Pulmonary Hypertension in Thalassemia Assessed by Echocardiography: A Report From Baseline Data of the Thalassemia Clinical Research Network Longitudinal Cohort Study.

Pulmonary hypertension (PH) contributes to heart disease, the leading cause of death in thalassemia. PH in thalassemia is multifactorial, including oxidative stress, hemolysis, thrombosis, splenectomy, abnormal arginine-nitric oxide bioavailability, and iron overload. Despite the high mortality rate associated with PH, no intervention studies in thalassemia have been completed. This report summarizes the prevalence of elevated tricuspid regurgitant jet velocity (TRV) as a proxy for PH in patients clinically screened by Doppler echocardiography (echo) in the Thalassemia Clinical Research Network (TCRN).

The TCRN is an NIH-sponsored network of major thalassemia centers in the US, Canada and London, UK. This analysis is part of the Thalassemia Longitudinal Cohort (TLC), which collects longitudinal data from 428 patients at 16 centers. We report results from 303 patients (71%) who were assessed by echo at least once. Predictors considered for analysis were age, gender, splenectomy, hepatitis C, WBC, ferritin, hemoglobin, liver function, creatinine, chronic transfusion status, number of transfusions, chelation status, and hydroxyurea use. Multivariate effects of predictors significant in univariate analysis were modeled using logistic regression for elevated TRV.

Measurable TRV jet was detectable in 144/303 (48%) of patients. Average age of the cohort with a detectable TRV was 25.8 years (range 5-56 years); half were female.. 97% of the patients studied were transfusion dependent. Mean TRV was 2.3±0.4 m/s (range 0.2-3.5 m/s). An abnormal TRV ≥ 2.5 m/s was identified in 45/144 (31%) of patients screened, 18% (8/45) of whom had a TRV ≥ 3.0 m/s suggesting significant PH. Older age was strongly associated with PH (r = 0.38, p<0.0001). Mean age was significantly higher in patients with TRV≥3.0 and 2.5-2.9 m/s compared to TRV< 2.5 m/s (34.5±11 vs. 29.8±11 vs. 23.6±12 years, p = 0.003). Nine percent of children < 13 years and 7/45 (16%) of all children < 18 years screened had a TRV≥2.5 m/s. A history of splenectomy (odds ratio: 4.6; [1.8-11.9]), hepatitis C (OR: 2.5; [1.05-6.08] or high WBC (OR: 1.1; [1.02-1.2] was associated with TRV, with a p<0.05 using logistical regression modeling. After adjusting for other variables, age remained independently associated with TRV. Gender, ferritin, hemoglobin, liver function, creatinine, and hydroxyurea use were not significantly associated with TRV. A weak correlation between TRV and number of transfusions in previous 12 months was identified (r=0.17, p=0.05). No patients with an elevated TRV were on therapy for PH

Elevated TRV is noted in at least 1/3 of transfusion-dependent thalassemia patients with measurable TR jets. We observed elevated TRV in both children and adults. Less than half of patients screened by echo had a measurable TRV, suggesting that technical diligence is needed to increase the fraction of echos with a measured TRV to better identify patients at risk of PH. Age, splenectomy and history of hepatitis C are significant univariate risk factors in this population, with age remaining an independent risk factor in multiple regression analysis. Ongoing assessment in the TLC and specific prospective longitudinal studies of PH in thalassemia are needed to understand the natural history and pathophysiology in thalassemia in order to determine optimal therapy. Interventional trials for PH in thalassemia are needed.

No relevant conflicts of interest to declare.