Title: Improved Survival Among Patients With Eisenmenger Syndrome Receiving Advanced Therapy for Pulmonary Arterial Hypertension
Topic: Congenital Heart Disease
Date Posted: 3/17/2010
Author(s): Dimopoulos K, Inuzuka R, Goletto S, et al.
Citation: Circulation 2010;121:20-25.
Clinical Trial: No
Study Question: What is the effect of advanced therapy (AT) (pulmonary vasodilators) on survival in patients with Eisenmenger syndrome?
Methods: A retrospective review was performed over a 10-year period at a single center. Survival rates were compared between patients on and off AT with use of a modified version of the Cox model, treating AT as a time-varying covariate.
Results: A total of 229 patients, mean age 34.5 ± 12.6 years, were studied. The majority had complex anatomy (atrioventricular septal defects, univentricular physiology, transposition of the great arteries, aortopulmonary window, common arterial trunk, and operated lesions), with 29.7% of patients having Down syndrome. Mean resting oxygen saturation was 84.3%. Sixty-eight patients (29.7%) were on AT at the beginning of the study period or started on AT at some point during the study period. The majority of patients on AT were on bosentan (73.5%), whereas some were on sildenafil (25%) and epoprostenol (1.5%). During a median follow-up of 4.0 years, 52 patients died, 2 of them while on AT. Patients on AT were at a significantly lower risk of death, both unadjusted and adjusted for baseline clinical differences by propensity score regression adjustment (C-statistic, 0.8; hazard ratio, 0.16; 95% confidence interval, 0.04-0.71; p = 0.015) and propensity score matching (hazard ratio, 0.10; 95% confidence interval, 0.01-0.78; p = 0.028).
Conclusions: Pulmonary vasodilator therapy for pulmonary arterial hypertension in adults with Eisenmenger syndrome was associated with a lower risk of death.
Perspective: This important study is the first large-scale study to demonstrate survival benefit from pulmonary vasodilators in adults with Eisenmenger physiology. Historically, clinicians have favored a minimally interventional approach towards patients with Eisenmenger physiology with a goal of not upsetting the fragile homeostasis often seen in this patient population. The randomized and controlled BREATHE-5 study of bosentan demonstrated improvement in exercise capacity and pulmonary hemodynamics without compromising systemic oxygen saturation (Circulation 2006;114:1807-10). There was no demonstrated mortality benefit over a short study period, and patients generally did not have complex disease. In the current study, a majority of patients had complex disease, and almost one-third had Down syndrome, which is reflective of the population seen at most centers. These results suggest that clinicians should rethink the minimalist strategy often employed in adults with Eisenmenger physiology. Timothy B. Cotts, M.D., F.A.C.C.
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