Diabetes mellitus is associated with low exercise capacity and impaired peripheral vasodilation in patients with heart failure - a propensity score-matched study.

AIMS: Diabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity. METHODS AND RESULTS: The Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO2 (15.7 [13.0-19.1] vs. 17.3 [14.1-21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85-0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93-1.02). A similar heterogeneity was also observed for HDL cholesterol. CONCLUSIONS: Diabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM.

Biological basis and treatment of frailty and sarcopenia.

In an ageing society, the importance of maintaining healthy life expectancy has been emphasized. As a result of age-related decline in functional reserve, frailty is a state of increased vulnerability and susceptibility to adverse health outcomes with a serious impact on healthy life expectancy. The decline in skeletal muscle mass and function, also known as sarcopenia, is key in the development of physical frailty. Both frailty and sarcopenia are highly prevalent in patients not only with advanced age but also in patients with illnesses that exacerbate their progression like heart failure (HF), cancer, or dementia, with the prevalence of frailty and sarcopenia in HF patients reaching up to 50-75% and 19.5-47.3%, respectively, resulting in 1.5-3 times higher 1-year mortality. The biological mechanisms of frailty and sarcopenia are multifactorial, complex, and not yet fully elucidated, ranging from DNA damage, proteostasis impairment, and epigenetic changes to mitochondrial dysfunction, cellular senescence, and environmental factors, many of which are further linked to cardiac disease. Currently, there is no gold standard for the treatment of frailty and sarcopenia, however, growing evidence supports that a combination of exercise training and nutritional supplement improves skeletal muscle function and frailty, with a variety of other therapies being devised based on the underlying pathophysiology. In this review, we address the involvement of frailty and sarcopenia in cardiac disease and describe the latest insights into their biological mechanisms as well as the potential for intervention through exercise, diet, and specific therapies.

Bone status in men with heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

AIM: To assess bone status expressed as hip bone mineral density (BMD) in men with heart failure (HF). METHODS AND RESULTS: A total of 141 male patients with HF underwent dual energy X-ray absorptiometry to assess their BMD. We analysed markers of bone metabolism. Patients were classified as lower versus higher BMD according to the median hip BMD (median = 1.162 g/cm2 ). Survival was assessed over 8 years of follow-up. Patients with lower BMD were older (71 ± 10 vs. 66 ± 9 years, p = 0.004), more likely to be sarcopenic (37% vs. 7%, p < 0.001) and to have lower peak oxygen consumption (absolute peak VO2 1373 ± 480 vs. 1676 ± 447 ml/min, p < 0.001), had higher osteoprotegerin and osteocalcin levels (both p < 0.05) compared to patients with higher BMD. Among 47 patients with repeated BMD assessments, a significant reduction in BMD was noted over 30 months of follow-up. In multivariate logistic regression analysis, serum osteocalcin remained independently related with lower BMD (odds ratio [OR] 1.738, 95% confidence interval [CI] 1.136-2.660, p = 0.011). Hip BMD and serum osteoprotegerin were independent predictors of impaired survival on Cox proportional hazard analysis (hazard ratio [HR] 0.069, 95% CI 0.011-0.444, p = 0.005, and HR 0.638, 95% CI 0.472-0.864, p = 0.004, respectively). CONCLUSIONS: Patients with HF lose BMD over time. Markers of bone turnover can help in identifying patients at risk with osteocalcin being an independent marker of lower hip BMD and osteoprotegerin an independent predictor of death. HF patients with increased osteocalcin and osteoprotegerin may benefit from BMD assessment as manifest osteoporosis seems to be too late for clinically meaningful intervention in HF.

Sarcopenia and Frailty in Heart Failure: Is There a Biomarker Signature?

PURPOSE OF REVIEW: Sarcopenia and frailty are common in patients with heart failure (HF) and are strongly associated with prognosis. This review aims to examine promising biomarkers that can guide physicians in identifying sarcopenia and frailty in HF. RECENT FINDINGS: Traditional biomarkers including C-reactive protein, aminotransaminase, myostatin, and urinary creatinine as well as novel biomarkers including microRNAs, suppression of tumorigenicity 2 (ST2), galectin-3, and procollagen type III N-terminal peptide may help in predicting the development of sarcopenia and frailty in HF patients. Among those biomarkers, aminotransferase, urinary creatinine, and ST2 predicted the prognosis in HF patients with sarcopenia and frailty. This review outlines the current knowledge of biomarkers that are considered promising for diagnosing sarcopenia and frailty in HF. The listed biomarkers might support the diagnosis, prognosis, and therapeutic decisions for sarcopenia and frailty in HF patients.