2013
DOI: 10.1161/circresaha.113.301413
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Abstract: Abstract-Heart failure is associated with remodeling that consists of adverse cellular, structural, and functional changes in the myocardium. Until recently, this was thought to be unidirectional, progressive, and irreversible. However, irreversibility has been shown to be incorrect because complete or partial reversal can occur that can be marked after myocardial unloading with a left ventricular assist device (LVAD). Patients with chronic advanced heart failure can show near-normalization of nearly all struc… Show more

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Cited by 100 publications
(85 citation statements)
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“…Therefore, we sought to determine whether the therapeutic benefit of perhexiline in HF is related to an improved cardiac PCr/ATP ratio and whether this is a consequence of altered cardiac substrate utilization. Effective therapy for HF that does not act in the first instance by direct effects on cardiac metabolism may nevertheless in the longer term result in improvements in the cardiac PCr/ATP ratio via an improvement in HF syndrome, leading in turn to molecular reverse remodeling of maladaptive changes in genes involved in cardiac metabolism and calcium handling and thereby potentially to a virtuous cycle of improved cardiac function (11)(12)(13). In this study, we hypothesized that perhexiline therapy would improve the cardiac PCr/ATP ratio in patients with HF by altering cardiac substrate utilization.…”
mentioning
confidence: 99%
“…Therefore, we sought to determine whether the therapeutic benefit of perhexiline in HF is related to an improved cardiac PCr/ATP ratio and whether this is a consequence of altered cardiac substrate utilization. Effective therapy for HF that does not act in the first instance by direct effects on cardiac metabolism may nevertheless in the longer term result in improvements in the cardiac PCr/ATP ratio via an improvement in HF syndrome, leading in turn to molecular reverse remodeling of maladaptive changes in genes involved in cardiac metabolism and calcium handling and thereby potentially to a virtuous cycle of improved cardiac function (11)(12)(13). In this study, we hypothesized that perhexiline therapy would improve the cardiac PCr/ATP ratio in patients with HF by altering cardiac substrate utilization.…”
mentioning
confidence: 99%
“…[4][5][6][7] Likewise, mechanical unloading with left ventricular assist devices and resynchronization therapy have led to partial reversal of cardiac structural and molecular remodeling and symptomatic improvement. [8][9][10] Despite these remarkable advances, however, mortality and morbidity of patients with heart failure, with or without reduced ejection fraction remains high. 1,2 Moreover, heart transplantation, while an effective option, is available only for a selected number of patients and is not without considerable negative consequences.…”
mentioning
confidence: 99%
“…In her fine Review, Birks 95 describes morphological and molecular changes that occur in the hearts of patients on longterm LVADs. These include reverse remodeling of the left ventricle, regression of myocyte hypertrophy, reductions in elevated levels of circulating neurohormones, an increase in the density of β-adrenergic receptors, and an improvement of Ca 2+ cycling in the myocyctes.…”
Section: Left Ventricular Assist Device Support For Hfmentioning
confidence: 99%
“…Thus, although it seems sensible to rest an overloaded failing heart, prolonged unloading can exert deleterious effects, including cardiac atrophy as well as more extensive ventricular collagen crosslinking leading to increased myocardial stiffness. 95 Myocardial recovery has not been demonstrated with any regularity in patients with chronic ischemic heart disease, the most common cause of HF in industrialized nations. It is possible that earlier intervention in these patients and the aid of cell therapy may be necessary for reversal of HF.…”
Section: Left Ventricular Assist Device Support For Hfmentioning
confidence: 99%
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