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Cardiac Contractility Modulation in a Model of Repaired Tetralogy of Fallot: A Sheep Model

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Abstract

The onset of right ventricular dysfunction in patients presenting with congenital heart disease is associated with a dismal long-term outcome and often represents a therapeutic dead end. Our study had several objectives: (1) to analyse the anatomical, functional, histological and cellular characteristics of an animal model of repaired tetralogy of Fallot with right ventricular dysfunction (2) to test the new electrical treatment known as cardiac contractility modulation in this animal model. Seven sheep underwent a first surgery at the age of three weeks aiming to mimic the characteristics of a repaired tetralogy of Fallot. Five controls were sham-operated. Experimental studies were performed 12 months after the initial operation. The hemodynamic, echocardiographic, and mitochondrial function studies were carried out before and after cardiac contractility modulation in closed- and open-chest conditions. In this animal model of right ventricular dysfunction, short-term cardiac contractility modulation was associated with a significant improvement in (a) right ventricular function, as evidenced by a significant increase in right ventricular dP/dt (p < 0.05) (b) left ventricular function evidenced by the increase in left ventricular dP/dt max (p < 0.05) (c) in mitochondrial function (p < 0.05). In this animal model of chronic right ventricular dysfunction, cardiac contractility modulation significantly improved acute cardiac hemodynamic and mitochondrial functions of both ventricles and may represent a promising option in patients with right heart failure.

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Acknowledgments

This study was supported by the French Government, Agence Nationale de la Recherche au titre du programme Investissements d’Avenir (Grant No. ANR-10-IAHU-04).

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Authors and Affiliations

  1. University of Bordeaux 2, 33000, Bordeaux, France

    Francois Roubertie, Romain Eschalier, Adlane Zemmoura, Jean-Benoit Thambo, Louis Labrousse, Sylvain Ploux, Philippe Ritter, Michel Haïssaguerre, Pierre Dos Santos & Pierre Bordachar

  2. University Hospital of Bordeaux, 33000, Bordeaux, France

    Francois Roubertie, Romain Eschalier, Adlane Zemmoura, Jean-Benoit Thambo, Louis Labrousse, Sylvain Ploux, Philippe Ritter, Michel Haïssaguerre, Pierre Dos Santos & Pierre Bordachar

  3. L’institut de rythmologie et modélisation cardiaque (LIRYC), Université Bordeaux, Bordeaux, France

    Francois Roubertie, Romain Eschalier, Adlane Zemmoura, Jean-Benoit Thambo, Louis Labrousse, Sylvain Ploux, Philippe Ritter, Michel Haïssaguerre, Pierre Dos Santos & Pierre Bordachar

  4. University of Bordeaux, Maladies Rares: Génétique et Métabolisme (MRGM), EA 4576, 33000, Bordeaux, France

    Caroline Rooryck

  5. Cardiology Department, CHU Clermont-Ferrand, 63003, Clermont-Ferrand, France

    Romain Eschalier

  6. Clermont Université, ISIT-CaVITI, BP 10448, 63001, Clermont-Ferrand, France

    Romain Eschalier

Authors
  1. Francois Roubertie
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  2. Romain Eschalier
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  3. Adlane Zemmoura
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  4. Jean-Benoit Thambo
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  5. Caroline Rooryck
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  6. Louis Labrousse
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  7. Sylvain Ploux
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  8. Philippe Ritter
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  9. Michel Haïssaguerre
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  10. Pierre Dos Santos
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  11. Pierre Bordachar
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Correspondence to Pierre Bordachar.

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Roubertie, F., Eschalier, R., Zemmoura, A. et al. Cardiac Contractility Modulation in a Model of Repaired Tetralogy of Fallot: A Sheep Model. Pediatr Cardiol 37, 826–833 (2016). https://doi.org/10.1007/s00246-016-1356-0

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  • DOI: https://doi.org/10.1007/s00246-016-1356-0

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