Effects of renin-angiotensin system inhibitor and beta-blocker use on mortality in older patients with heart failure with reduced ejection fraction in Japan.

Introduction: Guideline-directed medical therapy with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved the survival of patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, it is unclear whether RAS inhibitors and beta-blockers can be administered to older patients with HF. Therefore, this study aimed to investigate the effects of beta-blockers and RAS inhibitors on the prognosis of older patients with HFrEF. Methods: Demographic, clinical, and pharmacological data from 1,061 patients with acute decompensated HF, enrolled in the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI study), were analyzed to assess their impact on mortality. Additionally, a machine learning approach was applied to complement the conventional statistical model for analysis. Patients with HFrEF (n = 314) were divided into the all-cause mortality within 2 years group (n = 80) and the survivor group (n = 234). Results: Overall, 41.1% (129/314) of the patients were aged ≥80, and 25.5% (80/314) experienced all-cause mortality within 2 years. Furthermore, 57.6% (181/314) and 79.0% (248/314) were prescribed RAS inhibitors and beta-blockers, respectively. Our analysis showed that RAS inhibitor use was associated with reduced all-cause mortality and cardiac death in patients with HFrEF of all ages (P < 0.001), and beta-blocker use had an interaction with age. Machine learning revealed that the use of beta-blockers altered the risk of mortality, with a threshold of approximately 80 years of age. Beta-blocker use was associated with lower all-cause mortality and cardiac death in patients with HFrEF aged <80 years (P < 0.001) but not in those aged ≥80 years (P = 0.319 and P = 0.246, respectively). These results suggest that beta blockers may differ in their all-cause mortality benefits according to age. Conclusions: RAS inhibitors prevented all-cause mortality and cardiac death at all ages, whereas beta-blockers had different effects depending on the patient's age. This study suggested that the choice of beta-blockers and RAS inhibitors is more important in older patients with HFrEF than in younger patients with the same condition.

Prognostic impact of frailty based on a comprehensive frailty assessment in patients with heart failure.

AIMS: This study aimed to evaluate the impact of frailty and living function domains based on the Kihon Checklist (KCL), a questionnaire for a comprehensive frailty assessment, on prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: The Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study was a prospective multicentre cohort study enrolling 1061 patients hospitalized for AHF from May 2017 to December 2019 in Japan. We divided patients into three groups according to the severity of frailty using the KCL and compared clinical outcomes after discharge. The primary endpoint was all-cause death, and the secondary outcomes were cardiovascular death, heart failure (HF) rehospitalization, and the composite event of cardiovascular death and HF rehospitalization. Of 936 patients (median age, 81 years; 48.9% women) who could be assessed for frailty, we identified frailty in 501 patients (53.5%), prefrailty in 290 patients (31.0%), and non-frailty in 145 patients (15.5%). Compared with prefrail and non-frail patients, frail patients were older (83 vs. 79 and 72 years, P < 0.001), were more likely to be women (53.9% vs. 43.1% and 43.4%, P = 0.005), and were more likely to have a history of previous HF hospitalization (35.4% vs. 25.3% and 19.6%, P < 0.001) and multimorbidity (90.8% vs. 81.0% and 73.8%, P < 0.001). Frail patients had a lower rate of discharge to home (79.7% vs. 94.8% and 96.5%, P < 0.001). During the 2 year follow-up period, frail patients had a higher incidence rate of all-cause death, cardiovascular death, and HF rehospitalization (log-rank P < 0.001, P < 0.001, and P = 0.003, respectively). After adjusting for other prognostic factors, multivariate analysis showed that frailty was associated with all-cause death [adjusted hazard ratio (HR): 2.917, 95% confidence interval (CI): 1.326-6.417, P = 0.008] and cardiovascular death (adjusted HR: 7.026, 95% CI: 1.700-29.030, P = 0.007). Among all domains of the KCL, the cognitive function domain was associated with a higher risk of all-cause death (P = 0.004) and cardiovascular death (P < 0.001). The depression domain remained associated with a higher risk of HF rehospitalization (P = 0.045). The risk for all-cause death increased with an increase in total KCL score (adjusted HR: 1.819, 95% CI: 1.300-2.547, P < 0.001). CONCLUSIONS: The KCL is a useful tool for risk stratification of adverse outcomes in patients with AHF. Functional declines in psycho-emotional domains including cognitive function and depressed mood contribute to adverse outcomes.

Associations between electrocardiographic findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy.

BACKGROUND: The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood. METHODS: One hundred forty patients (mean age: 62.9 ±â€¯15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis. RESULTS: In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV. CONCLUSIONS: In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment.

External Validation of the Japanese Clinical Score for Mortality Prediction in Patients With Acute Heart Failure.

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.

Frailty interferes with the guideline-directed medical therapy in heart failure patients with reduced ejection fraction.

AIMS: Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) is recommended in clinical guidelines, but elderly patients have not fully received GDMT in the clinical situation. The aim of this study was to determine the clinical characteristics of patients who have not received GDMT and the association between implementation of GDMT at discharge and physical frailty in patients with HFrEF who were hospitalized for acute decompensated heart failure (ADHF). METHODS AND RESULTS: This study was a cross-sectional study with a retrospective analysis of the Kochi YOSACOI study, a prospective multicentre observational study that enrolled 1061 patients hospitalized for ADHF from May 2017 to December 2019 in Japan. Of 339 patients (32.0%) with HFrEF, 268 patients who were assessed for physical frailty by the Japanese version of the Cardiovascular Health Study criteria were divided into two groups: those with GDMT (135 patients, 50.4%) and those without GDMT (133 patients, 49.6%). GDMT was defined as the prescription of a combination of renin-angiotensin system (RAS) inhibitors (angiotensin-converting inhibitors or angiotensin receptor blockers) and beta-blockers. The median age of patients with HFrEF was 76 years (interquartile range, 67-83 years). Patients without GDMT were older than patients with GDMT (73 years vs. 78 years, P < 0.001). Patients without GDMT tended to have more prior HF admission than did patients with GDMT (P = 0.004), and patients without GDMT had lower levels of estimated glomerular filtration rate (P < 0.001) than those in patients with GDMT. Physical frailty was observed in 54.1% of the patients without GDMT and in 38.5% of the patients with GDMT (P = 0.014). Patients without GDMT had a higher rate of cognitive impairment than that in patients with GDMT (P = 0.009). RAS inhibitors only, beta-blockers only, and both RAS inhibitors and beta-blockers were less frequently prescribed in patients with physical frailty than in patients with physical non-frailty (52.0% vs. 86.7%, P < 0.05; 70.1% vs. 100.0%, P < 0.05; 42.5% vs. 86.7%, P < 0.01, respectively). In logistic regression analysis, compared with physical non-frailty, physical frailty was significantly associated with no implementation of GDMT (odds ratio: 6.900, 95% confidence interval: 1.420-33.600; P = 0.017), independent of older age and severe renal dysfunction. CONCLUSIONS: The results of this study suggest that physical frailty is one of the factors that may withhold GDMT in patients with HFrEF.

Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort.

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.

Clinical characteristics and frailty status in heart failure with preserved vs. reduced ejection fraction.

AIMS: The aim of this study was to elucidate the clinical characteristics, including frailty status, of patients with heart failure with preserved ejection fraction (HFpEF) in comparison with those in patients with heart failure with reduced ejection fraction (HFrEF) in a super-aged region of Japan. METHODS AND RESULTS: Of the 1061 Japanese patients enrolled in the Kochi YOSACOI study, a multicentre registry, we divided 645 patients (median age of 81 years [interquartile range, 72-87 years]; women, 49.1%) into two groups, HFpEF patients (61.2%) and HFrEF patients (38.8%). Physical frailty was diagnosed on the basis of the Japanese version of Cardiovascular Health (J-CHS) Study criteria. Patients for whom left ventricular ejection fraction data were not available (n = 19), patients with heart failure with mildly reduced ejection fraction (n = 172), and patients who were not assessed by the J-CHS criteria (n = 225) were excluded. The median ages of the HFpEF and HFrEF patients were 84 and 76 years, respectively. The proportion of patients with HFpEF gradually increased with advance of age. The proportion of patients with three or more comorbidities was larger in HFpEF patients than in HFrEF patients (77.9% vs. 65.6%, P = 0.003). Handgrip strength was significantly lower in HFpEF patients than in HFrEF patients for both men (P < 0.001) and women (P = 0.041). Comfortable 5 m walking speed was significantly slower in HFpEF patients than in HFrEF patients (P < 0.001). The proportions of patients with physical frailty were 55.2% in HFpEF patients and 46.8% in HFrEF patients, and the proportion was significantly higher in HFpEF patients (P = 0.043). In multivariate analysis, physical frailty was associated with advanced age [odds ratio (OR), 1.030; 95% confidence interval (CI), 1.010-1.050; P = 0.023] and low albumin level (OR, 0.334; 95% CI, 0.192-0.582; P < 0.001) in HFpEF patients, and physical frailty was associated with women (OR, 2.150; 95% CI, 1.030-4.500; P = 0.042) and anaemia (OR, 2.840; 95% CI, 1.300-6.230; P = 0.003) in HFrEF patients. CONCLUSIONS: In a super-aged population of HF patients in Japan, HFpEF patients are more likely to be frail/have a high frailty status compared with HFrEF patients. The results suggested that physical frailty is associated with extracardiac factors in both HFpEF patients and HFrEF patients.

Assisted Living and Medication Adherence in Super-aged Patients With Heart Failure in the Japanese Population.

ABSTRACT: Poor adherence to medication in patients with heart failure (HF) is associated with poor clinical outcomes. Although social support has been reported to improve medication adherence in patients with HF, the detailed underlying mechanism of this association is unclear. This study investigated appropriate social support types to ensure medication adherence, as well as patient characteristics that benefit from such social support in patients with HF. This was a retrospective observational study investigating the association of social support with medication adherence in 824 patients with HF who were registered in a prospective multicenter database. First, we analyzed the association between social support types and poor medication adherence leading to hospitalization. An interaction analysis was performed to detect patients' characteristics that benefited most from social support in terms of medical adherence. Fifty patients (6.1%) were hospitalized for poor adherence to medications. Multivariable analysis revealed that not receiving assisted living, which was defined as having supporting individuals at least once a week, was independently associated with poor medication adherence-related hospitalization. An interaction analysis revealed that patients with dementia benefited from assisted living significantly, whereas male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence in patients with HF and was particularly effective in patients with dementia. Performed in a super-aging region in Japan, this study may also suggest the relevance of social support in preventing HF exacerbation in other developed countries that will experience an aging society in the near future.

Wild-Type Transthyretin Amyloidosis in Female Patients　- Consideration of Sex Differences.

Background: With recent advances in non-invasive diagnostic tools, some studies indicate that wild-type transthyretin amyloidosis (ATTRwt) may be more common in females than previously reported. However, the clinical characteristics of female ATTRwt patients have not been determined. Methods and Results: Of the 78 consecutive patients with ATTRwt in our cohort, 14 (17.9 %) were female. Compared with male patients, female ATTRwt patients had smaller left ventricular (LV) wall thicknesses (ventricular septum thickness 12.9 vs. 14.2 mm [P=0.081]; posterior wall thickness 12.7 vs. 13.6 mm [P=0.035]) and a higher LV ejection fraction (EF; mean [±SD] 58.4±8.9% vs. 48.9±11.8%; P=0.006). However, the severity of heart failure (HF), as assessed by HF stage, New York Heart Association functional class and B-type natriuretic peptide concentrations, did not differ between female and male patients. Moreover, LV mass index and relative wall thickness were increased and the stroke volume index was reduced in both female and male patients. In organ biopsies, female patients had a higher sensitivity to transthyretin deposition from abdominal fat than male patients (positive abdominal fat biopsy 80.0 % vs. 26.5%; P=0.016). Conclusions: This study suggests that a relatively large proportion of elderly females have ATTRwt. Female ATTRwt patients had HF symptoms even at the stage of mild LV hypertrophy and preserved EF. Abdominal fat biopsy may be useful to diagnose ATTRwt, especially in female patients with HF.

Frailty in patients with acute decompensated heart failure in a super-aged regional Japanese cohort.

AIMS: The aim of this study was to investigate clinical characteristics of frail patients based on a comprehensive frailty assessment in patients hospitalized for acute decompensated heart failure (HF) (ADHF) in super-aged regional Japanese cohort. METHODS AND RESULTS: We established the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study, which was a prospective multicentre community-based cohort study in six participating hospitals in Kochi Prefecture, Japan. We enrolled 1061 patients (median age, 81 years; 50.0% men) hospitalized for ADHF between June 2017 and December 2019 in this registry. Patients were classified into the three groups by the severity of frailty using the Kihon Checklist: we identified frailty in 510 patients (53.7%), prefrailty in 293 patients (30.9%), and non-frailty in 146 patients (15.4%). Compared with prefrail and non-frail patients, frail patients were older (84 years interquartile range [IQR, 77-88] vs. 79 years [IQR, 69-86] and 72 years [IQR 65-81], P < 0.001) and more often had prior HF hospitalization (29.6% vs. 21.8% and 16.4%, P < 0.05), chronic kidney disease (81.6% vs. 71.7% and 61.0%, P < 0.01), anaemia (75.3% vs. 61.4% and 50.0%, P < 0.001), cerebrovascular accident (19.0% vs. 9.9% and 4.1%, P < 0.01). The proportion of patients with three or more comorbidities was larger in the frailty group than in the other groups (78.0% vs. 67.2% and 63.0%, P < 0.01). The frequency of functional decline in all domains increased with frailty status. Approximately 70% of frail patients were identified as functional decline in physical function and socialization domains. Fifty to sixty per cent of frail patients had functional decline in instrumental activities of daily living, cognitive function, and depression domains. The percentage of worsening walking ability during hospitalization was increasing with the frailty status (frailty, 27.5%; prefrailty, 21.8%; non-frailty, 8.9%). In multivariate logistic regression analysis, frailty was associated with age [odds ratio (OR) 1.031, 95% confidence interval (CI) 1.011-1.052, P = 0.003], prior HF hospitalization (OR 1.789, 95% CI 1.165-2.764, P = 0.008), brain natriuretic peptide level at discharge (OR 1.001, 95% CI 1.000-1.001, P = 0.020) and prior cerebrovascular accident (OR 2.549, 95% CI 1.484-4.501, P < 0.001). CONCLUSIONS: More than half of patients with ADHF were frail and had functional decline across multiple domains, not only physical function domain. The Kihon Checklist provided useful and valuable information for easily identifying frail patients and comprehensive management of HF.

First principles density functional+U pseudopotential study on the electronic structure of layered perovskite LaSr3Fe3O10.

The electronic, magnetic and crystal structures of layered perovskite oxide LaSr3Fe3O10 (LSFO) in the Ruddlesden-Popper structure were studied from first principles using the density functional theory (DFT)+U pseudopotential (PP) method and a self-consistent constrained DFT technique (Hamada and Ohno 2019 J. Phys.: Condens. Matter 31 065501). Using this technique, the magnetic structure of LSFO was determined to be antiferromagnetic and an effective Hubbard on-site interaction parameter for Fe 3d electrons, U eff(Fe3d ) = 6.08 eV was identified for LSFO. The DFT+U PP calculations of LSFO models using this U eff(Fe3d ) value reproduced the experimentally observed metallic characteristics and crystal structure of LSFO, demonstrating the correct determination of the U eff(Fe3d ) value of the large and complex LSFO material. The first-principles DFT+U calculation of large and complex strongly-correlated systems was enabled using the self-consistent constrained DFT technique.

A new constraint DFT technique for self-consistent determination of U values.

A new constraint density functional (DFT) technique workable in combination with the projector augmented wave (PAW) and pseudoptential (PP) methods was developed. This technique calculates the effective on-site-interaction parameter, U eff, of correlated electrons of materials, self-consistently, by using the DFT + U method. The U eff determined by this technique has a clear physical meaning in that it determines the electronic structures of strongly correlated electronic systems (SCESs) and vice versa. The technique was used to determine the U eff of correlated electrons of neodymium sesquioxide (Nd2O3) and iron oxide (FeO), and it was shown to be effective for this purpose. It enables first principles DFT + U PAW and PP calculations of SCESs free from any empirical parameters.

Predictive factors of rehospitalization for worsening heart failure and cardiac death within 1 year in octogenarians hospitalized for heart failure.

AIM: To investigate the predictive factors of cardiac events including rehospitalization for worsening heart failure (HF) and cardiac death within 1 year after hospital discharge in octogenarians hospitalized for HF. METHODS: We retrospectively analyzed in detail clinical data for patients aged >80 years who were admitted to Kochi University, Kochi, Japan, for acute decompensated HF in order to identify predictive factors for cardiac events within 1 year. RESULTS: A total of 67 patients (mean age of 85 ± 4 years, 39 men) were included, and 28 patients (41.8%) had cardiac events. The patients with cardiac events were significantly older, had a lower prescription rate of beta-blockers at discharge and had a lower rate of arrhythmia as an exacerbating factor of HF than patients without cardiac events. When nutritional status was assessed by the controlling nutritional status (CONUT) score, patients in the cardiac events group had significant malnutrition (CONUT ≥5). In addition, Kaplan-Meier analysis showed that patients with CONUT ≥5 had a higher incidence of cardiac events than did those with a CONUT <5 (log-rank, P < 0.038). In logistic analysis, the independent determinants of the cardiac events within 1 year were malnutrition at moderate or severe levels by the CONUT score and no beta-blocker medication. CONCLUSIONS: In very elderly patients hospitalized for HF, malnutrition and no beta-blocker medication were predictors of rehospitalization for worsening HF or cardiac death within 1 year. These factors could be meaningful targets for improving the management of octogenarians with HF. Geriatr Gerontol Int 2018; 18: 101-107.

Impact of Statins Therapy for Ischemic Heart Disease Patients with Low-Density Lipoprotein Cholesterol Levels Less Than 100 mg/dL.

BACKGROUND: The objective of this study was to determine whether the use of statins prevents the progression of ischemic heart disease (IHD) in patients with low levels of low-density lipoprotein cholesterol (LDL-C). METHODS: We reviewed data obtained from IHD patients who underwent first percutaneous coronary intervention (PCI). Patients underwent follow-up coronary angiography (re-CAG) after PCI. However, only patients with LDL-C levels less than 100 mg/dL at PCI were included in this study. Ultimately, 92 patients were enrolled. All patients were divided into two groups: 1) patients who were treated with statins (n = 69), and 2) patients who were not treated with statins (n = 23). RESULTS: The two groups had similar LDL-C levels at PCI. At re-CAG, the ratio of patients who underwent PCI for de novo lesion in the statin group was lower than that in the non-statin group (12% vs. 48%) (p < 0.001). In multiple regression analysis, statin usage and LDL-C level at PCI were independent predictors of the ratio of patients undergoing PCI for de novo lesion. CONCLUSIONS: Statins therapy for patients whose LDL-C levels are less than 100 mg/dL has a beneficial effect on secondary prevention of IHD.

Clinical features of the dilated phase of hypertrophic cardiomyopathy in comparison with those of dilated cardiomyopathy.

BACKGROUND: Although the dilated phase of hypertrophic cardiomyopathy (D-HCM) characterized by left ventricular (LV) systolic dysfunction and cavity dilatation has been reported to be a poor prognosis, this is now in contrast to the improved prognosis of dilated cardiomyopathy (DCM) in the era of advancements in heart failure management. There has been no investigation of the clinical features of D-HCM compared with those of DCM from the point of management of systolic dysfunction. HYPOTHESIS: The aim of this study was to investigate the clinical features of D-HCM in comparison with those of DCM in a single institute. METHODS: We studied 20 consecutive patients with D-HCM (global ejection fraction < 50%) and 115 consecutive patients with DCM. RESULTS: At diagnosis of D-HCM, 8 (40%) of the D-HCM patients already experienced dyspnea (New York Heart Association [NYHA] class >or= III). Left atrial diameter was larger and prevalence of atrial fibrillation was higher in the D-HCM group, although LV size was larger and LV ejection fraction was lower in the DCM group. During the follow-up period (4.0 years), 11 (55%) of the patients with D-HCM died. The 5-year survival rate from all-cause mortality including cardiac transplantation was 45.6% in patients with D-HCM vs 81.6% in patients with DCM (log-rank P = .0001). CONCLUSIONS: Patients with D-HCM were more symptomatic at diagnosis, although LV dilatation and impaired fractional shortening seemed more severe in patients with DCM. The prognosis for D-HCM patients was worse than that for patients with DCM despite similar or even more intensive treatment for heart failure.

A frameshift deletion mutation in the cardiac myosin-binding protein C gene associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy.

OBJECTIVES: A few studies reported that some mutations in the cardiac myosin-binding protein C (MyBPC) gene were associated with dilated phase of hypertrophic cardiomyopathy (D-HCM) resembling dilated cardiomyopathy (DCM). We studied 5 unrelated cardiomyopathy probands caused by an identical mutation in the MyBPC gene. The results of clinical and genetic investigations in these patients are presented in this paper. METHODS: We analyzed MyBPC gene in DCM patients as well as patients with HCM. RESULTS: An R945fs/105 mutation, 2-base deletion at nucleotides 18,535 and 18,536, was identified in 4 of the 176 HCM probands and in 1 of the 54 DCM probands. Genetic analysis in relatives of those probands revealed another one member with this mutation. A total of 6 subjects had R945fs/105 mutation. The mean age of these six patients at diagnosis was 61 years. At initial evaluation, three of them were diagnosed as having HCM with normal left ventricular (LV) systolic function. The other two patients already had D-HCM. The remaining one patient was diagnosed as having DCM because of reduced LV systolic function (ejection fraction=31%) without increased LV wall thickness. During follow-up (7.6 years), all three patients with impaired LV systolic function were admitted for treatment of heart failure and/or sustained ventricular tachycardia. Finally, one patient with the diagnosis of D-HCM died of heart failure. CONCLUSIONS: The patients with this mutation may develop LV systolic dysfunction and suffer from cardiovascular events through mid-life and beyond.

A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy.

BACKGROUND: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) have been reported to be associated with delayed expression of hypertrophic cardiomyopathy (HCM) and a relatively good prognosis. PURPOSE: The aim of this study was to evaluate clinical manifestations in patients with familial HCM caused by a novel nonsense mutation, S297X, in MYBPC3. METHODS: We analyzed the sarcomere protein genes in 93 probands with HCM. RESULTS: The nonsense mutation S297X in MYBPC3 was present in nine subjects from two unrelated families. Eight of those nine subjects with this mutation were found to be phenotype-positive and the remaining individual was not affected phenotypically. The age range at diagnosis was 9-75 years. There was no family history of sudden death in either family. At presentation, there were various left ventricular hypertrophy (LVH) patterns, including Maron type III hypertrophy from the LV base to apex, hypertrophy confined to the anterolateral wall at the basal LV wall. Two patients showed a significant LV outflow tract gradient and one patient showed intra-right-ventricular obstruction. During follow-up, one patient was repeatedly hospitalized for the treatment of heart failure after development of paroxysmal atrial fibrillation at the age of 86 years and the remaining eight subjects were in relatively stable condition and did not require hospitalization for the treatment of HCM-related events. CONCLUSION: The novel mutation S297X in MYBPC3 causes HCM in a broad range of ages and heterogeneous clinical manifestations, though the clinical course in patients with this mutation seems to be benign.

Improvement in prognosis of dilated cardiomyopathy in the elderly over the past 20 years.

BACKGROUND AND PURPOSE: Although dilated cardiomyopathy (DCM) had a poor prognosis in the past, recent studies have shown better survival. However, little is known about the improvement of prognosis in the elderly. This study sought to clarify the changes in prognosis in elderly patients with DCM over the past 20 years. METHODS AND SUBJECTS: We studied 54 consecutive patients with DCM (38 men and 16 women, aged 65-83 years) who were diagnosed at over 65 years of age. The patients were divided into two groups (group A: 12 patients diagnosed before 1990; group B: 42 patients diagnosed after 1990) because after 1990, based on growing evidence from large-scale, randomized clinical studies, we intentionally increased the use of angiotensin-converting enzyme inhibitors (ACEI) and then beta-blockers at our hospital. RESULTS: There were no significant differences in age, gender, NYHA functional class, and the prevalence of atrial fibrillation and ventricular tachycardia between the two groups. Left ventricular (LV) size assessed by echocardiography was larger (LV end-diastolic diameter, 67+/-5.9 versus 62+/-6.6 mm; p=0.039) and LV ejection fraction measured by left ventriculography was lower (ejection fraction, 24+/-9 versus 35+/-10%; p=0.004) in group A. ACEI/angiotensin II type 1 receptor blockers (ARB) (0% versus 88%) or beta-blockers (0% versus 52%) were more frequently used in group B. Antiarrhythmics (class Ia or Ib) (75% versus 14%) were less often used in group B. The 5- and 10-year event-free survival rates for cardiac death were 75.4% and 22.0% in group A versus 81.2% and 71.3% in group B (log-rank test, p=0.014). CONCLUSIONS: The prognosis of DCM patients in the elderly has significantly improved over the past 20 years. The advances in the pharmacologic treatment and earlier diagnosis may have contributed to the better survival.

Long-term prognosis of dilated cardiomyopathy revisited: an improvement in survival over the past 20 years.

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.