Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum.

AIMS: We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40-49%]. METHODS AND RESULTS: In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow-up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient-years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient-years in HFrEF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75-0.91; P < 0.001], 7.4 vs. 9.7 per 100 patient-years in HFmrEF (HR 0.76, 95% CI 0.61-0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient-years in HFpEF (HR 0.95, 95% CI 0.79-1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58-0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33-0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59-1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%. CONCLUSION: Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF. ClinicalTrials.gov: CHARM Alternative NCT00634400, CHARM Added NCT00634309, CHARM Preserved NCT00634712

N-terminal pro-B-type natriuretic peptide and prognosis in Caucasian vs. Asian patients with heart failure

Aims N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the most frequently used biomarker in heart failure (HF), but its prognostic utility across ethnicities is unclear. Methods and results This study included 546 Caucasians with HF from the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure and 578 Asians with HF from the Singapore Heart Failure Outcomes and Phenotypes study. NT-proBNP was measured at discharge after HF hospitalization. The studied outcome was a composite of all-cause mortality and HF hospitalization at 18 months. Compared with Caucasian patients, Asian patients were younger (63 +/- 12 vs. 71 +/- 11 years); less often female (26% vs. 39%); and had lower body mass index (26 vs. 27 kg/m(2)), better renal function (61 +/- 37 vs. 54 +/- 20 mL/min/1.73 m(2)), lower rates of atrial fibrillation (25% vs. 46%), strikingly higher rates of diabetes (59% vs. 30%), and higher rates of hypertension (76% vs. 44%). Despite these clear inter-group differences in individual drivers of NT-proBNP, average levels were similar in Asians [2709 (1350, 6302) pg/mL] and Caucasians [2545 (1308, 5484) pg/mL] (P = 0.514). NT-proBNP was strongly associated with outcome [hazard ratio 1.28 (per doubling), 95% confidence interval 1.18-1.39, P <0.001], regardless of ethnicity (P-interaction = 0.719). NT-proBNP was similarly associated with outcome in HF with reduced and preserved ejection fraction in Asian (P-interaction = 0.776) and Caucasian patients (P-interaction = 0.558). Conclusions NT-proBNP has similar prognostic performance in Asians and Caucasians with HF despite ethnic differences in known clinical determinants of plasma NT-proBNP

Facts and numbers on epidemiology and pharmacological treatment of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a major and growing public health problem. Epidemiologic studies demonstrated that heart failure (HF) can be clinically diagnosed in patients with normal or preserved left ventricular ejection fraction. These patients are therefore termed as having HFpEF. In the past, this was often called diastolic HF. Because of the permanent increase of the prevalence of HFpEF during the past decades, HFpEF now accounts for more than 50% of the total HF population. There are uncertainties and debates regarding the definition, diagnosis, and pathophysiology with the consequence that all outcome trials performed so far used criteria for inclusion and exclusion that were not consistent. These trials also failed to document improved prognosis. Recent smaller proof‐of‐concept or Phase II clinical trials investigating different pathophysiological approaches with substances such as the neprilysin inhibitor–angiotensin receptor blocker− combination (LCZ 696), ranolazine, or ivabradine were successful to improve biomarkers, haemodynamics, or functional capacity. Future trials will need to document whether also prognosis can be improved