May 2018 at a Glance: The Central Role of Co-Morbidities

Co-morbidities play a central and increasing role in patients with heart failure (HF) due to aging of these subjects,1, 2 and have a major impact on the clinical course of HF patients. Some of the most promising new drugs for HF may actually come from their treatment.3, 4 Up to 30–40% of patients with HF have type 2 diabetes mellitus. Diabetes worsens cardiac function and patient outcomes. Different antidiabetic drugs have different effects on the clinical course of patients with HF.5-9 These and other aspects make particularly worthwhile and welcome the Heart Failure Association position statement about diabetes and HF,10 which provides an in-depth summary and discussion of all major aspects regarding the interaction between diabetes and HF and the effects of treatment on the clinical course of these two conditions.10 Generally, insulin is not considered as having a meaningful impact on the clinical course of HF.9 Cosmi et al.11 examined two datasets including 24 012 patients with HF from four large randomized trials and 4 million subjects from an administrative database, 103 857 of whom with HF. Multivariable analyses showed an association between insulin treatment and higher all-cause mortality [hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.16–1.38] and HF hospitalizations (HR 1.23, 95% CI 1.13–1.33) in the four trials with even more significant results in the administrative database (HR 2.02, 95% CI 1.87–2.19 and HR 1.42, 95% CI 1.32–1.53, respectively).11 Although these are retrospective analyses, they show the need for antidiabetic drugs which may have favourable effects on HF outcomes. Obese patients with HF and preserved ejection fraction have a peculiar phenotype characterized by increased plasma volume, more concentric left ventricular hypertrophy, greater right ventricular dilatation and dysfunction, increased epicardial fat thickness, increased total heart volume, and heightened ventricular interdependence.12 In his review, Packer shows how neurohormonal mechanisms may cause these abnormalities. Adipocytes secrete many adipokines, including aldosterone, neprilysin and leptin which, both directly and through increased renal sympathetic nerve activity and beta2-adrenergic receptor activation, lead to sodium retention, systemic inflammation, and cardiac fibrosis.13 Accordingly, recent analyses show that obese patients with HF are more likely to benefit from mineralocorticoid receptor antagonist treatment.14 The incidence of cancer may be increased in patients with HF, and the coexistence of these two conditions causes specific challenges for the treatment and follow-up of either cancer and HF.15 These topics are reviewed by Ameri et al.16 in this issue of the Journal. Outcome of patients with HF is comparable with that of the most frequent cancers.17 Fornaro et al.18 compared the outcomes of anthracycline-induced cardiomyopathy with that of idiopathic dilated cardiomyopathy in 67 and 448 patients, respectively, followed for 7.6 ± 5.5 and 8.1 ± 5.5 years. In both cohorts, 25% of patients reached the combined endpoint of death/heart transplantation and survival rates were similar.18 Hoes et al.19 studied human embryonic stem cell-derived cardiomyocytes depleted of iron by incubation with the iron chelator deferoxamine. Their study shows that iron deficiency can directly impair cardiac function with a reduction in cellular ATP levels by 74%, contractile force by 43% and in the maximum velocities during both systole and diastole by 64% and 85%, respectively. These effects were mediated by impaired mitochondrial respiration and could be reversed by the restoration of intracellular iron levels. Beusekamp et al.20 assessed the interaction between serum potassium levels and the dose of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort. Baseline potassium was an independent predictor of lower ACEi/ARB dosage (HR 0.70, 95% CI 0.51–0.98), although an increase in potassium was not associated with adverse outcomes and did not attenuate the beneficial effects of ACEi/ARB uptitration.