Basic science of cardiac contractility modulation therapy: Molecular and electrophysiological mechanisms

In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactiv...

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Published inHeart rhythm Vol. 21; no. 1; pp. 82 - 88
Main Authors Masarone, Daniele, Kittleson, Michelle M., D’Onofrio, Antonio, Falco, Luigi, Fumarulo, Isabella, Massetti, Massimo, Crea, Filippo, Aspromonte, Nadia, Pacileo, Giuseppe
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.01.2024
Subjects
Calcium
Calcium handling
Cardiac contractility modulation therapy
Cardiotonic Agents
Fibrosis
Heart Failure - drug therapy
Heart failure with preserved ejection fraction
Heart failure with reduced ejection fraction
Humans
Molecular mechanism
Myocardial Contraction - physiology
Stroke Volume - physiology
Ventricular Dysfunction, Left
Heart failure with preserved ejection fraction
Ryr2
CRT
Cardiac contractility modulation therapy
Molecular mechanism
PLB
Heart failure with reduced ejection fraction
HFpEF
SERCA
HFrEF
FAO
CCMT
Calcium handling
ATP
HF
SR
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Abstract In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure–associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy. [Display omitted]
AbstractList In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure-associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy.
In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure–associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy. [Display omitted]
In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure-associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy.In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure-associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy.
Author D’Onofrio, Antonio
Crea, Filippo
Falco, Luigi
Massetti, Massimo
Fumarulo, Isabella
Masarone, Daniele
Aspromonte, Nadia
Kittleson, Michelle M.
Pacileo, Giuseppe
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– sequence: 4
  givenname: Luigi
  surname: Falco
  fullname: Falco, Luigi
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  organization: Catholic University of the Sacred Heart, Rome, Italy
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  organization: Catholic University of the Sacred Heart, Rome, Italy
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  fullname: Aspromonte, Nadia
  organization: Catholic University of the Sacred Heart, Rome, Italy
– sequence: 9
  givenname: Giuseppe
  surname: Pacileo
  fullname: Pacileo, Giuseppe
  organization: Heart Failure Unit, Department of Cardiology, AORN dei Colli/Monaldi Hospital, Naples, Italy
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Keywords Heart failure with preserved ejection fraction
Ryr2
CRT
Cardiac contractility modulation therapy
Molecular mechanism
PLB
Heart failure with reduced ejection fraction
HFpEF
SERCA
HFrEF
FAO
CCMT
Calcium handling
ATP
HF
SR
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Snippet In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been...
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SubjectTerms Calcium
Calcium handling
Cardiac contractility modulation therapy
Cardiotonic Agents
Fibrosis
Heart Failure - drug therapy
Heart failure with preserved ejection fraction
Heart failure with reduced ejection fraction
Humans
Molecular mechanism
Myocardial Contraction - physiology
Stroke Volume - physiology
Ventricular Dysfunction, Left
Title Basic science of cardiac contractility modulation therapy: Molecular and electrophysiological mechanisms
URI https://www.clinicalkey.com/#!/content/1-s2.0-S1547527123027674
https://www.ncbi.nlm.nih.gov/pubmed/37769793
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Volume 21
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