November 2020 at a glance: focus on comorbidities and medical treatment.

Abstract

The role of glycaemic control in patients with heart failure (HF) and concomitant diabetes is controversial. Insulin treatment is associated with poorer outcomes in these patients.1, 2 McAlister et al.3 investigated the relationship between glycaemic control, i.e. glycated haemoglobin (HbA1c), and cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus and atherosclerosis from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Results showed a U-shaped association between baseline HbA1c and CV outcome, with the lowest risk when HbA1c was around 7%.3 Iron deficiency impairs cardiac contractility through decreased mitochondrial function.4 Hirsch et al.5 assessed iron concentrations in non-ischaemic HF with reduced ejection fraction (HFrEF), using endomyocardial biopsies. Lower iron concentrations were associated with a greater severity of HF. Hyperkalaemia is frequent in HFrEF patients, above all when on renin–angiotensin–aldosterone system inhibitors.6, 7 An administrative database analysis showed the association of hyperkalaemia with mortality and CV events in HF patients on renin–angiotensin–aldosterone system inhibitors.8 In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, both hypokalaemia and hyperkalaemia were associated with a higher risk of CV death, compared with potassium levels between 4.1 and 4.9 mmol/L (hazard ratio 2.40 and 1.42, respectively). No interaction between serum potassium and sacubitril/valsartan efficacy vs. enalapril was found.9 Frailty is a major independent determinant of outcomes in HF.10 A new Frailty Score has recently been developed.11 The FRAGILE-HF study was a prospective multicentre study investigating the prevalence, overlap, and prognostic implications of physical and social frailties and cognitive dysfunction in patients hospitalized with HF. Patients with a greater number of frailty domains had higher mortality and HF rehospitalization.12 The prevalence of frailty is increased in HF with preserved ejection fraction (HFpEF) patients and is associated with worse outcome.13 Similarly, frailty was highly prevalent in HFrEF patients and was associated with poor quality of life and outcomes in a retrospective analysis of PARADIGM-HF and ATMOSPHERE.14 Biomarkers, namely natriuretic peptides, play a major role in the management of HF.15 Aimo et al.16 analysed the prognostic value and the influence of age on circulating levels of biomarkers in 5301 patients with chronic HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predicted outcomes. sST2 was less influenced by age than the other two biomarkers. In the Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trial, serum uric acid (SUA) was an independent predictor of poor outcome in HFpEF. Sacubitril/valsartan reduced SUA levels and the need for SUA-related drugs.17 Sex-based differences in biomarkers, health status, and reverse cardiac remodelling in HFrEF patients treated with sacubitril/valsartan in the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodelling During Entresto Therapy for HF (PROVE-HF) were analysed by Ibrahim et al.18 Sex is a major determinant of clinical characteristics and outcomes in patients with HFrEF and HFpEF.19-21 In the study by Ibrahim et al.18, women treated with sacubitril/valsartan had more rapid reduction in NT-proBNP plasma levels and reverse cardiac remodelling and a larger improvement in quality of life. McEwan et al.22 showed the cost-effectiveness of dapagliflozin for the treatment of HFrEF with significant life-year and quality-adjusted life-year gains for the patients treated. The Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in HF (GALACTIC-HF) trial assessed the safety and efficacy of the cardiac myosin activator omecamtiv mecarbil in HFrEF patients. The baseline characteristics of enrolled patients are presented in this issue. The trial enrolled well-treated and high-risk inpatients and outpatients, representative of recent HF registries and trials.23