic cardiomyopathy (HCM) and thromboembolic events in a community-based Japanese patient cohort., Methods and results: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture that comprised 9 hospitals, and finally 293 patients with HCM were followed. The mean age at registration was 63±14 years, and 197 patients (67%) were men. At registration, 86 patients (29%) had documented atrial fibrillation (AF). During a mean follow-up period of 6.1±3.2 years, thromboembolic events, including 3 embolic stroke deaths, occurred in 23 patients. The 5-year embolic event rate was 5.5%. During the follow-up period, an additional 31 patients (11%) had documentation of AF and finally a total of 117 patients (40%) developed AF. The 5-year embolic event rate in those 117 patients with AF was 12.3%. Of the 23 patients with embolic events, 12 had AF prior to the embolic complications and another 6 had documented AF after thromboembolism. AF was not detected in the remaining 5 patients. The CHADS 2 score did not correlate with the embolic outcome in HCM patients., Conclusions: In this community-based registry, thromboembolic events were not rare in patients with HCM. All patients with HCM in whom AF develops should be given anticoagulation therapy regardless of their CHADS 2 score.

Background: There have been few studies on the clinical course of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan., Methods and results: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally, 293 patients with HCM were followed. The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were male. HCM-related deaths occurred in 23 patients during a mean follow-up period of 6.1±3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a total of 77 cardiovascular events that were clinically severe occurred in 70 patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox proportional hazards model analysis showed that the presence of NYHA class III at registration was a significant predictor of HCM-related deaths and that the presence of atrial fibrillation, lower fractional shortening and presence of left ventricular outflow tract obstruction in addition to NYHA class III were significant predictors of cardiovascular events., Conclusions: In our unselected registry in an aged Japanese community, HCM mortality was favorable, but one-fifth of the patients commonly suffered from HCM-related adverse cardiovascular events during the 5-year follow-up period. Careful management of HCM patients is needed, particularly for those with the above-mentioned clinical determinants.

Background: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD. METHODS AND RESULTS: In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg·kg(-1)·day(-1)) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1α, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1β, and fibroblast growth factor 2 protein., Conclusions: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD.

Background: Hypertrophic cardiomyopathy (HCM), which is inherited as an autosomal dominant trait, is the most prevalent hereditary cardiac disease. Although there are several reports on the systematic screening of mutations in the disease-causing genes in European and American populations, only limited information is available for Asian populations, including Japanese., Methods and Results: Genetic screening of disease-associated mutations in 8 genes for sarcomeric proteins, MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TPM1, and ACTC, was performed by direct sequencing in 112 unrelated Japanese proband patients with familial HCM; 37 different mutations, including 13 novel ones in 5 genes, MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, were identified in 49 (43.8%) patients. Among them, 3 carried compound heterozygous mutations in MYBPC3 or TNNT2. The frequency of patients carrying the MYBPC3, MYH7, and TNNT2 mutations were 19.6%, 10.7%, and 8.9%, respectively, and the most frequently affected genes in the northeastern and southwestern parts of Japan were MYBPC3 and MYH7, respectively. Several mutations were found in multiple unrelated proband patients, for which the geographic distribution suggested founder effects of the mutations., Conclusions: This study demonstrated the frequency and distribution of mutations in a large cohort of familial HCM in Japan.

Background: Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear., Methods and Results: We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04 ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200 pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values., Conclusions: CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM., (All rights are reserved to the Japanese Circulation Society.)

Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. Although multiple gene mutations have recently been reported in Western countries, clinical implications of multiple mutations in Japanese subjects are not clear., Methods and Results: A comprehensive genetic analysis of 5 sarcomere genes (cardiac β-myosin heavy chain gene [MYH7], cardiac myosin-binding protein C gene [MYBPC3], cardiac troponin T gene [TNNT2], α-tropomyosin gene [TPM1] and cardiac troponin I gene [TNNI3]) was performed in 93 unrelated patients and 14 mutations were identified in 28 patients. Twenty-six patients had single heterozygosity (20 in MYBPC3, 4 in MYH7, 1 in TNNT2, 1 in TNNI3), whereas 2 proband patients with familial HCM had double heterozygosity: 1 with P106fs in MYBPC3 and R869C in MYH7 and 1 with R945fs in MYBPC3 and E1049D in MYH7. From the results of the family survey and the previous literature on HCM mutations, P106fs, R945fs and R869C seemed to be pathological mutations and E1049D might be a rare polymorphism. The proband patient with P106fs and R869C double mutation was diagnosed as having HCM at an earlier age (28 years of age) than her relatives with single mutation, and had greater wall thickness with left ventricular outflow obstruction., Conclusions: One double mutation was identified in a Japanese cohort of HCM patients. Further studies are needed to clarify the clinical significance of multiple mutations including phenotypic severity.

Background: The impact of matrix metalloproteinase (MMP) on left ventricular (LV) remodeling and heart failure events is unresolved in patients with hypertrophic cardiomyopathy (HCM)., Methods and Results: Plasma levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and clinical findings and heart failure events were evaluated in 41 HCM patients, including 8 with LV systolic impairment. Plasma B-type natriuretic peptide (BNP) levels were also measured. MMP-2 levels in patients with severe symptoms were higher than that in those with no or mild symptoms. The levels of MMP-2 and TIMP-1 were positively related to LV end-systolic and left atrial dimensions, and inversely related to LV ejection fraction. MMP-2 levels were positively related to BNP levels (r=0.52, P=0.0009). However, MMP-9 levels were not related to echocardiographic parameters and plasma BNP levels. Six patients had complicated heart failure events during the follow-up period of 3.2+/-0.7 years. Patients with high plasma MMP-2 levels (>1,170 ng/ml) revealed a poorer prognosis than those with low MMP-2 levels., Conclusions: Elevated levels of MMP-2 were related to LV remodeling and poor prognosis in patients with HCM. These results suggest that regulation of the extracellular collagen matrix might be one of the therapeutic targets in patients with HCM.

Background: Hypertrophic cardiomyopathy (HCM) with an apical phenotype, in which hypertrophy of the myocardium predominantly involves the apex of the left ventricle, is not uncommon in Japan, but its morphologic variations are not well recognized. The aim of this study was to investigate if these variations have different clinical characteristics although they are still confused to be the same., Methods and Results: Patients with the apical phenotype were divided into 2 groups, the "pure-apical" form and the "distal-dominant" form, and their clinical profiles were compared. From the study cohort of 264 patients with HCM, 80 (30%) were classified as having the apical phenotype: 51 with the pure-apical form and 29 with the distal-dominant form. The age at diagnosis was approximately 60 years, and in both groups the majority were male. The distal-dominant group had a significantly larger left atrial diameter (43 vs 39 mm) and higher ratio of proven familial HCM (28 vs 6%), and were more symptomatic (New York Heart Association >or=3) at presentation (17 vs 0%). The event-free rate of cardiovascular events in patients with the distal-dominant form was significantly worse (log-rank P=0.012) than that in patients with the pure-apical form (follow-up period: asymptotically approximately 5 years)., Conclusions: The 2 phenotypes of apical HCM should be recognized and distinguished clinically.

Background: There have been few studies of the clinical features of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan., Methods and Results: Cardiomyopathy registration was established in Kochi Prefecture and named the Kochi RYOMA (registry of myocardial diseases) study, consisting of 9 hospitals that registered 261 patients with a diagnosis of HCM. At registration, 74 patients (28%) had documented paroxysmal or chronic atrial fibrillation (AF). Although most patients (93%) were in New York Heart Association (NYHA) class I or II, 17 of the 18 patients in NYHA III had AF; 37 of the 74 patients with AF suffered from morbid events (embolism and/or heart failure (HF) admission), and 15 of 19 patients with embolic events had AF prior to or at the time of embolism. Of the 29 patients who had a history of HF admission, 8 had left ventricular systolic dysfunction, and the other 21 patients were hospitalized because of diastolic HF. AF occurred prior to HF in 20 of those 21 patients. Furthermore, 19 of those 20 patients with AF and diastolic HF were hospitalized within 1 year after detection of AF., Conclusions: In an unselected regional registry, AF was the major determinant of clinical deteriorations in patients with HCM.

Background: The purpose of the present study was to assess the clinical long-term course of hypertrophic cardiomyopathy (HCM) in a rural Japanese cohort., Methods and Results: A total of 137 consecutive HCM patients (mean age at diagnosis: 52+/-13 years) were enrolled. During a follow-up period of 11.4+/-5.7 years, 28 patients died of HCM-related causes. Eleven patients died suddenly, 10 died of progressive heart failure, 6 died of stroke associated with atrial fibrillation and 1 died of a postoperative complication of alcohol septal ablation. For the overall study group, 5-, 10- and 15-year cumulative survival rates were 91%, 88% and 79%, respectively. Although sudden death was the predominant cause of HCM-related death during the follow-up period of <10 years, heart failure death increased after follow-up period of >10 years. Fifteen (13%) of 114 patients who had follow-up echocardiography became ;end-stage' HCM and 8 patients died of severe and refractory heart failure. They already showed minimally dilated left ventricular (LV) dimension and lower LV fractional shortening at initial evaluation., Conclusions: Although HCM patients in a Japanese rural community showed relatively benign clinical course (the same as cohorts in the developed world), heart failure death because of LV remodeling became equally important to sudden death when they were followed for more than 10 years.

Background: Several morphologic distinctions between elderly and young patients with hypertrophic cardiomyopathy (HCM) have been reported. In particular, a crescent-shaped left ventricular (LV) cavity with reversed septal curvature, which is often seen in young patients, is rare in elderly patients. However, those studies were carried out before gene testing became available and heterogeneous causes or age-related changes may have been included. The purpose of this study was to determine the morphologic characteristics of elderly patients with HCM definitely caused by a mutation in the cardiac myosin-binding protein C (MyBPC)., Methods and Results: Twenty-seven patients with HCM caused by MyBPC gene abnormality were evaluated. Patients were divided into an elderly group (> or = 65 years of age, n = 8) and a young group (< 65 years of age, n = 19). LV hypertrophy was milder in the elderly than in the young for maximum LV wall thickness (18 +/- 5 mm vs 24 +/- 6 mm, p = 0.008) and Wigle score (5.7 +/- 1.5 vs 7.6 +/- 1.6, p < 0.005). However, an abnormal crescent-shaped LV was similarly prominent in both groups (75% in the elderly vs 95% in the young, p = NS). None of the elderly patients showed a proximal septal bulge., Conclusions: An abnormal crescent-shaped LV cavity was frequently present in the elderly as in the young when there are MyBPC mutations. It is possible that this morphologic feature could become useful for determining the etiology of HCM in elderly patients.

Background: Because of their favorable prognostic effects, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and beta blockers have become background therapy in dilated cardiomyopathy (DCM). However, there are few reports concerning the long-term prognosis of Japanese patients with DCM in relation to these treatments., Methods and Results: One hundred and fifty patients with DCM were divided into 2 groups: group A (n=46) (diagnosis: 1982-1989) and group B (n=104) (diagnosis: 1990-2002). During follow-up period of 6.9+/-4.8 years, 62 patients died and 1 patient had a heart transplant. The survival rate at 5 and 10 years was 60.9% and 34.8%, respectively, in group A patients, and 80.9% and 65.3%, respectively, in group B patients (p=0.0079). In group A patients, ACEI/ARB or beta blockers were less frequently used (p<0.0001), whereas antiarrhythmics (class Ia or Ib) were more often used (p<0.0001). The patients treated with ACEI/ARB and beta blockers showed a better survival rate than those without (p<0.0001). The patients with antiarrhythmics showed a worse survival rate than those without (p<0.0001)., Conclusion: The prognosis of Japanese patients with DCM has significantly improved over the past 20 years. This improvement may be explained partly through the increased use of ACEI/ARB and beta blockers and a declining use of antiarrhythmics.

Background: Hypertrophic cardiomyopathy (HCM) might exhibit not only diastolic, but also latent systolic dysfunction. Therefore combined assessment of both systolic and diastolic function using myocardial performance index (Tei index) can be useful in HCM. Plasma brain natriuretic peptide (BNP) level is reported to be elevated in HCM, but the mechanism of BNP elevation in HCM remains to be established., Methods and Results: The value of Tei index in 45 HCM patients was compared with that of 20 normal control subjects. The HCM patients showed a higher value of Tei index (0.55+/-0.12 vs 0.36+/-0.08, p < 0.0001) and longer isovolumic relaxation and contraction times than control subjects. The plasma BNP level correlated with Tei index in non-obstructive HCM (n = 35, r = 0.61, p < 0.0001), although the correlation was mild when overall HCM patients were included (r = 0.34, p = 0.02). The correlation was still significant after adjusting for age, or the extent and severity of left ventricular hypertrophy. Multiple stepwise regression analysis identified mitral E/A ratio (r = 0.49, F = 13.1) and Tei index (r = 0.37, F = 7.6) as independent predictors of higher plasma BNP level in non-obstructive HCM., Conclusions: Myocardial performance index was abnormal in HCM, reflecting both systolic and diastolic dysfunction in this disorder. Plasma BNP level correlated with functional assessment by Tei index in non-obstructive HCM.

The long-term prognosis of patients with mildly dilated cardiomyopathy (MDCM) was investigated in 21 patients. MDCM was defined as left ventricular ejection fraction < or = 40% and left ventricular end-diastolic volume < or = 120 ml/m2 by left ventriculography. During a follow-up period of 6.8+/-3.7 years, there were 9 cardiac events (5 heart failure deaths, 2 sudden deaths, and 2 re-hospitalizations for heart failure). Only in the patients without cardiac events was there a significant decrease in left ventricular size (end-diastolic dimension decreased from 58+/-6 mm to 50+/-8 mm, p<0.001) and an improvement in systolic function (fractional shortening increased from 17+/-5% to 26+/-11%, p=0.007). However, left atrial dilation was observed in the patients with an event (from 39+/-5 mm to 43+/-5 mm, p=0.02). Based on proportional hazard analysis, left ventricular end-diastolic pressure and mean pulmonary artery pressure at diagnosis and left atrial dimension at the time of follow-up were significant predictors of poor outcome. A subset of patients with MDCM has impaired hemodynamics at diagnosis, left atrial dilation at follow-up and a poor prognosis, and must be followed carefully even if the left ventricular dilatation is mild.

To evaluate the functional recovery after coronary bypass surgery in patients with severe left ventricular (LV) dysfunction (ejection fraction (EF) < or = 35%), 100 consecutive patients with viable myocardium in the territory supplied by the left anterior descending artery (LAD) underwent coronary bypass grafting. In addition, cardiac catheterization and single-photon emission computed tomography (SPECT) perfusion imaging with thallium-201 were repeated 1-year postoperatively. Although 12 patients with severe LV dysfunction were preoperatively in a worse New York Heart Association functional class (3.1+/-0.7 vs 2.4+/-0.8; p<0.01), had a higher incidence of heart failure (10/12 vs 14/88; p<0.001) and had a worse LVEF (29+/-5 vs 61+/-14%; p<0.001) compared with 88 patients without severe LV dysfunction, the operative mortality was similar in the 2 groups (1/12 vs 2/88; p=NS). The postoperative NYHA functional class in the patients with severe LV dysfunction was similar to that in the patients without such dysfunction (1.6+/-0.7 vs 1.3+/-0.6; p=NS). In addition, the 1-year postoperative study revealed a significant improvement in the thallium defect score in both the LAD territory (1.7+/-1.2 to 0.7+/-1.0, p=0.01) and all the territories (5.2+/-2.2 to 3.2+/-1.9, p=0.002) in patients with severe LV dysfunction, whereas no improvement in defect score was found in either of these territories in those without severe LV dysfunction (LAD: 0.6+/-1.4 to 0.4+/-1.2, p=NS; All: 1.9+/-2.2 to 1.8+/-2.0, p=NS). Furthermore, a marked 1-year postoperative improvement (15-24%; 95% confidence interval) in LVEF (29+/-5 to 48+/-10%, p<0.001) was demonstrated in patients with severe LV dysfunction, but not in those without such dysfunction (60+/-13 to 61+/-11%, p=NS). These results indicate that myocardial viability in the LAD territory, as demonstrated by thallium-201 SPECT perfusion imaging, predicts a significant improvement in functional class and LVEF of at least 10% or more after coronary artery bypass grafting in patients with severe LV dysfunction.

Although the aVL lead in exercise electrocardiography is reported to be helpful in identifying a significant narrowing of the left anterior descending coronary artery (LAD), its role in exercise testing has not been fully evaluated. Accordingly, 821 patients who underwent both standard exercise testing and coronary angiography were evaluated. In patients with aVL lead ST elevation, the incidence of a significant narrowing of the LAD (124/165 vs 348/656; p<0.001) was higher than in those without. Multiple logistic regression analysis revealed that the 2 most important variables that correlated with aVL lead ST elevation were a greater number of leads with ST depression in the inferior leads and a smaller amplitude of R wave in the aVL lead. In contrast, variables correlating with aVL lead ST depression in the majority of cases were a greater number of leads with ST depression in all leads and the presence of inferior lead ST elevation. The results of this study indicate that although aVL lead ST elevation could be a marker for LAD narrowing, more important factors such as inferior lead ST-segment depression and the R-wave amplitude of the aVL lead should be taken into consideration. In contrast, ST depression in the aVL lead mostly represents exercise-induced myocardial ischemia of greater extent and severity.

To detect a significant narrowing of the left anterior descending artery in patients with inferior/posterior myocardial infarction, 200 patients underwent standard exercise testing. Age, gender, and grade of stenosis of the left anterior descending artery were similar in 138 patients with inferior myocardial infarction and 62 with posterior myocardial infarction. In patients with left anterior descending artery stenosis, there were more lateral leads with ST-segment depression (1.8+/-1.0 vs 1.1+/-1.1; p<0.01) and fewer anterior leads with ST-segment depression (2.1+/-1.4 vs 2.9+/-1.4; p=0.02) in those with inferior myocardial infarction than in those with posterior myocardial infarction. Applying the criterion of exercise-induced ST-segment depression > or = 0.1 mV, sensitivities and specificities in detecting left anterior descending artery stenosis were 98% and 21% respectively in inferior myocardial infarction and 94% and 26% respectively in posterior myocardial infarction. In contrast, discriminant analysis revealed sensitivities and specificities of 77% and 91% respectively in inferior myocardial infarction and 71% and 81% respectively in posterior myocardial infarction using the variables related to severity of inducible ischemia and lateral and anterior lead ST-segment depression. These results indicate that a multivariate approach underscoring the site of myocardial infarction can help in identifying stenosis of the left anterior descending artery in patients with inferior/posterior myocardial infarction.