Impact of sildenafil on echocardiographic indices of myocardial performance after the fontan operation

David J. Goldberg; Benjamin French; Anita L. Szwast; Michael G. McBride; Bradley S. Marino; Nicole Mirarchi; Brian D. Hanna; Gil Wernovsky; Stephen M. Paridon; Jack Rychik

doi:10.1007/s00246-012-0196-9

Impact of sildenafil on echocardiographic indices of myocardial performance after the fontan operation

David J. Goldberg^*, Benjamin French, Anita L. Szwast, Michael G. McBride, Bradley S. Marino, Nicole Mirarchi, Brian D. Hanna, Gil Wernovsky, Stephen M. Paridon, Jack Rychik

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

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.

Original language	English (US)
Pages (from-to)	689-696
Number of pages	8
Journal	Pediatric cardiology
Volume	33
Issue number	5
DOIs	https://doi.org/10.1007/s00246-012-0196-9
State	Published - Jun 2012

Funding

The authors thank Erin Davis, Anysia Fedec, the staff of the Echocardiography Laboratory, and the staff of the Investigational Pharmacy at The Children’s Hospital of Philadelphia for their assistance and contributions to this work. This study was supported by grants from the The Mark H. and Blanche M. Harrington Family Foundation and from Big Hearts to Little Hearts. D. J. G. received support from NIH T32 Grant no. HL07915.

Keywords

Echocardiography
Fontan procedure
Physiology
Sildenafil
Trials

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Pediatrics, Perinatology, and Child Health

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@article{9c5a6f9047cc4381a70fed412e927436,

title = "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.",

keywords = "Echocardiography, Fontan procedure, Physiology, Sildenafil, Trials",

author = "Goldberg, {David J.} and Benjamin French and Szwast, {Anita L.} and McBride, {Michael G.} and Marino, {Bradley S.} and Nicole Mirarchi and Hanna, {Brian D.} and Gil Wernovsky and Paridon, {Stephen M.} and Jack Rychik",

note = "Funding Information: The authors thank Erin Davis, Anysia Fedec, the staff of the Echocardiography Laboratory, and the staff of the Investigational Pharmacy at The Children{\textquoteright}s Hospital of Philadelphia for their assistance and contributions to this work. This study was supported by grants from the The Mark H. and Blanche M. Harrington Family Foundation and from Big Hearts to Little Hearts. D. J. G. received support from NIH T32 Grant no. HL07915.",

year = "2012",

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doi = "10.1007/s00246-012-0196-9",

language = "English (US)",

volume = "33",

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AU - Goldberg, David J.

AU - French, Benjamin

AU - Szwast, Anita L.

AU - McBride, Michael G.

AU - Marino, Bradley S.

AU - Mirarchi, Nicole

AU - Hanna, Brian D.

AU - Wernovsky, Gil

AU - Paridon, Stephen M.

AU - Rychik, Jack

N1 - Funding Information: The authors thank Erin Davis, Anysia Fedec, the staff of the Echocardiography Laboratory, and the staff of the Investigational Pharmacy at The Children’s Hospital of Philadelphia for their assistance and contributions to this work. This study was supported by grants from the The Mark H. and Blanche M. Harrington Family Foundation and from Big Hearts to Little Hearts. D. J. G. received support from NIH T32 Grant no. HL07915.

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

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KW - Fontan procedure

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ER -

Impact of sildenafil on echocardiographic indices of myocardial performance after the fontan operation

Abstract

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Keywords

ASJC Scopus subject areas

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