Biology of myocardial recovery in advanced heart failure with long-term mechanical support

Eleni Tseliou, Kory J. Lavine, Omar Wever-Pinzon, Veli K. Topkara, Bart Meyns, Iki Adachi, Daniel Zimpfer, Emma J. Birks, Daniel Burkhoff, Stavros G. Drakos

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cardiac remodeling is an adaptive, compensatory biological process following an initial insult to the myocardium that gradually becomes maladaptive and causes clinical deterioration and chronic heart failure (HF). This biological process involves several pathophysiological adaptations at the genetic, molecular, cellular, and tissue levels. A growing body of clinical and translational investigations demonstrated that cardiac remodeling and chronic HF does not invariably result in a static, end-stage phenotype but can be at least partially reversed. One of the paradigms which shed some additional light on the breadth and limits of myocardial elasticity and plasticity is long term mechanical circulatory support (MCS) in advanced HF pediatric and adult patients. MCS by providing (a) ventricular mechanical unloading and (b) effective hemodynamic support to the periphery results in functional, structural, cellular and molecular changes, known as cardiac reverse remodeling. Herein, we analyze and synthesize the advances in our understanding of the biology of MCS-mediated reverse remodeling and myocardial recovery. The MCS investigational setting offers access to human tissue, providing an unparalleled opportunity in cardiovascular medicine to perform in-depth characterizations of myocardial biology and the associated molecular, cellular, and structural recovery signatures. These human tissue findings have triggered and effectively fueled a “bedside to bench and back” approach through a variety of knockout, inhibition or overexpression mechanistic investigations in vitro and in vivo using small animal models. These follow-up translational and basic science studies leveraging human tissue findings have unveiled mechanistic myocardial recovery pathways which are currently undergoing further testing for potential therapeutic drug development. Essentially, the field is advancing by extending the lessons learned from the MCS cardiac recovery investigational setting to develop therapies applicable to the greater, not end-stage, HF population. This review article focuses on the biological aspects of the MCS-mediated myocardial recovery and together with its companion review article, focused on the clinical aspects, they aim to provide a useful framework for clinicians and investigators.

Original languageEnglish
Pages (from-to)1309-1323
Number of pages15
JournalJournal of Heart and Lung Transplantation
Volume41
Issue number10
DOIs
StatePublished - Oct 2022

Bibliographical note

Funding Information:
Stavros Drakos has received consulting fee from Abbott and Arena Pharmaceuticals and grant support from Merck, Novartis and NIH (RO1HL135121, RO1HL156667, RO1HL151924-01, 1K23HL150322-01A1 and T32HL007576). The rest authors have no relevant disclosures.

Publisher Copyright:
© 2022 International Society for Heart and Lung Transplantation

Keywords

  • GDMT
  • LVAD
  • biology
  • explant
  • myocardial recovery

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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