Results of a study published in Blood offer greater insight into mortality rates of patients with beta thalassemia and confirmed pulmonary arterial hypertension (PAH). In addition to characterizing mortality outcomes, the study also suggests that improving systolic pulmonary artery pressure (sPAP) with pharmacologic agents may reduce mortality in these patients.
The findings “further our understanding of the detrimental impact of PAH, irrespective of the underlying patient profile,” said corresponding author Gian Luca Forni, MD, of Galliera Hospital in Genoa, Italy.
Dr. Forni and colleagues sought to identify long-term mortality outcomes in a subgroup of patients with PAH that was confirmed with right heart catheterization (RHC) in a previous multicenter study. Patients in the multicenter study were initially recruited between January 2012 and January 2013. They were 18 years of age or older with beta thalassemia major or intermedia and without chronic restrictive lung disease or a left ventricular ejection fraction of 50% or less (n=1,309).
A total of 27 patients had confirmed PAH with a pulmonary capillary wedge pressure of 15 mm Hg or less (precapillary PH). The authors followed 24 of these patients until March 2021, death, or loss to follow-up, whichever came first. The median age of the patients was 46.5 years, and the median follow-up period was four years.
Thirteen patients died during the observation period, which corresponded to an unadjusted all-cause mortality rate of 54.2% (95% CI 32.9-74.5). Hepatic disease or sepsis were the cause of death in three patients, while 10 patients died as a result of PAH. Overall, the researchers reported a crude PAH-related mortality rate of 41.7% (95% CI 22.1-63.4). Causes of death included right-sided heart failure (n=9) and pulmonary embolism (n=1).
The median survival period was nine years. Cumulative PAH-related mortality-free survival estimates were 78% at one year, 65% at two years, and 60% at five years.
In an analysis that compared patients who died from PAH versus those who did not, the researchers found no statically significant differences in demographics, thalassemia diagnosis (p=1.0), splenectomy status (p=0.49), baseline hemoglobin (p=0.52), serum ferritin (p=0.08), or New York Heart Association class (p=0.67).
Additionally, echocardiography and RHC values at baseline were comparable between patients who died from PAH versus those who did not. However, patients who died because of PAH had numerically lower sPAP and cardiac index and higher pulmonary vascular resistance and vasoreactivity.
A significant difference was observed between patients who died from PAH and those who did not in terms of the median absolute change in sPAP (+6.5 vs. -21.6 mm Hg, respectively; p=0.024). The relative change in sPAP on receiver operating characteristic curve analysis was considered a strong predictor of PAH-related mortality (p=0.011).
Among the 21 patients who received PAH-related treatment, 58.3% (n=14) received monotherapy and 29.2% (n=7) received double therapy. Treatments included bosentan, ambrisentan, sildenafil, tadalafil, macitentan, riociguat, and other angiotensin-converting enzyme inhibitors, calcium channel and beta-blockers, and anticoagulants. The unadjusted PAH-related mortality rate was 38.1% in patients who received any PAH-related treatment.
Additionally, the unadjusted PAH-related mortality rates were 66.7% in patients who received no therapy, 42.9% in patients who received single-agent therapy, and 28.6% in patients who received two agents (p=0.529). The cumulative five-year PAH-related mortality-free survival estimates were 33%, 52%, and 86%, respectively (p=0.511).
Compared to patients with no PAH-related therapy, patients with single and double agent therapy had a hazard ratio for death of 0.710 (95% CI 0.143-3.52) and 0.352 (95% CI 0.049-2.514), respectively. The median relative change in sPAP on echocardiography was higher in patients with double versus single agent versus no PAH-related therapy, but this did not reach statistical significance (-54.5% vs. 1.5% vs. -8.7%, p=0.371).
According to Dr. Forni, there are significant research needs to help close knowledge gaps regarding patients with beta thalassemia and confirmed PAH. “Randomized trials evaluating agents targeting PAH in this group of patients are needed,” he said, “and disease-specific guidelines to prevent and care for this complication are also merited.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Pinto VM, Musallam KM, Derchi GE, et al. Mortality in β-thalassemia patients with confirmed pulmonary arterial hypertension on right heart catheterization [published online ahead of print, 2022 Jan 5]. Blood. doi: 10.1182/blood.2021014862.
