Cardiopulmonary Hemodynamic Determinants of Long-Term Survival in Sickle Cell Disease: Insights from the ETENDARD Study.

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.