From PARADIGM to PARAGON further evidence supporting continuous heart failure spectrum

Neurohormonal inhibitors form the backbone of treatment in heart failure (HF) with low left ventricular ejection fraction (LVEF).1 In contrast, treatment of HF with near-normal/normal LVEF2 is based on expert consensus focused on congestion and comorbidity management.3 The usefulness of LVEF as a discriminator of HF phenotypes has been challenged and it has been suggested that HF is a syndrome across a continuous LVEF spectrum with varying degrees of neurohormonal activation and response to treatment.4,5 The continuous HF spectrum concept is further supported by several large-scale randomized trials, which demonstrated that HF patients with an LVEF of 40–50% have similar clinical features as those with a LVEF < 40%.6 The recent pooled analysis of two trials,7 the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial8 and the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial,9 further strengthens one of the pivotal notions of the continuous HF spectrum concept, namely that neurohormonal overactivity and consequently the effectiveness of neurohormonal modulating agents, progressively decline as LVEF increases but both remain measurable at higher LVEF.