Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure

Abstract

LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.

Clinical Decision Support System for Optimal Vad Weaning

“…Based on these parameters, they found that ventricular function did improve in patients after being supported by a VAD [19]. Several studies have also shown that unloading is associated with better myocyte function and the reversal of abnormal gene expressions; improved myocyte contractile properties and normalization of genes that regulate brain natriuretic peptide, calcium handling, tumor necrosis factor alpha and cytoskeleton proteins has been demonstrated [6][7][8][9][10].…”

“…In addition to providing circulatory support, studies report that by unloading the native ventricle with a VAD, the myocardium "reverse remodels" and indices of cardiac function improve [1][2][3][4][5][6][7][8][9][10][11].…”

Ventricular Assist Device: Emerging Modality for Long Term Cardiac Support

“…After VAD treatment, cardiomyocyte contractility is increased 26,27 and the force-frequency relationship is normalized. 28,29 Action-potential duration is reduced, 30,31 mirroring the shortening of the QT interval on electrocardiogram in patients after prolonged support. 32 In addition to E-C coupling mechanisms, several other molecular mechanisms responsible for VAD-induced reverse remodeling have been described.…”

Morphological and molecular changes of the myocardium after left ventricular mechanical support

“…Downregulated gene expression of sarcoplasmic endoreticular Ca 2+ exchanger have been reported and appear to correlate with contractile dysfunction [50]. After LVAD support, several authors indicate a recovery of cardiomyocyte contractile strength, coinciding with normalization of magnitude and time course of the Ca 2+ transient as well as an increased gene expression and protein level of SERCA2a [51,52]. Terracciano and co-workers have demonstrated that clinical recovery from terminal CHF after pharmacological and mechanical support is associated with modifications in excitation-contraction coupling, and sarcoplasmatic Ca 2+ homeostasis in particular, and not with a reduction of cardiomyocyte cell size.…”