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Cardiac contractility modulation: an effective treatment strategy for heart failure beyond reduced left ventricular ejection fraction?

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Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) causes a progressive limitation of functional capacity, poor quality of life (QoL) and increased mortality, yet unlike HF with reduced ejection fraction (HFrEF) there are no effective device-based therapies. Both HFrEF and HFpEF are associated with dysregulations in myocardial cellular calcium homeostasis and modifications in calcium-handling proteins, leading to abnormal myocardial contractility and pathological remodelling. Cardiac contractility modulation (CCM) therapy, based on a pacemaker-like implanted device, applies extracellular electrical stimulation to myocytes during the absolute refractory period of the action potential, which leads to an increase in cytosolic peak calcium concentrations and thereby the force of isometric contraction promoting positive inotropism. Subgroup analysis of CCM trials in HFrEF has demonstrated particular benefits in patients with LVEF between 35% and 45%, suggesting its potential effectiveness also in patients with higher LVEF values. Available evidence on CCM in HFpEF is still preliminary, but improvements in terms of symptoms and QoL have been observed. Future large, dedicated, prospective studies are needed to evaluate the safety and efficacy of this therapy in patients with HFpEF.

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Authors and Affiliations

  1. Institute of Cardiology, ASST Spedali Civili di Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy

    Mauro Riccardi, Antonio M. Sammartino, Marianna Adamo, Riccardo M. Inciardi, Carlo M. Lombardi, Daniela Tomasoni, Enrico Vizzardi, Marco Metra & Matteo Pagnesi

  2. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Nicola R. Pugliese

  3. Heart Research Institute, Sydney, Australia

    Andrew J. S. Coats

Authors
  1. Mauro Riccardi
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  2. Antonio M. Sammartino
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  3. Marianna Adamo
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Contributions

Dr. Riccardi and Dr. Pagnesi designed the review. Dr. Riccardi, Dr. Sammartino and Dr. Pagnesi performed manuscript drafting. Dr. Riccardi, Dr. Sammartino, Dr. Adamo, Dr. Inciardi, Dr. Lombardi, Dr. Pugliese, Dr. Tomasoni, Dr. Vizzardi, Dr. Metra, Dr. Coats and Dr. Pagnesi permorfed manuscript revision and provided value intellectual contribution.

Corresponding author

Correspondence to Marco Metra.

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Competiting interests

Dr. Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr. Metra has received consulting honoraria as a member of trial committees or advisory boards for Abbott Vascular, Actelion, Amgen, Bayer, Edwards Therapeutics, Servier, Vifor Pharma and Windtree Therapeutics. Dr. Coats has received honoraria and/or lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia and Viatris. Dr. Pagnesi has received personal fees from Abbott Vascular, AstraZeneca, Boehringer Ingelheim and Vifor Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Riccardi, M., Sammartino, A.M., Adamo, M. et al. Cardiac contractility modulation: an effective treatment strategy for heart failure beyond reduced left ventricular ejection fraction?. Heart Fail Rev 28, 1141–1149 (2023). https://doi.org/10.1007/s10741-023-10315-4

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