Genetic Pulmonary Hypertension Combined With Biventricular Heart Failure: Role of AQP1 Gene Mutation.

BACKGROUND

Aquaporin-1 (AQP1) mutations are a rare cause of heritable pulmonary artery hypertension. The clinical manifestation remains poorly defined, and coexisting left ventricular dysfunction has not been reported.

CASE SUMMARY: A 34-year-old man presented with severe pulmonary arterial hypertension and biventricular dysfunction. Genetic testing revealed a heterozygous AQP1 mutation, c.551T >C (p.Ile184Thr), not previously reported; family screening confirmed the same variant in his mother and daughter. After 6 months of guideline-directed medical therapy and endothelin receptor antagonist therapy, pulmonary artery pressure decreased significantly, and functional capacity improved.

DISCUSSION: Biventricular impairment raises 2 hypotheses: septal dyskinesia secondary to right ventricular overload, or myocardial impairment because of altered AQP1 channel function. The favorable response suggests targeted pulmonary vasodilator therapy may benefit in this rare genetic subset.

TAKE-HOME MESSAGE: AQP1 mutations should be considered in genetic workup of pulmonary arterial hypertension and may coexist with left ventricular dysfunction responsive to endothelin receptor antagonist therapy.