SOPRANO: Macitentan in Patients With Pulmonary Hypertension Following Left Ventricular Assist Device Implantation

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] \u3e3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan (n = 28) or placebo (n = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58–0.94; p = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR 40.0% receiving placebo (p = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903

The Nuts and Bolts of Interpreting Hemodynamics in Pulmonary Hypertension Associated With Diastolic Heart Failure

With the widespread application of transthoracic echocardiography as a screening tool for pulmonary hypertension (PH), we have come to appreciate the prevalence of PH associated with diastolic heart failure. Diastolic heart failure (DHF, sometimes called heart failure with preserved, or normal, left ventricular ejection fraction [HFpEF]) is quite common, and PH appears to be a fairly frequent component of DHF.1–3 The epidemiology of these conditions is described in the article by Dr Soto in this issue of Advances. There is a complex relationship between DHF and PH: the 2 may exist independent of each other or in combination; and when they exist in combination, the PH may be in proportion or out of proportion to the DHF. Cardiac catheterization is critical in differentiating among these patterns, and this distinction may lead to important modifications in treatment strategy. This requires, however, a full understanding of the proper performance and interpretation of cardiac catheterization, as well as the potential pitfalls that can limit the utility of the procedure. This article will discuss these aspects of cardiac catheterization as they pertain to patients with pulmonary arterial hypertension (PAH) and PH associated with DHF. A number of important aspects of cardiac catheterization are not covered here due to space limitations but can be obtained in a more detailed text.4</jats:p

Pulmonary Hypertension in the Intensive Care Unit

Pulmonary hypertension occurs as the result of disease processes increasing pressure within the pulmonary circulation, eventually leading to right ventricular failure. Patients may become critically ill from complications of pulmonary hypertension and right ventricular failure or may develop pulmonary hypertension as the result of critical illness. Diagnostic testing should evaluate for common causes such as left heart failure, hypoxemic lung disease and pulmonary embolism. Relatively few patients with pulmonary hypertension encountered in clinical practice require specific pharmacologic treatment of pulmonary hypertension targeting the pulmonary vasculature. Management of right ventricular failure involves optimization of preload, maintenance of systemic blood pressure and augmentation of inotropy to restore systemic perfusion. Selected patients may require pharmacologic therapy to reduce right ventricular afterload by directly targeting the pulmonary vasculature, but only after excluding elevated left heart filling pressures and confirming increased pulmonary vascular resistance. Critically-ill patients with pulmonary hypertension remain at high risk of adverse outcomes, requiring a diligent and thoughtful approach to diagnosis and treatment. </jats:p