Hemodynamic Characteristics and Predictors of Pulmonary Hypertension in Patients With Sickle Cell Disease

Abstract

Pulmonary hypertension (PH) is a common comorbidity of sickle cell disease (SCD) with an associated increased mortality risk, but its etiology is not well-understood. To evaluate the hemodynamic characteristics, clinical predictors, and cardiovascular manifestations of elevated pulmonary arterial pressure in this population, we performed noninvasive hemodynamic assessments of 135 patients with SCD using Doppler echocardiography. A diagnosis of PH was based on gender-, age-, and body mass index (BMI)-specific normal reference ranges for tricuspid regurgitation jet velocities (TRV). A high TRV was noted in 34 (25%) of patients. Pulmonary vascular resistance (PVR) was elevated in only 2 of the 34 patients (6%) with suspected PH, but was significantly higher than in those with a normal TRV. In univariate regression, TRV correlated with age, BMI, left atrial pressure, and right ventricular stroke volume, and was negatively associated with hemoglobin and glomerular filtration rate. Left atrial pressure, right ventricular stroke volume, and hemoglobin remained independent predictors of TRV in a multivariate model. A higher TRV was also associated with larger right ventricular and right atrial chamber sizes and higher N-terminal pro-brain natriuretic peptide levels. Our results suggest that the mild elevation in TRV often observed in patients with SCD is rarely associated with a high PVR, and that multiple factors – including the compensatory high output state associated with anemia, pulmonary venous hypertension, and a pulmonary vasculopathy – may contribute to an elevated pulmonary arterial pressure in these patients.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

“…Mildly increased systolic pulmonary arterial pressure (PAP) estimated by tricuspid regurgitant jet velocity (TRV) of >2.5 m/s by echocardiography has been shown to be an independent risk factor for early mortality (odds ratio 8-15) (5,(15)(16)(17)(18)(19)(20). This finding was initially considered to be consistent with pulmonary arterial hypertension (PH) (5,17,(21)(22)(23)(24)(25). However, right heart catheterization studies show that only 25-30% of patients with TRV ≥ 2.5 m/s truly have PH, with the majority having pulmonary venous hypertension (18,(26)(27)(28)(29).…”

Exercise‐Induced Abnormal Increase of Systolic Pulmonary Artery Pressure in Adult Patients With Sickle Cell Anemia: An Exercise Stress Echocardiography Study

“…SPAP was calculated from the modified Bernoulli equation (SPAP = 4 × TRV2 + RAP), where RAP is the right atrial pressure, assumed to be 5 mmHg for all patients. At rest, PH in SCA young adult patients and controls was defined as TRV ≥2.5 m/sec as reported by others …”

Assessment of Ventricular Function in Adults with Sickle Cell Disease: Role of Two-Dimensional Speckle-Tracking Strain

“…There are some possible explanations for RV dysfunction in SCD, including LV diastolic dysfunction 3,39 and elevation of pulmonary pressure due to increased cardiac output, rather than to increased pulmonary vascular resistance. 22,32,40 Airway hyperactivity and sleep-disordered breathing have also been mentioned as etiologic factors. 3,41 In the present study, no RV dysfunction was detected using conventional echocardiographic methods, including M-modederived tricuspid annular motion, RV fractional area change, and tissue Doppler imaging, and speckle-tracking strain for additional information beyond standard measurements.…”