Are there potential biological differences that may explain the disparate clinical outcomes that occur after reverse remodeling? Although the potential biological differences between myocardial recovery and myocardial remission are not known, there are parallels in mechanical engineering science that may help to illuminate potential important differences as well as to frame future mechanistic discussions. In mechanics, deformation of a material refers to the change in the shape or size of an object due to an applied force. (Figure 62_gr2)A shows an example of a stress versus strain diagram of a material that is exposed to an increased load. With increasing stress, there is an increase in the length of the material until the point when no further changes in length are possible without the material breaking. Importantly, if the material returns to its original state when the load is removed, this is referred to as elastic deformation. In contrast, if during the application of stress the mechanical properties of the material are changed irreversibly, such that the object will return only part way to its original shape when the stress is removed, this is referred to as plastic deformation. It is sometimes the case that elastic deformation occurs under a certain level of stress and plastic deformation occurs when that stress level is exceeded. Regardless, the important distinction is whether the material returns to its original state when the stress is removed. Although precise parallels between cardiac remodeling in heart failure and deformation of solid materials after loading are not appropriate, there could be a heuristic parallel between reverse remodeling and plastic deformation, inasmuch as the reverse remodeled heart does not revert completely to normal after cessation of hemodynamic overloading (Figure 62_gr2B). Although speculative, it is possible that myocardial recovery is more analogous to elastic deformation in that the recovered heart reverts to normal after hemodynamic overloading is removed (Figure 62_gr2C). Thus, we propose that reverse remodeling without recovery represents a reversal of the heart failure phenotype that occurs in hearts that have sustained irreversible damage, whereas myocardial recovery represents a reversal of the heart failure phenotype that occurs in hearts that have reversible damage (Figure 62_gr3). Although the biological motifs that separate reversible (elastic) from irreversible (plastic) changes in the heart are not known, it is likely that the progressive loss of cardiac myocytes, irreversible changes at the DNA level, and the progressive erosion of the native 3-dimensional organization of the ECM surrounding the cardiac myocytes will be critical determinants that distinguish between reverse remodeling and myocardial recovery ((5),13). The observation that the great majority of clinical examples of myocardial recovery in the literature occur after transient injury (e.g., viral infection, inflammation, toxic injury) rather than more long-standing and/or permanent injury (e.g., myocardial infarction, genetic abnormalities) is consistent with the point of view that the ability of the heart to “recover” is related to the nature of the inciting injury and the extent of underlying myocardial damage that occurs during the resolution of cardiac injury. This observation is also consistent with the observation from the LVAD bridge to recovery studies (Table 3), which have consistently shown that recovery is possible in patients with myocarditis and/or postpartum cardiomyopathy, whereas recovery does not occur in patients with irreversible damage from myocardial ischemia/infarction. It is also possible that myocardial recovery may represent a new and unique set of biological adaptations (e.g., changes in integrin signaling and β-adrenergic signaling) that are associated with better pump function and improved prognosis and that these unique adaptations explain the differences between myocardial recovery and remission ((6),(18),19).