Impact of Sildenafil on Echocardiographic Indices of Myocardial Performance After the Fontan Operation

Abstract

The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI; −0.051; 95% CI −0.095, −0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm × bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI × HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.

Sildenafil Improves Exercise Hemodynamics in Fontan Patients

“…Extending this experience, Goldberg et al 9,10 demonstrated an improvement in ventilatory efficiency and ventricular performance after a 6-week period of sildenafil treatment.…”

“…3,[8][9][10] This postsildenafil increase in CI may be attributed to a relative increase in HR, an unchanged EDVi, and a decrease in both TPRi and ESVi when compared with the presildenafil setting. TPRi was observed to be lower throughout exercise in the postsildenafil setting, but the most significant difference was observed during high-intensity exercise where TPRi remained unchanged, in contrast to the increase observed during exercise before sildenafil.…”

“…34 Khambadkone et al 3 showed that pulmonary vascular resistance was elevated late after the Fontan operation and may fall in response to inhaled NO. Giardini et al 8 showed an improvement in peak oxygen consumption after a single oral dose of sildenafil, whereas Goldberg et al 9,10 observed an improvement in ventilatory efficiency and ventricular performance after a 6-week period of sildenafil therapy. Rhodes et al 35 noted a similar beneficial effect of inhaled iloprost on exercise capacity.…”

Hemodynamic performance of the Fontan circulation compared with a normal biventricular circulation: a computational model study

“…This highlights the importance of active hemodynamic management in the care of long-term survivors. Although some studies have reported the beneficial roles of some medications [e.g., administration of sildenafil (30), amrinone (78), or sodium nitroprusside (93)] in increasing resting CO or improving ventricular performance, to date, evidence supporting the longterm effectiveness of certain interventions in systemically improving hemodynamic conditions remains absent. The present theoretical study demonstrates that the mechanisms underlying the regulation of CO and central venous pressure differ significantly between the Fontan circulation and the biventricular circulation, which implies that some conventional medications for treating patients with biventricular physiology might not be applicable to Fontan patients.…”

Chronic Heart Failure in Congenital Heart Disease

“…A single dose improved peak V ⋅ o 2 during exercise with a measurable increase in both pulmonary and systemic blood flow at peak exercise. 211,212 Others series showed a favorable impact on the Doppler-derived myocardial performance index 213 and systolic arterial and ventricular elastance. 214 With longer therapy, a double-blind, placebocontrolled crossover trial showed an improvement in the ventilatory efficiency slope during cardiopulmonary exercise testing, although other parameters were not improved.…”