Sarcopenia, one of the extracardiac factors for reduced functional capacity and poor outcome in heart failure (HF), may act differently between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to investigate the impact of sarcopenia on mortality in HFpEF and HFrEF. We performed a post hoc analysis of a multicentre prospective cohort study, including 942 consecutive older (age ≥65 years) hospitalized patients: 475 with HFpEF (ejection fraction ≥45%, age 81 ± 7 years, 48.8% men) and 467 with HFrEF (ejection fraction <45%, age 78 ± 8 years, 68.1% men). Sarcopenia was diagnosed according to the international criteria incorporating muscle strength (handgrip strength), physical performance (gait speed), and skeletal muscle mass (appendicular skeletal mass). The HFpEF group consisted of fewer patients with low appendicular skeletal muscle mass index measured using bioelectrical impedance analysis [<7.0 kg/m² (men) and <5.7 (women); 22.1% vs. 31.0%, P = 0.003], and more patients with low handgrip strength [<26 kg (men) and <18 (women); 67.8% vs. 55.5%, P < 0.001], and slow gait speed [<0.8 m/s (both sexes); 54.5% vs. 41.1%, P < 0.001] than the HFrEF group, resulting in a similar sarcopenia prevalence in the two groups (18.1% vs. 21.6%, P = 0.191). Sarcopenia was an independent predictor of 1-year mortality in both HFpEF and HFrEF [hazard ratio (95% confidence interval) 2.42 (1.36–4.32), P = 0.003 in HFpEF and 2.02 (1.08–3.75), P = 0.027 in HFrEF; P for interaction = 0.666] after adjustment for other predictors. In older patients with HF, sarcopenia contributes to mortality similarly in HFpEF and HFrEF.

Research and development of new drugs requires both long time and high costs, whereas safety and tolerability profiles make the success rate of approval very low. Drug repurposing, applying known drugs and compounds to new indications, has been noted recently as a cost-effective and time-unconsuming way in developing new drugs, because they have already been proven safe in humans. In this review, we discuss drug repurposing of approved cardiovascular drugs, such as aspirin, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, cardiac glycosides and statins. Regarding anti-tumor activities of these agents, a number of experimental studies have demonstrated promising pleiotropic properties, whereas all clinical trials have not shown expected results. In pathological conditions other than cancer, repurposing of cardiovascular drugs is also expanding. Numerous experimental studies have reported possibilities of drug repurposing in this field and some of them have been tried for new indications (‘bench to bedside’), while unexpected results of clinical studies have given hints for drug repurposing and some unknown mechanisms of action have been demonstrated by experimental studies (‘bedside to bench’). The future perspective of experimental and clinical studies using cardiovascular drugs are also discussed.

Japan has the highest proportion of older people in the world, 25.9% of the population were aged 65 or above in 2014. Although there have been no population-based studies that precisely examined the prevalence of heart failure in Japan, one report estimated the number of Japanese outpatients with left ventricular dysfunction was 979, 000 (0.8% of total population), which was projected to increase gradually as the population ages, reaching 1.3 million by 2030. Ischemic etiology was less frequently observed in Japan (31–47%) than in western population (54–57%). The prevalence of HF with preserved ejection fraction was similar between Japan (34–68%) and western countries (34–51%). Non-cardiac co-morbidities such as chronic obstructive pulmonary diseases and anemia were observed in 6–9% in Japan and 19–31% in western countries, and 35–58% in Japan and 37–56% in western countries, respectively. The definition of chronic kidney disease widely differed among studies. A relatively good survival prognosis in Japanese patients has been discussed. One-year mortality after discharge from initial hospitalization was 9–12%, which seems to be better than the western cohort. Although length of stay was remarkably longer in Japan (15–21 days) than western countries (4–9 days), it will have to be shortened, as Japan is now being faced with an upcoming HF pandemic. Some treatments in Japan are not approved outside Japan. Such treatments include carperitide infusion (used in 58% of hospitalized HF), nicorandil infusion (9.6%), and oral pimobendan (5%). More recently, landiolol and tolvaptan have been approved. Although these drugs might have a potential to be an effective therapeutic option, lack of corroborating evidence in many of such treatments would emphasize the need for larger clinical trials.

Background: Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF. Methods: This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid‐range LVEF (40–50%), and reduced (<40%) LVEF, respectively. Dual‐energy X‐ray absorptiometry was performed with the patients in the stable state after decongestion therapy. Results: The mean body mass index of patients was 22.1 ± 4.6 kg/m ² , and the mean appendicular skeletal mass (ASM) index was 6.88 ± 1.23 kg/m ² in men and 5.59 ± 0.92 in women; 54.1% of the patients showed reduced muscle mass defined by the international cut‐off value (7.0 kg/m ² for men and 5.4 for women). The mean fat mass was 20.4 ± 7.2% in men and 27.2 ± 8.6% in women. During a median follow‐up of 37 months, 92 (22.0%) of 418 patients with HF died (1 and 3 year mortality: 8.4% and 17.3%, respectively). Lower values of both skeletal muscle and fat mass were independently associated with increased risk of mortality adjusted for age, sex, haemoglobin, New York Heart Association functional class, and height squared (hazard ratio with 95% confidence interval of 0.825 [0.747–0.908] per 1 kg increase of ASM, P < 0.001, and 0.954 [0.916–0.993] per 1 kg increase of fat mass, P = 0.018, respectively). Conclusions: More than half of the patients with HF showed reduced muscle mass. Lower values of both muscle and fat mass were associated with higher mortality in HF.

Impaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS. A total of 417 patients with ACS who received reperfusion wore a continuous glucose monitoring system (CGMS) in a stable phase after admission and were monitored for at least 24 consecutive h. The mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. We divided into two groups based on the highest tertile levels of MAGE (MAGE = 52 mg/dl). The groups were followed up for a median of 39 months [IQR 24–50 months]. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE). During follow-up, 66 patients experienced MACCE (5 patients had cardiovascular death, 14 had recurrence of ACS, 27 had angina requiring revascularization, 8 had acute decompensated heart failure, and 16 had a stroke). MACCE was more frequently observed in the high MAGE group (23.5% vs. 11.6%, p = 0.002). In multivariate analysis, high MAGE was an independent predictive factor of poor prognosis for MACCE (odds ratio, 1.84; 95% confidence interval, 1.01–3.36; p = 0.045). Glycemic variability determined with a CGMS is a predictor of prognosis in patients with ACS without severe DM. Trial registration UMIN 000010620. Registered April 1st 2012

Even though most clinical data on cachexia have been reported from Western countries, cachexia may be a growing problem in Asia as well, as the population in this area of the world is considerably larger. Considering the current definitions of obesity and sarcopenia in Japan, which are different from the ones in Western countries, the lack of a distinct cachexia definition in Japan is strinking. Only one epidemiological study has reported the prevalence of cachexia using weight loss as part of the definition in patients with stage III or IV non‐small cell lung cancer. Although the reported prevalence of 45.6% is within the range of that in Western countries (28–57% in advanced cancer), we cannot compare the prevalence of cachexia in other types of cancer, heart failure, chronic obstructive pulmonary disease (COPD), and kidney disease (CKD) between Japan and Western countries. In patients with heart failure, one third of Japanese patients has a body mass index <20.3 kg/m² whereas the prevalence of underweight is 13.6% in reports from Western countries. These results may suggest that there are more cachectic heart failure patients in Japan, or that using the same definition like Western countries leads to gross overestimation of the prevalence of cachexia in Japan. The rate of underweight patients in COPD has been reported as 31–41% in COPD and seems to be high in comparison to the prevalence of cachexia in Western countries (27–35%). The reported lowest quartile value of BMI (19.6 kg/m²) in CKD may match with the prevalence of cachexia in Western countries (30–60%). The number of clinical trials targeting cachexia is very limited in Japan so far.