Congenital Heart Disease
Four- and Seven-Year Outcomes of Patients With Congenital Heart Disease–Associated Pulmonary Arterial Hypertension (from the REVEAL Registry)

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Uncorrected congenital heart disease (CHD) frequently leads to pulmonary arterial hypertension (PAH), the most severe form of which is Eisenmenger syndrome (ES). We compared patients with idiopathic or heritable PAH (IPAH or HPAH; n = 1,626) against those with CHD-associated PAH (n = 353) who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL Registry). Of patients with CHD-associated PAH, 151 had ES. Compared with the IPAH or HPAH cohort, the ES cohort had greater systemic blood flow (2 ± 1 vs 3 ± 2 L/min/m2, p <0.001), lower mean right atrial pressure (10 ± 6 vs 7 ± 4 mm Hg, p <0.001), higher mean pulmonary artery pressure (53 ± 14 vs 65 ± 17 mm Hg, p <0.001), higher pulmonary vascular resistance index (22 ± 12 vs 32 ± 31 Wood units × m2, p <0.001), and lower systemic arterial oxygen saturation at rest (92 ± 11% vs 84 ± 13%, p <0.001). At 4 years from enrollment and 7 years from diagnosis, survival rate was similar between IPAH or HPAH and CHD-associated PAH cohorts. For the overall CHD-associated PAH cohort, longer 6-minute walk distance, lower mean right atrial pressure, brain natriuretic peptide level <50 pg/ml, and the presence of acute vasoreactivity were predictors of survival at 4 years from enrollment; younger age and lower mean right atrial pressure were predictors of survival at 7 years from diagnosis. In conclusion, these observations support predicted physiologic differences (e.g., hemodynamics) between patients with IPAH or HPAH and patients with CHD-associated PAH, with or without a systemic-pulmonary shunt. These differences, however, did not translate into significantly improved 4- and 7-year survival rates in patients with ES versus IPAH or HPAH and CHD-associated PAH.

Section snippets

Methods

The design and baseline characteristics of the patients enrolled in the REVEAL Registry have been previously described.7, 8 REVEAL, a longitudinal registry involving 55 pulmonary hypertension centers in the United States (university affiliated and community hospitals), was designed to provide current information about the demographics, course, and management of newly and previously diagnosed patients with World Health Organization group 1 PAH. The data download for this analysis occurred on

Results

From March 30, 2006 to December 8, 2009, 3,515 patients with newly and previously diagnosed PAH were enrolled in REVEAL. The study cohort consisted of 1,979 patients (Figure 1), of whom 1,626 had IPAH (n = 1,530) or HPAH (n = 96), and 353 had CHD-associated PAH (hereafter referred to as CHD). Within the CHD group, most (n = 248) were unrepaired or partially repaired, including 151 patients classified as having ES, 91 patients classified as not having ES, and 6 patients for whom ES

Discussion

This analysis of REVEAL showed that despite hemodynamic differences between the IPAH or HPAH, repaired CHD, and ES cohorts, survival rate at 4 years from enrollment was similar across groups and survival rate at 7 years from diagnosis was similar between the IPAH or HPAH and ES cohorts. These findings appear to be incongruous with previous studies showing both slower PAH disease progression18 and significantly better survival rate5, 19 in patients with ES than in patients with IPAH or HPAH. It

Acknowledgment

Assistance in manuscript development was provided by Anna Lau, PhD, of Percolation Communications LLC. Ginny Lai of ICON Late Phase & Outcomes Research provided statistical programming support.

The authors are saddened to report the passing of Robyn J. Barst, MD, in April 2013. She was an esteemed physician, investigator, and colleague, and a distinguished leader in the field of pediatric pulmonary hypertension. Her contributions to the field are invaluable.

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    • Cited by (0)

    Institution where work was performed: 55 participating sites across the United States.

    Funding and support for the REVEAL Registry was provided by Cotherix, Inc. and its affiliate Actelion Pharmaceuticals US, Inc. Funding for preparation of this manuscript was provided by Actelion Pharmaceuticals US, Inc., South San Francisco, California.

    See page 154 for disclosure information.

    †

    Deceased.

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