Pulmonary vascular disease due to left heart disease: how to achieve a more accurate approach beyond the haemodynamic phenotype.

Abstract

We read with interest the article published by Palazzini et al. looking at the analysis of survival in pulmonary hypertension due to left heart disease (PH-LHD) according to the haemodynamic phenotype definitions of the ESC/ERS guidelines.1 Patients with an isolated increase in pulmonary vascular resistance or diastolic pulmonary gradient (indeterminate phenotype) had a worse prognosis compared with patients with both normal parameters [isolated post-capillary pulmonary hypertension (Ipc-PH)] and a similar survival to that of patients with a concomitant increase in both parameters [combined pre- and post-capillary pulmonary hypertension (Cpc-PH)]. Although the patients with indeterminate phenotype seem to have an intermediate haemodynamic profile compared with Ipc-PH and Cpc-PH patients, the cardiac index is similar to that of patients with Cpc-PH, which could explain the similar worse prognosis due to the presence of right ventricular dysfunction. It is noteworthy that the proportions of valvular heart disease, heart failure with preserved and reduced ejection fraction in the different haemodynamic subgroups (Ipc-PH, intermediate and Cpc-PH) are similar, which could explain the apparent absence of influence of LHD aetiology on prognosis. Many efforts have been made to achieve the appropriate combination and cut-off values of haemodynamic parameters to define the different subsets of PH-LHD.2 The authors have proposed that Ipc-PH patients may be at low probability, and Cpc-PH may be at high probability for pulmonary vascular disease (PVD).3 However, the accuracy to predict the severity and reversibility of PVD in patients with PH-LHD continues to be a matter of debate.3 What begins as a passive retrograde transmission of left atrial pressure continues with the loss of the vasodilatory capacity and the anatomical and functional remodelling of the pulmonary arteries. The concomitant haemodynamic and intravascular ultrasound examinations allow to estimate pulmonary artery stiffness by the elastic modulus [EM: pulse pulmonary arterial pressure x diastolic lumen area/(systolic – diastolic lumen area)] and to assess the relative area of wall thickness as: (external sectional area – intimal area)/external cross-sectional area x 100.4 The PVD may be a continuum. In a cohort of patients with persistent pulmonary hypertension after mitral valve replacement, all patients showed a significant increase of EM beyond the haemodynamic phenotype (control patients 21 ± 2, Ipc-PH 124 ± 5.6, indeterminate 166 ± 22, Cpc-PH 221 ± 54 mmHg).5 Interestingly, the haemodynamic response to inhaled nitric oxide was significantly correlated with EM (Δstroke volume, r = 0.698; Δpulmonary capacitance, r = 0.67; Δtotal pulmonary resistance, r = –0.85).6 These emerging data justify randomized trials focusing on more strict subgroup definitions to achieve significant therapeutic progress in PH-LHD patients.