Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease.

Abstract

Adults with sickle cell disease have a high prevalence of pulmonary hypertension. This picture is often complicated by concurrent left ventricular diastolic dysfunction and anemia-related changes in hemodynamics. The change in pressure across the pulmonary circulation reflected by the transpulmonary gradient is less clouded by anemia-related adaptations. We characterized the association of elevated transpulmonary gradient with right ventricular structure and function, exercise capacity and mortality. Data from 84 patients (age 41+/-13 years, 55% female [n=46], 82% hemoglobin SS [n=69]) with right heart catheterization from the Bethesda Sickle Cell Cohort were analyzed. Of the 84 patients, forty-one underwent cardiac magnetic resonance imaging within two days of right heart catheterization. Patients with a catheterization-derived transpulmonary gradient ≥12mmHg had more severe symptoms (p=0.013), shorter 6-minute walk distance (p=0.006), lower cardiac index (p<0.001), reduced right ventricular ejection fraction (p=0.002) and cardiac magnetic resonance imaging markers of adverse morphologic adaptation. An RVEF <32% derived from cardiac magnetic resonance predicted decreased survival (HR 3.70, 95% CI 1.04-13.12, p=0.030) and higher New York Heart Association classification (OR 9.29, p=0.018). In a multivariate model controlling for age and phenotype, transpulmonary gradient ≥12mmHg and right ventricular ejection fraction <32% were independently predictive of increased mortality (HR 5.47, 95% CI 1.13-26.42, p=0.035 and HR 5.11, 95% CI 1.13-23.13, p=0.034). Patients with sickle cell disease and elevated transpulmonary gradient have findings of maladaptive RV remodeling on cardiac magnetic resonance imaging. Elevated transpulmonary gradient and cardiac magnetic resonance-derived RV dysfunction independently predict higher mortality in sickle cell disease. Cardiac magnetic resonance may have a useful role in the clinical evaluation and non-invasive prognostication of adults with sickle cell disease and suspected pulmonary hypertension. This clinical trial was registered at clinicaltrials.gov identifier: [NCT00011648][1] NCT00081523, [NCT00023296][2], and [NCT00352430][3]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00011648&atom=%2Fhaematol%2Fearly%2F2015%2F11%2F13%2Fhaematol.2015.125229.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00023296&atom=%2Fhaematol%2Fearly%2F2015%2F11%2F13%2Fhaematol.2015.125229.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00352430&atom=%2Fhaematol%2Fearly%2F2015%2F11%2F13%2Fhaematol.2015.125229.atom