Prospective Multicentric Survey On Pulmonary Hypertension (PH) in Adults with Sickle Cell Disease.

Pulmonary hypertension (PH) has emerged as life threatening complication in patients with sickle cell disease. It is usually diagnosed at echocardiography by estimating systolic Pulmonary Artery Pressure (PAP) through the measurement of a velocity of tricuspid regurgitation (TRV) > 2.5 m/s. Pulmonary Hypertension diagnosed as so could affect up to 30% of patients with sickle cell disease (SCD). However, according to most guidelines, PH is rather defined by measurement of mean PAP ≥ 25 mmHg at right heart catheterism. Whether measurement of TRV ≥ 2.5 m/s at echocardiography accurately identifies patients with PH in patients with SCD, has never been evaluated.

We conducted a prospective multicentre study in 403 consecutive adult out-patients in stable clinical condition, recruited after informed consent, during 2 years (from Feb.2007 to March 2009) from 2 SCD referral centers in France (1 in Paris and 1 in Martinique). Follow -up was planned for 3 years. All patients had Doppler echocardiography, pulmonary function tests and 6 min walk test. RHC was systematically performed in case of TRV³ 2.5m/sec.

Of the 385/403 patients (SS in 379, 6 Sb⁰thalassemia) with all data availabel, sex ratio 1.5 , mean age 34±10 yrs, 96 had TRV ³ 2.5m/s (25 %) and underwent RHC. There was no PH in 72/96 with mPAp=19 ±3mmHg (false positive of echocardiography=75%). In 24 patients, m PAP was elevated (30 ± 0.4m/s). Mechanism of PH was: post-capillary PH in 13 patients (elevated pulmonary capillary wedge pressure) - hyperkinetic state in 5 patients (high cardiac output, normal pulmonary vascular resistance) - pre-capillary pulmonary arterial hypertension (PAH) in 6 patients (normal capillary wedge pressure, increased vascular resistance). Patients with a confirmed PH at RHC were significantly older (45 vs 33 yrs), had higher LDH, NT-Pro BNP, and a lower 6 min walk distance. There was no influence of long term treatment (hydroxyurea, chronic transfusion) on PH.

During follow-up (mean=11 months), 3 patients died, all in the group of patients with TRV³2.5 m/sec and confirmed PH at RHC (mPAP ³ 25 mmHg). The 24 patients having confirmed PH with RHC display similar biological and hemodynamic profile to the 18/42 with TRV³ 2.5m/sec among the 195 patients (132 SS,35SC,23S-Thalassemia b⁰or b⁺) of the Gladwin study(1), consenting to have RHC. The use of a higher cut-off value of TRV, 2.8 m/sec, decreases the false positive rate from 75% to 50%. However, 29% of patients with pulmonary hypertension (7/24) would have been undiagnosed.

PH confirmed by gold-standard technique (RHC) is relatively rare among SCD patients, with a prevalence of 24/385 (6%). PAH was present in only 6 patients (1.6%). In this population, a TRV 2.5m/s on Doppler echocardiography is inadequate to diagnose PH. The loose relationship found between TRV and pulmonary hypertension in patients with sickle cell disease does not support its use as a routine screening tool, whatever the cut-off used. Although PH on RHC was generally modest, PH seems to be an important prognostic factor. The large difference on mortality compared to previous studies will be discussed.

No relevant conflicts of interest to declare.