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Carvedilol Does Not Improve Exercise Performance in Fontan Patients: Results of a Crossover Trial

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Abstract

Increased circulating catecholamines are associated with worse exercise performance in adult heart failure patients. Patients with Fontan physiology have increased circulating catecholamines and theoretically could benefit from beta blockade. We hypothesized that carvedilol would improve exercise performance in Fontan patients. A double-blind, placebo-controlled, crossover trial of carvedilol was performed. Single ventricle patients between the ages of 10 and 35 years with a previous Fontan operation who were able to complete a maximal exercise test (respiratory exchange ratio > 1.0) were included. Two 12-week treatment arms were separated by a 6-week washout period. Exercise testing was performed at beginning and end of each treatment arm. Primary endpoint was improvement in peak oxygen consumption/kg (pVO2) from baseline. Of the 26 subjects enrolled, 23 completed the study. Four subjects did not reach goal maximum carvedilol dose, vs. 1 for placebo (p = 0.14). The mean change in pVO2 between treatments was not different (carvedilol = − 2.1 mL/kg/min v. placebo = − 1.42, p = 0.28). Carvedilol therapy decreased peak heart rate by 4.2 ± 20.2 bpm, (p < 0.01) leading to an increase in peak oxygen pulse (p < 0.01). Serum N-terminal-proBNP increased with carvedilol therapy (mean change of + 23.77 pg/mL) compared to placebo (mean change of − 5.37 pg/mL, p = 0.03). There were no serious adverse events related to study drug. Carvedilol was not associated with improved exercise performance and was associated with mildly increased N-terminal-proBNP. This study does not support the routine administration of carvedilol to healthy Fontan patients.

Clinical Trials Registration ClinicalTrials.gov Identifier: NCT02946892. Registered October 27, 2016. Retrospectively Registered. https://clinicaltrials.gov/ct2/show/NCT02946892

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to recognize Dr. Souad Messahel for her contribution to the study. The study was funded by an American Heart Association mentored clinical research grants.

Funding

The study was funded by an AHA mentored clinical research grants (PI: RB, Award # 16MCPRP31350009).

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Authors and Affiliations

  1. Division of Cardiology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA

    Ryan Butts, Nathanya BaezHernandez, David Sutcliffe & Lynn Mahony

  2. Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA

    Andrew M. Atz

  3. Division of Biostatistics, Department of Population and Data Sciences, University of Texas Southwestern, Dallas, TX, USA

    Joan Reisch

  4. Children’s Medical Center of Dallas, 1935 Medical District Drive, B3.09, Dallas, TX, 75235, USA

    Ryan Butts

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  1. Ryan Butts
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  2. Andrew M. Atz
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  3. Nathanya BaezHernandez
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  4. David Sutcliffe
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  5. Joan Reisch
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  6. Lynn Mahony
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Contributions

All authors contributed to formation of the manuscript; authors RB, LM, and AA contributed to the study design; authors RB and LM contributed to recruitment of subjects; authors RB, DS, and NB performed study visits; authors RB and JR contributed to the data analysis.

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Correspondence to Ryan Butts.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Institutional Review Board at the University of Texas Southwestern.

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Informed consent and assent from all subjects or their guardians were obtained before enrollment.

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Butts, R., Atz, A.M., BaezHernandez, N. et al. Carvedilol Does Not Improve Exercise Performance in Fontan Patients: Results of a Crossover Trial. Pediatr Cardiol 42, 934–941 (2021). https://doi.org/10.1007/s00246-021-02565-6

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  • DOI: https://doi.org/10.1007/s00246-021-02565-6

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