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Cardiac contractility modulation in patients with heart failure — A review of the literature

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Abstract

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

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Funding

This work was supported by the RICBAC Foundation, NIH grants 1 R01 HL135335-01, 1 R21 HL137870-01, 1 R21EB026164-01, 3R21EB026164-02S1, and R01HL161008 awarded to Antonis A. Armoundas.

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Author notes

  1. Gary Tse and Antonis A. Armoundas have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Larnaca General Hospital, Inomenon Polition Amerikis, Larnaca, Cyprus

    George Bazoukis, Polyxeni Efthymiou & Andronicos Yiannikourides

  2. Medical School, European University Cyprus, Nicosia, Cyprus

    George Bazoukis & Konstantinos Lampropoulos

  3. Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece

    Athanasios Saplaouras, Konstantinos P. Letsas & Michael Efremidis

  4. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China

    Tong Liu & Gary Tse

  5. Second Department of Cardiology, Evangelismos General Hospital, Athens, Greece

    Sotirios Xydonas

  6. Kent and Medway Medical School, University of Kent, Canterbury, Kent, UK

    Gary Tse

  7. Canterbury Christ Church University, Canterbury, Kent, UK

    Gary Tse

  8. School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China

    Gary Tse

  9. Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA, 02129, USA

    Antonis A. Armoundas

  10. Broad Institute, Massachusetts Institute of Technology, Cambridge, MA, USA

    Antonis A. Armoundas

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  1. George Bazoukis
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Contributions

George Bazoukis: Wrote the first draft, major revisions, approval of the final manuscript.  Athanasios Saplaouras: major revisions, approval of the final manuscript.  Polyxeni Efthymiou: major revisions, approval of the final manuscript.  Andronikos Yannikourides: major revisions, approval of the final manuscript.  Tong Liu: major revisions, approval of the final manuscript.  Konstantinos P Letsas: major revisions, approval of the final manuscript.  Michael Efremidis: major revisions, approval of the final manuscript.  Konstantinos Lampropoulos: major revisions, approval of the final manuscript.  Sotirios Xydonas: major revisions, approval of the final manuscript.  Gary Tse: supervision, major revisions, approval of the final manuscript.  Antonis A. Armoundas: Supervision, major revisions, approval of the final manuscript.

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Correspondence to George Bazoukis or Antonis A. Armoundas.

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Bazoukis, G., Saplaouras, A., Efthymiou, P. et al. Cardiac contractility modulation in patients with heart failure — A review of the literature. Heart Fail Rev 29, 689–705 (2024). https://doi.org/10.1007/s10741-024-10390-1

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