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Temporal cardiac remodeling post-myocardial infarction: dynamics and prognostic implications in personalized medicine

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Abstract

Despite dramatic improvements in short-term mortality rates following myocardial infarction (MI), long-term survival for MI patients who progress to heart failure remains poor. MI occurs when the left ventricle (LV) is deprived of oxygen for a sufficient period of time to induce irreversible necrosis of the myocardium. The LV response to MI involves significant tissue, cellular, and molecular level modifications, as well as substantial hemodynamic changes that feedback negatively to amplify the response. Inflammation to remove necrotic myocytes and fibroblast activation to form a scar are key wound healing responses that are highly variable across individuals. Few biomarkers of early remodeling stages are currently clinically adopted. The discovery of underlying pathophysiological mechanisms and associated novel biomarkers has the potential of improving prognostic capability and therapeutic monitoring. Combining these biomarkers with other prominent ones could constitute a powerful diagnostic and prognostic tool that directly reflects the pathophysiological remodeling of the LV. Understanding temporal remodeling at the tissue, cellular, and molecular level and its link to a well-defined set of biomarkers at early stages post-MI is a prerequisite for improving personalized care and devising more successful therapeutic interventions. Here we summarize the integral mechanisms that occur during early cardiac remodeling in the post-MI setting and highlight the most prominent biomarkers for assessing disease progression.

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Abbreviations

ECM:

Extracellular matrix

IL:

Interleukin

LV:

Left ventricle

MI:

Myocardial infarction

MMPs:

Matrix metalloproteinases

SPARC:

Secreted protein acidic and rich in cysteine

TGFβ:

Tumor growth factor beta

VSMC:

Vascular smooth muscle cell

α1-PI:

Alpha-1 protease inhibitor

α2-MG:

Alpha 2-macroglobulin

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Acknowledgments

The authors would like to acknowledge Dr. Abdullah Kaplan for his careful review revisions, and valuable input. The authors appreciate the support of the Department of Pharmacology and Toxicology (UMMC).

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Correspondence to Fouad A. Zouein.

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Drs. Raffaele Altara, Marco Manca, Ramzi Sabra, Assaad A. Eid, George W. Booz and Fouad A. Zouein have no conflicts of interest or financial ties to disclose.

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Altara, R., Manca, M., Sabra, R. et al. Temporal cardiac remodeling post-myocardial infarction: dynamics and prognostic implications in personalized medicine. Heart Fail Rev 21, 25–47 (2016). https://doi.org/10.1007/s10741-015-9513-8

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  • DOI: https://doi.org/10.1007/s10741-015-9513-8

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