Abstract 11838: Isosorbide Dinitrate Effect May Improve Exercise Tolerance, Venous Pressure and Liver Stiffness in Patients With Fontan Circulation (The NEET Clinical Trial)

Abstract

Introduction: After the Fontan operation, decreased venous capacitance (venoconstriction) and elevated central venous pressure may result in worse clinical outcomes, worse exercise capacity, and increased liver stiffness. This pilot study evaluated the acute effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. Methods: In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after four weeks of treatment with ISDN. Cardiopulmonary exercise testing was performed to assess exercise tolerance, with a primary outcome of peak oxygen consumption (peak VO 2 ). The secondary outcome included VO 2 at the anaerobic threshold (AT VO 2 ), PVP at rest and peak exercise and liver stiffness measured by ultrasound prior to the exercise test. Repeated measure t-test was used to test for differences in outcomes in response to ISDN. Results: The mean age was 23.5 ± 9.2 years (range 11.2-30.6 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO 2 from baseline (1401±428 to 1428±436 ml/min, p=0.128), but there was an improvement in AT VO 2 (1087 ± 313 to 1115 ±302 mL/min, p= 0.03). Treatment with ISDN was associated with lower peak exercise PVP (22.5 ±4.5 to 20.6 ± 2.99 mmHg, p=0.015) without a notable difference in the resting PVP (p=0.357). There was a trend towards lower liver stiffness with ISDN (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p=0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Conclusions: Treatment with ISDN for 4 weeks is well-tolerated except for headache and appears safe in patients with a Fontan circulation. ISDN therapy was associated with improvements in certain exercise and hemodynamic parameters as well as a trend towards lowering liver stiffness. Larger studies will be necessary to validate these physiologic findings and further evaluate the effects of nitrates on meaningful clinical outcomes.