Effect of Sildenafil on Pressure-Volume Loop Measures of Ventricular Function in Fontan Patients

Abstract

Sildenafil has been reported to improve exercise capacity in Fontan patients, but the physiologic mechanisms behind these findings are not completely understood. The objective of this study was to study the acute effect of sildenafil on pressure-volume loop (PVL) measures of ventricular function in Fontan patients. Patients after Fontan operation who were presenting for a clinically indicated catheterization were enrolled. Patients were randomized in a double-blinded fashion to receive placebo (n = 9) or sildenafil (n = 10) 30-90 min prior to catheterization. PVLs were recorded using microconductance catheters at baseline and after infusion of dobutamine (10 mcg/kg/min). The primary outcome was change in ventriculoarterial (VA) coupling. For the entire cohort, VA coupling trended toward improvement with dobutamine (1.4 ± 0.4 to 1.8 ± 0.9, p = 0.07). End-systolic elastance showed improvement (2.6 ± 0.9 to 3.8 ± 1.4 mmHg m(2)/ml, p < 0.01) with dobutamine infusion. The cohorts had similar VA coupling at baseline (p = 0.32), but the sildenafil cohort trended toward having less of an improvement in VA coupling with dobutamine stress (p = 0.06). There were no differences between PVL measures of systolic or diastolic function between treatment groups, both at baseline and after dobutamine infusion. Patients with Fontan circulation had improved contractility and trended toward improvement in VA coupling with dobutamine stress. Acute sildenafil administration was not associated with improved PVL measurements of ventricular function in this population. These results suggest that clinical improvements seen with administration of sildenafil in Fontan patients are not associated with an acute improvement in ventricular function.

Clinical trial registration: www.clinicaltrials.gov ; Clinicaltrials.gov Identifier: NCT01815502.

Keywords: Fontan; Pressure–volume loop; Sildenafil; Single-ventricle heart disease.

Figures

Fig. 1

Change in heart rate from baseline (left side of graph) to post-dobutamine heart rate (right side of graph). Each line represents an individual patient. Median heart rate increased from 80 to 120 beats/min

Fig. 2

Boxplot of end-systolic elastance (Ees), end-arterial elastance (EA) and VA coupling (Ees/EA). White boxplots represent baseline pressure–volume loop measurements; gray boxplots represent measurements after dobutamine stress. There was an improvement in Ees with dobutamine (p < 0.01), a trend toward increasing EA (p = 0.07) and trend toward improving VA coupling (p = 0.07)

Fig. 3

Representative pressure–volume loops acquired from one study patient. Pressure–volume loop with dashed line displays baseline recordings. Solid line pressure–volume loop displays recording with dobutamine stress. Lines represent respective calculated end-systolic elastance lines. Steeper slope of dobutamine endsystolic elastance demonstrates improved contractility