Exercise Capacity and Pulmonary Function in Sickle Cell Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is increasingly recognised as a complication of sickle cell disease (SCD), with a prevalence of approximately 30%. In SCD, a tricuspid regurgitant jet velocity (TRV; determined by cardiac ultrasound) of 2.5 m/s or higher is used as a non-invasive marker of PAH and is associated with a poor prognosis. Since PAH in SCD is usually mild, it remains unclear whether PAH is directly responsible for the early death of these patients. Exercise capacity is closely related to survival in heart failure and other chronic cardiopulmonary diseases. We hypothesized that if PAH in SCD determines survival, it should be related to exercise capacity. The aim of this study was to determine whether exercise capacity is reduced in SCD patients with an increased TRV. In addition, it was determined whether exercise capacity is related to pulmonary function in these patients. Cardiac ultrasound, pulmonary function testing and a symptom-limited maximal cardiopulmonary exercise tests(CPET) using cycle ergometry were performed in 42 consecutive patients with SCD. PAH was present in 9/42 (21%) of the patients. Exercise capacity was decreased in all patients, with a trend to a lower peak oxygen uptake (VO2peak) and oxygen uptake at the anaerobic threshold (VO2peak/AT) in patients with PAH compared to patients without PAH (74±18% and 57±18% versus 63±14% and 46±10%, respectively, p=0.16 and p=0.095). After matching for blood hemoglobin content, differences in exercise capacity disappeared. Pulmonary function was also impaired in both groups, with much larger differences between PAH and non-PAH patients: vital capacity (%predicted) 72±13% vs 85±15% and total lung capacity 70±11% vs. 81±11% (p=0.025 and p=0.020). No differences in FEV1 or membrane diffusion capacity were demonstrated. Multiple regression analysis, with the use of VO2peak as dependent variable and age, SCD phenotype, hemoglobin, spirometric parametres and TRV identified only vital capacity and hemoglobin as a significant independent correlates of VO2peak and not TRV. In conclusion, PAH in SCD is not related to exercise capacity, which could mean that it has no direct effect on mortality. SCD is associated with a restrictive pulmonary function impairment, especially in the group of patients with PAH. Interestingly, low VO2peak in SCD appears to be determined by the severity of the anemia instead of the prevalence of PAH.