Clinical phenotypes and outcomes of precapillary pulmonary hypertension of sickle cell disease

Abstract

RationalePrecapillary pulmonary hypertension (PH) is a devastating complication of sickle cell disease (SCD). Little is known about the influence of the SCD genotype on PH characteristics.ObjectivesTo describe clinical phenotypes and outcomes of precapillary PH due to SCD according to disease genotype.MethodsA nationwide multicentre retrospective study including all patients with SCD-related precapillary PH from the French PH Registry was conducted. Clinical characteristics and outcomes according to SCD genotype were analysed.Results58 consecutive SCD patients with precapillary PH were identified, of whom 41 had homozygous for haemoglobin S (SS) SCD, three had S-β0 thalassaemia (S-β0 thal) and 14 had haemoglobin SC disease (SC). Compared to SC patients, SS/S-β0 thal patients were characterised by lower 6-min walk distance (p=0.01) and lower pulmonary vascular resistance (p=0.04). Mismatched segmental perfusion defects on lung scintigraphy were detected in 85% of SC patients and 9% of SS/S-β0 thal patients, respectively, and 50% of SS/S-β0 thal patients had heterogeneous lung perfusion without segmental defects. After PH diagnosis, 31 patients (53%) received medical therapies approved for pulmonary arterial hypertension, and chronic red blood cell exchange was initiated in 23 patients (40%). Four patients were managed for chronic thromboembolic PH by pulmonary endarterectomy (n=1) or balloon pulmonary angioplasty (n=3). Overall survival was 91%, 80% and 60% at 1, 3 and 5 years, respectively, without influence of genotype on prognosis.ConclusionsPatients with precapillary PH related to SCD have a poor prognosis. Thrombotic lesions appear as a major component of PH related to SCD, more frequently in SC patients.

Long‐term tolerability of phosphodiesterase‐5 inhibitors in pulmonary hypertension of sickle cell disease

“…The link between chronic thromboembolic disease and PH in SCD remains unclear. A recently published case series of 58 patients with sickle cell disease and precapillary PH found mismatched segmental perfusion defects on lung scintigraphy in 85% of HbSC patients and 9% of HbSS/S‐β0 thal patients, respectively 23 . To further explore this observation, we performed a subgroup analysis of subjects diagnosed with CTEPH and following PDE5‐I therapy, found no significant difference in mortality ( P = .28), or NYHA class ( P = .36) compared with subjects without evidence of CTEPH.…”

Clinical and physiological characteristics of, medically treated, chronic thromboembolic pulmonary hypertension patients in Saudi Arabia: A single center experience

“…[ 23 24 25 ] Both pre and postcapillary PH are seen in PH-SCD, however, the precapillary component has been reported to be slightly more prevalent in previous studies[ 26 27 ] and is associated with poor prognosis. [ 26 28 ] Chronic thromboembolism and intravascular hemolysis leading to nitric oxide depletion and endothelial dysfunction are major contributors to precapillary PH-SCD. A recent study has shown a high prevalence of mismatched segmental perfusion defects in VQ scintigraphy and advocates the use of VQ scan for CTEPH screening in this population.…”

Pulmonary Complications of Sickle Cell Disease: A Narrative Clinical Review

“…There are five different groups of PH: 1) pulmonary arterial hypertension, 2) PH due to left heart disease, 3) PH due to chronic lung disease/hypoxia, 4) PH due to chronic pulmonary thromboembolisms, and 5) PH due to unclear multifactorial mechanisms. PH related to SCD is currently in group 5 as some patients show hemodynamic changes consistent with group 1, while others have features of group 2 or group 4 PH [50,51].…”