Reply

Abstract

ReplyWe read with great interest the research letter from Emmens et al. 1 and thank the authors for their comments on our recently published paper in this journal. 2 Emmens et al. evaluated relaxin circulating levels in a cohort of patients with heart failure (HF) with preserved ejection fraction (HFpEF) and pulmonary hypertension (PH) and found no association between relaxin groups and echocardiographically or invasively determined intracardiac pressures. 1 These results do not extend our recent findings that relaxin circulating levels were associated with clinical and echocardiographic markers of volume overload, PH and right heart dysfunction and overload in a population of acute HF patients. 2 Several differences between the study populations are worth noting and may help to elucidate the differences between the results of the two studies. We evaluated relaxin levels at admission in a population of patients with acute HF, including both patients with HFpEF and those with HF with reduced ejection fraction. 2 These patients were heterogeneous with respect to the degree of volume overload, volume distribution and echocardiographic parameters of chamber dimensions and function, which allowed us to establish different patterns of pulmonary pressures and right heart overload among relaxin groups. 2 In the study by Emmens et al., 1 all patients had chronic HFpEF with established PH. This patient selection criterion may, on one hand, have hindered the establishment of differences in pulmonary and right heart pressures between groups. However, on the other hand, it supports our hypothesis of increased relaxin secretion to circulation in states of PH as relaxin levels in these patients (median: 82.3 pg/mL) 1 were higher than have .been described in most previous studies addressing relaxin levels in HF, including our own. The lack of relaxin levels below the detection limit of the assay, 1 unlike in our study in which levels were undetectable in about 25% of patients, 2 also strengthens this hypothesis.In line with the promising results of serelaxin clinical trials in HF, 3,4 increasing evidence suggests a role for endogenous relaxin in HF pathophysiology. The hypothesis of a compensatory up-regulation of the relaxin system in states of PH and of a role for this system in the modulation of pulmonary vasculature is compelling based on the available evidence, 2,4,5 but further studies are needed to corroborate it. Better understanding of the role of endogenous relaxin in the pathophysiology of acute and chronic HF may be of great value in terms of expanding the therapeutic use of serelaxin in this context. References1. Emmens JE, ter Maaten JM, Voors AA. Are circulating relaxin levels related to pulmonary hypertension in patients with heart failure? Eur J Heart Fail 2017;19:958-960. 2. Pintalhao M, Castro-Chaves P, Vasques-Novoa F, Goncalves F, Mendonca L, Fontes-Carvalho R, Lourenco P, Almeida P, Leite-Moreira A, Bettencourt P. Relaxin serum levels in acute heart failure are associated with pulmonary hypertension and rig...