Pulmonary Hypertension in SS, SC and Sβ Thalassemia: Prevalence, Associated Clinical Syndromes, and Mortality.

The natural history and mechanisms associated with pulmonary hypertension (pHTN) in sickle cell disease (SCD) are incompletely characterized. We investigated the prevalence of pHTN, diagnosed by echocardiography and/or cardiac catheterization, in adults with all types of SCD, to determine whether the frequency of pHTN varied by Hgb diagnosis. We also analyzed which clinical conditions and laboratory findings were associated with pHTN. We screened 125 outpatients with Hgb SS, SC, Sβ⁰ or Sβ⁺ thalassemia who presented with symptoms including either shortness of breath, fatigue, or low or decreasing O2 saturation. PHTN was defined by tricuspid regurgitation jet velocity (TRjet) of ≥ 2.5 m/s by echo and was present in 36% (28/77) of SS & Sβ⁰ and in 25% (12/48) of SC & Sβ⁺ patients studied. Of patients with pHTN, 16 (57%) of the SS & Sβ⁰ patients had a peak TR jet >3.0 m/sec and 12 (43%) ≥2.5-<3.0m/sec, whereas 8(67%) of the SC & Sβ⁺ patients had a peak TR jet ≥3.0 m/sec (50% of these were ≥4.0) and 4 (33%) TR jet ≥2.5-<3.0m/sec. Two SS patients included in our analysis were diagnosed with pHTN by cardiac catheterization when echo failed to show pHTN. Other patients’ echos (83) were reported as either normal or abnormal but not consistent with pHTN. In SS & Sβ⁰, the mean age of patients whose echos were consistent with pHTN was significantly higher than of those without pHTN (43.3 vs. 34.4yrs, p=0.001). A similar trend was observed in SC & Sβ⁺(48.8 vs 42.6 yrs). No significant association was noted between the presence of pHTN and history of CVA, AVN, or renal failure. Patients with pHTN had higher mean systolic BP than patients without pHTN (SS & Sβ⁰126.3±19.4 vs 122.0±17.6 and SC & Sβ⁺130.7±15.0 vs 124.4±19.02 mmHg), but these differences were not statistically significant. SS & Sβ⁰ patients with pHTN had significantly lower Hgb values than patients without pHTN. Leukocyte, platelet and reticulocyte counts, creatinine, and O₂ saturation were not significantly different for patients with and without pHTN. LDH and bilirubin values were slightly higher in patients with pHTN. Most interestingly, 18/29 SS & Sβ⁰ patients with pHTN had proteinuria ≥ 1+, while only 13/46 SS & Sβ⁰ patients without pHTN had proteinuria (p<0.05). The presence of proteinuria was found to have a high positive predictive value (0.60) for the presence of pHTN in patients with SS and Sβ⁰. Proteinuria overall was rarely present in SC & Sβ⁺. During the 2 yr study period, 6/42 (14%) patients with pHTN died; deaths were limited to patients with Hgb SS and occurred at a mean of 30 months (range 5 – 53 months) after diagnosis of pHTN. The mean TR jet velocity and peak RV pressure in patients who died was 2.8m/s and 39.5, respectively. Two of 83 patients (2 %) without pHTN died during this period, suggesting that pHTN markedly increased the death rate. In conclusion, our data confirm the high prevalence of pHTN in Hgb SS, SC, and Sβ thal. Although a higher prevalence of pHTN, higher TR jet velocities, and increased mortality were seen in patients with Hgb SS or Sβ⁰, mortality was also seen in patients with relatively mild pHTN. Moreover, our data suggest that the presence of proteinuria in patients with SS or Sβ⁰ is sufficient cause to screen for pHTN by echocardiography. The mechanism by which proteinuria and pHTN are associated remains to be determined.