Cardiopulmonary Hemodynamic Determinants of Long-Term Survival in Sickle Cell Disease: Insights from the ETENDARD Study
Laurent Savale, Thomas d’Humières, Athénaïs Boucly, Anoosha Habibi, François Lionnet, Gylna Loko, Jocelyn Inamo, Gonzalo De Luna, Salma Al Khaf, Christelle Chantalat‐Auger, Bernard Maître, Xavier Jaïs, David Montani, Olivier Sitbon, Florence Parent, G Simonneau, Frederic Galactéros, Étienne Audureau, Pablo Bartolucci, Marc Humbert
Abstract
Abstract Rationale Pulmonary hypertension is a serious cardiopulmonary complication of sickle cell disease, but the prognostic impact of hemodynamic parameters remains poorly defined. Objectives This study aimed to assess the clinical and long-term prognostic relevance of hemodynamic parameters in sickle cell disease. Methods Data were analyzed from the French ETENDARD cohort. All 398 participants underwent echocardiography; those with tricuspid regurgitation velocity ≥2.5 m/s proceeded to right heart catheterization. Over a minimum 10-year follow-up, we examined the clinical and prognostic significance of hemodynamic variables. Measurements and Main Results Pulmonary hypertension defined by a mean pulmonary arterial pressure (mPAP) >20 mm Hg was identified in 44 patients (11%). Among them, 26 (6.5%) had a pulmonary arterial wedge pressure ≤15 mm Hg, and 18 (4.5%) had a pulmonary arterial wedge pressure >15 mm Hg. Mortality during follow-up was 11.1%. A significant association was found between pulmonary vascular resistance (PVR) levels and mortality risk, with a threshold identified at 1.5 Wood units (WU) through receiver operating characteristic curve analyses. In patients with mPAP >20 mm Hg and PVR ≥1.5 WU, the adjusted hazard ratio for mortality was 4.27 (95% confidence interval, 1.88–9.74; P < 0.001). A hemolytic phenotype and the presence of systemic complications, including hypertension, left ventricular diastolic dysfunction, renal impairment, and leg ulcers, were associated with elevated PVR and increased mortality risk. Conclusions A PVR threshold of 1.5 WU emerges as a key predictor of mortality in patients with an mPAP above 20 mm Hg, particularly when assessed in conjunction with markers of hemolysis and systemic complications.