Myocardial recovery and the failing heart: myth, magic, or molecular target?

Abstract

Medical and device therapies that reduce heart failure morbidity and mortality also lead to decreased left ventricular volume and mass and a more normal elliptical shape of the ventricle. These are due to changes in myocyte size, structure, and organization that have been referred to collectively as reverse remodeling. Moreover, there are subsets of patients whose hearts have undergone reverse remodeling either spontaneously or after medical or device therapies and whose clinical course is associated with freedom from future heart failure events. This phenomenon has been referred to as myocardial recovery. Despite the frequent interchangeable use of the terms "myocardial recovery" and "reverse remodeling" to describe the reversal of various aspects of the heart failure phenotype after medical and device therapy, the literature suggests that there are important differences between these 2 phenomena and that myocardial recovery and reverse remodeling are not synonymous. In this review, we discuss the biology of cardiac remodeling, cardiac reverse remodeling, and myocardial recovery with the intent to provide a conceptual framework for understanding myocardial recovery.

Figure 1

Reverse remodeling in clinical settings. Reverse remodeling is observed in a variety of clinical settings, as shown in the middle ring of the diagram. The segments illustrated in the outermost ring highlight the pathophysiological processes implicated by reverse remodeling in each particular clinical setting. (Abbreviations: ALM, acute lymphocytic myocarditis; CPAP, continuous positive airway pressure; RAAS, renin–angiotensin–aldosterone system; LVAD, left ventricular assist device; MVR, mitral valve repair/replacement; AVR, aortic valve replacement; CSD, cardiac support device; CRT, cardiac resynchronization therapy). (Adapted from Hellawell and Margulies(6) with permission)

Figure 2

Mechanical engineering science and cardiac remodeling. A) Diagram of a stress-strain curve of a ductile material, illustrating the relationship between an applied force (stress) and deformation (strain). Deformation can lead to reversible changes in a material (elastic deformation) if the properties of the material are not changed, and irreversible changes in a material (plastic deformation). B) Hypothetical model of reverse remodeling in heart that has undergone irreversible damage (plastic deformation). C) Hypothetical model of reverse remodeling with recovery in heart that has undergone reversible damage (elastic deformation).

Figure 3

Reverse remodeling and myocardial recovery. Cardiac remodeling arises secondary to abnormalities that arise in the biology of the cardiac myocyte (C), the myocardium (cardiocytes and extracellular matrix [M]), as well as LV geometry (LV), which have collectively been referred to as the heart failure phenotype. During reverse remodeling there is a reversal of the abnormalities in the cardiac myocyte, as well as the extracellular matrix, leading to a reversal of the abnormalities in LV geometry. Reverse remodeling can lead to two clinical outcomes (1) myocardial recovery, characterized by freedom from future cardiac events, or (2) myocardial remission, which is characterized by recurrence of heart failure events.