Exercise-Induced Pulmonary Hypertension in Sickle Cell Anemia: a Study with Exercise Stress Echocardiography

Background: Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle cell anemia. Exercise treadmill stress echocardiography (ETSE) is able to detect latent PH.

Objective: To investigate the occurrence of exercise-induced PH in patients with sickle cell anemia and normal pulmonary pressure (PP) at rest, and its relationship with clinical and echocardiographic variables.

Design: observational transversal study.

Patients and Methods: We studied 44 patients (22 men, mean age = 25.3 y.o.) with sickle cell anemia and normal PP at rest (tricuspid regurgitant jet velocity: TRV < 2.5 m/s). They were divided into 2 groups: (G1) normal PP after ETSE (TRV ≤ 2.7 m/s); G2: exercise-induced PH (TRV > 2.7 m/s). The cut off points of TRV at rest and exercise were derived from healthy control subjects, matched for age, sex, and body surface area. Data obtained from ETSE were correlated with clinical, echocardiographic and ergometric variables, including left atrial volume indexed for body surface area and E/E’ ratio derived from pulsed wave and tissue Doppler. Student’s t test e chi-square test were used for statistical analysis. Multivariate logistic analysis was used to determine the independent predictors of abnormal PP response to exercise. Statistical significance was defined as a p < 0.05.

Results: The exercise-induced PH occurred in 57% of patients (G2), with levels of TRV ranging from 2.8 to 4.5 m/s (3.4 ± 0.4m/s), significantly higher than those observed in G1 (2.5 ± 0.3m/s, p < 0.001). Exercise-induced PH was significantly related to higher creatinine levels, larger right ventricular diastolic area, TRV ≥ 2.3m/s at rest, left atrial volume index ≥ 41ml/m², and E/E’ ratio ≥ 6.3. When the multivariate analysis was performed, TRV at rest [OR 6.5 (1.3–33.6), p = 0.03], left atrial volume index [OR 6.4 (1.2–33.5), p = 0.03]; and E/E’ ratio [OR 5.6 (1.2–26.5], p = 0.03) remained independently related to exercise-induced PH.

Conclusion: Patients with sickle cell anemia and normal PP at rest may exhibit exercise-induced PH which was independently related to increased baseline PP levels, increased left atrial volumes end indirect parameters of left ventricular and diastolic pressure. The clinical relevance of these findings deserves future studies.