Pulmonary artery hypertension (PAH) is a serious complication associated with considerable morbidity and mortality. The prevalence of PAH in patients with β-thalassemia is reported to be high, and is attributed to several pathophysiologic mechanisms including hemolysis, hypercoagulability, and iron overload. However, most available studies relied only on echocardiographic estimation of the prevalence of PAH. Recently, a study in patients with sickle cell disease established that echocardiographic evaluation alone has a low positive predictive value for PAH (Parent F, et al. NEJM 2011). The aim of this study was to establish the true prevalence of PAH in a large group of patients with β-thalassemia major (TM) and intermedia (TI) using right heart catheterization.
This was a multicenter observational study of adult TM and TI patients attending Italian centers participating in the Webthal® project. The study lasted 12 months. Patients were followed, treated, and examined according to the Italian Society for the Study of Hemoglobinopathies (SITE), Thalassemia International Federation (TIF), and Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC) guidelines. Patients were initially screened with transthoracic echocardiography and divided into three groups based on the findings: Group A: pulmonary artery pressure (PAP) <36 mm Hg or a tricuspid regurgitant jet velocity (TRV) <3.0 m/s; Group B: PAP >40 mm Hg or TRV >3.2 m/s; and Group C: PAP 36–40 mm Hg or TRV 3.0–3.2 m/s. Patients in Group B further underwent right heart catheterization to confirm the diagnosis of PAH.
A total of 1309 patients were recruited in this study (mean age 36 ± 9 year, 85.1% males) including 977 TM (mean age 34 ± 7, 83.3% males), and 332 TI (mean age 43 ± 1236, 90.8% males) patients. After initial screening, the prevalence of the three groups was as follows: All patients (Group A: n=1234 [94.2%], Group B: 47 [3.6%], Group C: 28 [2.1%]); TM patients (Group A: n=946 [96.8%], Group B: 16 [1.6%], Group C: 15 [1.5%]); TI patients (Group A: n=288 [86.7%], Group B: 31 [9.3%], Group C: 13 [3.9%]). The echocardiographic PAH prevalence estimate was 5.7% (3.2% in TM and 13.3% in TI patients) if Groups B and C are considered to have PAH; and 3.6% (1.6% in TM and 9.3% in TI patients) if only Group B is considered to have PAH. Out of the 47 patients in Group B, 33 (13 TM and 20 TI) underwent right heart catheterization (7 patients declined the procedure, 1 died, 3 were excluded because of low hemoglobin, 2 were excluded due to chronic cardiopulmonary problems, and 1 was excluded due to an erythropoietic extramedullary mass). Out of the 33 patients, 31 (93.9%, representing positive predictive value for the echocardiographic TRV >3.2 m/s threshold) had a confirmed PAH diagnosis on right heart catheterization (12 TM and 19 TI). Accordingly, the prevalence of PAH in the study sample was 2.4% (1.2% in TM and 5.7% in TI).
The true prevalence of PAH using right heart catheterization in patients with β-thalassemia is 2.4%, with a higher prevalence noted in TI than TM patients (∼5-fold).
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.