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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.www.clinicaltrials.gov ; Clinicaltrials.gov Identifier: NCT01815502.

SUBMITTER: Butts RJ

PROVIDER: S-EPMC4833409 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Butts Ryan J RJ Chowdhury Shahryar M SM Baker George H GH Bandisode Varsha V Savage Andrew J AJ Atz Andrew M AM

Pediatric cardiology 20150926 1

<h4>Unlabelled</h4>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 t ...[more]

PMID: 26409473

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Project description:ObjectivePhysical activity at high altitude is expected to pose risks for patients with Fontan circulation and to impair systemic ventricular function. This study aims to determine the effect of high-altitude hypoxia on ventricular function in Fontan patients at rest and after exercise. We hypothesize that systemic ventricular function deteriorates under hypoxic conditions in Fontan patients.MethodsIn this prospective study, 21 Fontan patients (NYHA class I-II) and 21 age-, gender- and body mass index-matched healthy controls were enrolled (median age 17.9 and 16.9 years). Transthoracic echocardiography was performed at rest, after peak (PE) and after continuous exercise (CE) in normoxia and hypoxia at simulated altitude (2,500 m above sea level). The effect of hypoxia on echocardiographic parameters was quantified by linear mixed-effects models and the difference between normoxia and hypoxia (Δ= hypoxia-normoxia).ResultsAt rest, cardiac output (CO) estimated by outflow tract velocity time integral × heart rate and annular plane systolic excursion (APSE) were lower in hypoxia compared to normoxia in Fontan patients (CO: Δ = -12.0%, n.s.; APSE: Δ = -9.6%, p < 0.001), an increase was observed in controls (CO: Δ = 8.5%, n.s.; APSE: Δ = 2.5%, n.s.). Other parameters of systolic and diastolic function did not show relevant changes. After exercise under hypoxic conditions, Fontan patients did not show relevant deterioration of systolic function compared to normoxia. Late, active diastolic filling reflected by A-wave velocity remained unchanged in Fontan patients, but increased in controls. Under hypoxic conditions, CO and workload were higher after CE than PE in Fontan patients (CO: PE Δ = 1,530 vs. CE 1630), whereas controls showed higher work load and CO estimates after PE than CE as expected (CO: PE Δ = 2,302 vs. CE 2149).ConclusionFontan patients clinically tolerated short-term altitude exposure up to two hours and exercise and showed no consistent deterioration of systolic systemic ventricular function, but parameters of myocardial contractility, heart rate and cardiac output did not increase as observed in controls. This is likely to be multifactorial and may include intrinsic cardiac dysfunction as well as preload inadequacy and the lack of augmented atrial contraction. CE may be better tolerated than PE.

Dataset Information

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

Publications

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

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