September 2020 at a glance: focus on heart failure with preserved ejection fraction and medical therapy.

Abstract

Type 2 diabetes mellitus and obesity increase heart failure (HF) risk.1-4 Dang et al.5 showed that delivery of longevity-associated variant of the human BPIFB4 gene in obese mice with diabetes improves cardiac function. Usefulness of biomarker measurements may be lower in patients with HF and preserved ejection fraction (HFpEF).6, 7 Henkens et al.8 performed a systematic review of studies investigating the diagnostic value of novel biomarkers for HFpEF. The risk of bias was high in all studies. The main limitations were use of case-control designs, poor diagnosis of HFpEF, absence of pre-specified cut-off points, lack of external validation, inadequate and variable reference standards. An analysis of TOPCAT Americas showed that spironolactone treatment was associated with a reduction in loop diuretic and thiazide doses. The reduction in the risk of HF hospitalizations with spironolactone (hazard ratio 0.77, 95% confidence interval 0.62–0.96; P = 0.021) was, however, independent of multiple variables, including loop diuretic dose and serum creatinine, thus showing it was not mediated by its diuretic effects.9 Elderly age, renal dysfunction and hyperkalaemia are major causes of spironolactone discontinuation.10 An analysis of TOPCAT Americas confirmed these data and also showed that these patients received lower spironolactone, but not placebo, doses. Spironolactone reduced the primary endpoint also in these subgroups while its withdrawal was associated with a two to four-fold higher risk of events. Thus, a low-dose strategy should be preferred instead of discontinuation.11 Larsen et al.12 showed that metformin can improve myocardial efficiency in insulin-resistant patients with HFrEF without diabetes. Sacubitril/valsartan improves outcome in HFrEF.13 An analysis of PARADIGM-HF showed that liver dysfunction is an independent predictor of outcomes in HFrEF patients and sacubitril/valsartan improved liver function, compared with enalapril.14 Oxidative stress and inflammation have a key role in HF.15 Vericiguat treatment was associated with reduction in inflammatory- and oxidative stress-related markers, such as high-sensitivity C-reactive protein and uric acid, and this may have a role for its beneficial effects.16 Inotropic drugs did not improve survival in HF.17, 18 Better results can be expected from drugs not acting through an increase in intracellular calcium. Danicamtiv, a novel cardiac myosin activator, improved stroke volume, global longitudinal and circumferential strain and left atrial function in experimental models and in a phase 2a trial in patients with HFrEF.19 In patients hospitalized for acute HF, istaroxime had beneficial effects on left ventricular function, without hypotension, tachycardia, or serious cardiac adverse events.20 Lung congestion is a leading cause of dyspnoea and exercise intolerance.21 Transient receptor potential vanilloid 4 (TRPV4) channel regulates fluid exchange in the lungs. A novel transient TRPV4 antagonist (GSK2798745) was tested in a pilot randomized, placebo-controlled trial aimed at the reduction of lung water content. The new drug was well tolerated and showed a trend towards improved gas transfer.22