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.

The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. We measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15mm). Two patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6-17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation.

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.

Aims: Hypertrophic cardiomyopathy (HCM) is generally associated with mild disability and normal life expectancy. On the other hand, once the end-stage phase of HCM characterized by left ventricular (LV) ejection fraction < 50% is established, patients with this subtype have a poor prognosis. This study clarifies the clinical parameters associated with progression to end-stage HCM. Methods and results: We retrospectively studied 157 HCM patients (age 59.9 ± 14.2 years, 104 men) with preserved LV systolic function in whom subsequent echocardiographic data were obtained for a period of >1 year. HCM progressed to end-stage HCM in 13 patients (8.3%) of the 157 patients during a mean follow-up period of 6.3 ± 2.8 years. Compared with patients who did not reach end-stage HCM at the last evaluation, patients with progression to the end-stage phase had lower ejection fraction, larger LV size, more enlarged left atrial diameter, longer follow-up period, and higher frequency of an elevated concentration of high-sensitivity cardiac troponin T (hs-cTnT; >0.014 ng/mL) at registration. Multivariate analysis revealed that elevated hs-cTnT was a significant predictor independent of lower LV ejection fraction for progression to end-stage HCM. Furthermore, in patients with elevated hs-cTnT levels, LV ejection fraction became significantly lower, LV end-diastolic diameter increased, and LV wall thickness decreased during the follow-up period, whereas those parameters did not change in the normal hs-cTnT group. Conclusions: In patients with HCM, an elevated hs-cTnT was associated with progression of LV remodelling, and this biomarker can be useful for predicting progression to the end-stage phase.

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.