Myocardial Reverse Remodeling

Abstract

SUMMARYDespite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse process, often labeled reverse remodeling. Accordingly, the goal of this review is to overview the varied settings in which clinically significant reverse remodeling has been well documented. When available, we reviewed relevant randomized, controlled clinical trials, and meta-analyses with sufficient cardiac imaging data to permit conclusions about reverse remodeling. When these types of studies were not available, relevant case-control studies and case series that employed appropriate methodology were reviewed. Regression of pathological myocardial hypertrophy, chamber shape distortions, and dysfunction occurs in a wide variety of settings. Although reverse remodeling occurs spontaneously in some etiologies of myocardial dysfunction and failure, remodeling is more commonly observed in response to medical, device-based, or surgical therapies, including β-blockers, revascularization, cardiac resynchronization therapy, and valve surgery. Indeed, reverse remodeling following pathophysiologically targeted interventions helps validate that the targeted mechanisms are propelling and/or sustaining pathological remodeling. The diverse clinical settings in which reverse remodeling has been observed demonstrates that myocardial remodeling is bidirectional and occurs across the full spectrum of myocardial disease severity, duration, and etiology. Observations in several settings suggest that recovered hearts are not truly normal despite parallel improvements at organ, tissue, and cellular level. Nevertheless, the link between reverse remodeling and improved outcomes should inspire further research to better understand the mechanisms responsible for both reverse remodeling and persistent deviations from normalcy.

Ginseng Reverses Established Cardiomyocyte Hypertrophy and Postmyocardial Infarction-Induced Hypertrophy and Heart Failure

“…6,21,22 The present study supports the underlying hypothesis that myocardial remodeling is a bidirectional process that can be reversed by pharmacotherapy independently of load reduction, such as that observed with therapeutic devices. 6 The key role for cardiac hypertrophy as a target for ginseng-induced reversibility is supported by a direct reversal of hypertrophy in cultured myocytes exposed to 3 different prohypertrophic agents. Moreover, cardiac dysfunction in control animals subjected to CAL was accompanied by both gravimetric and gene analyses data, indicating a hypertrophic phenotype.…”

“…Reversal of cardiac hypertrophy remains a major therapeutic challenge but one that is critical for the development of improved therapeutic strategies for treating heart failure. 6 The results based on findings in cultured myocytes and in vivo heart failure as well as evidence in the literature 12 suggest that reversal of calcineurin-dependent processes represents a viable mechanistic basis for the reversal of hypertrophy. The results, therefore, reinforce the concept that targeting the calcineurin pathway may represent a key approach toward developing effective therapeutic strategies, although it is recognized that other potential intracellular targets for reversal of hypertrophy likely exist and cannot be excluded.…”

“…5 The high mortality rate associated with heart failure likely reflects the complexity of the myocardial remodeling processes that contribute to heart failure and the difficulty in reversing these processes with current pharmacotherapy. 6 …”

Naringenin attenuates pressure overload-induced cardiac hypertrophy

“…Preventing and postponing the progression of cardiac hypertrophy may serve as an effective therapeutic strategy for the treatment of patients with heart failure (2). Clinical management of pathological cardiac hypertrophy is targeted against the underlying cause of the condition and typically involves the administration of certain pharmacological agents, such as angiotensin-converting-enzyme inhibitor and angiotensin receptor blockers (3). However, although current pharmacological approaches appear to be beneficial in improving the quality of life of patients with heart failure, they do not markedly reduce the mortality rates (4).…”

Magnetic Resonance Imaging of Reverse Remodeling After Coronary Revascularization in Ischemic Heart Disease – Morphologic Evaluation –

“…20 Coronary revascularization has been shown to induce LV RR, especially in patients with a substantial amount of viable myocardium. 21 Indeed, sequential CMR after surgical revascularization has indicated significant improvements in global LV systolic function and reduction of LV volume in a subset of patients with viable myocardium, indicative of myocardial RR.…”