Pilot Study of Inhaled Nitric Oxide to Treat Pulmonary Insufficiency in Congenital Heart Disease

Pulmonic valve insufficiency (PI) is a well-defined problem after primary surgical repair of Tetralogy of Fallot (TOF). Though well-tolerated for years, long-term PI can lead to structural changes in the right ventricle, the sequelae of which include right heart failure, arrhythmia, and sudden cardiac death. The only current treatment for severe symptomatic PI is pulmonic valve replacement. We hypothesize that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, can acutely decrease PI as assessed by cardiac magnetic resonance imaging (CMR). Methods: 22 consecutive patients with PI in the setting of corrected TOF or post pulmonic valve balloon valvuloplasty will undergo a clinically indicated CMR. Nitric oxide gas will be delivered via facemask through a specialized delivery device at 40ppm. After 5 minutes, flow velocity mapping and gradient echo sequences will be repeated to assess pulmonary regurgitant fraction, right ventricular volumes, and ejection fraction. Nitric oxide will be discontinued after acquisition of the last picture. Wilcoxon rank-sum for paired data will be used to assess effect of intervention. Significance: If decreasing pulmonary vascular resistance decreases PI, medical therapy with long-acting pulmonary vasodilators may be an attractive therapeutic option with the goal of delaying or even obviating pulmonic valve replacement.

Inclusion Criteria: Known pulmonary insufficiency status Previous Tetralogy of Fallot repair or balloon valvuloplasty/surgical valvotomy for pulmonary stenosis Clinically indicated cardiac magnetic resonance imaging study Exclusion Criteria: Enrollment in another clinical trial Age less then 18 years Inability to provide informed consent Institutionalized individual Pregnant or lactating Serious claustrophobia Pacemaker/ICD Aneurysm clips Internal hardware Severe obesity (>350lbs) Residual ventricular septal defect History of methemoglobinemia History of blood dyscrasias Acute pulmonary infection Pulmonary edema Hypersensitivity to nitric oxide or any of its components Left ventricle dysfunction (EF<40%) Concurrent use of nitroglycerin or prilocaine

Hart SA, Devendra GP, Kim YY, Flamm SD, Kalahasti V, Arruda J, Walker E, Boonyasirinant T, Bolen M, Setser R, Krasuski RA. PINOT NOIR: pulmonic insufficiency improvement with nitric oxide inhalational response. J Cardiovasc Magn Reson. 2013 Sep 4;15(1):75. doi: 10.1186/1532-429X-15-75.