Eisenmenger syndrome and atrial septal defect: nature or nurture?

BACKGROUND: It has long been debated whether patients with atrial septal defect (ASD) Eisenmenger syndrome have idiopathic pulmonary arterial hypertension with an incidental ASD or severe pulmonary hypertension on the basis of their ASD shunt magnitude alone. HYPOTHESIS: It was hypothesized that if ASD Eisenmenger patients had idiopathic pulmonary arterial hypertension with an incidental ASD, a mutation in the bone morphogenetic protein receptor-2 (BMPR2) would be found in some of these patients. PATIENTS AND METHODS: All adult patients with ASD Eisenmenger syndrome were identified from the databases of two adult congenital cardiac units, and were matched to a control group with similar types of ASDs and no pulmonary hypertension. Gene coding for BMPR2 was examined for mutation using denaturing high-performance liquid chromatography of the entire coding sequence.
RESULTS: Eighteen adult patients with ASD Eisenmenger syndrome and 18 control patients were identified. ASD Eisenmenger patients had significantly larger ASDs than the control patients (3.7+/-1.2 cm versus 1.9+/-0.7 cm, P<0.01). A mutation in BMPR2 was not detected in either group.
CONCLUSION: ASD Eisenmenger syndrome may occur without BMPR2 mutation. Whether shunt magnitude alone or in combination with yet another genetic mutation is responsible for the development of pulmonary hypertension in these patients remains to be determined.