The Modulating Effects of Cardiac Resynchronization Therapy on Myocardial Metabolism in Heart Failure

Abstract

Heart failure (HF) is associated with changes in cardiac substrate utilization and energy metabolism, including a decline in high-energy phosphate content, mitochondrial dysfunction, and phosphotransfer enzyme deficiency. A shift toward glucose metabolism was noted in the end stage of HF in animals, although HF in humans may not be associated with a shift toward predominant glucose utilization. Deficiencies of micronutrients are well-established causes of cardiomyopathy. Correction of these deficits can improve heart function. The genes governing the energy metabolism were predominantly under-expressed in nonischemic cardiomyopathy and hypertrophic cardiomyopathy but were overexpressed in ischemic cardiomyopathy. Cardiac resynchronization therapy (CRT) has been proven to increase cardiac efficiency without increasing myocardial oxygen consumption. Altered myocardial metabolism is normalized by CRT to improve ventricular function.

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism

“…By applying different analytic techniques, such as nuclear magnetic resonance spectroscopy (NMR) or mass spectrometry (MS), metabolomics allows identifying and quantifying a high number of metabolites in a sample. Despite the known impairment of metabolism in patients with heart failure, both locally (Xu et al 2016 ) as well systemically (Hunter et al 2016 ), metabolomics studies were conducted only on atrial tissue but not on plasma samples of patients with AF so far (Mayr et al 2008 ). Similarly, neither the effect of the termination of AF (either electrically or pharmaceutically) nor of the exclusion of LAA from the circulation by surgery or device implantation has been studied yet.…”

“…They comprised metabolites of the utilization of ketone bodies and of the tricarboxylic acid (TCA) cycle as well as glycolytic enzymes (Mayr et al 2008 ). The effects of different cardiac interventions either locally on gene or protein expression or systemically have been described several times (McManus et al 2015 ; Navaravong et al 2015 ; Huang et al 2014 ; Xu et al 2016 ; Nemutlu et al 2015 ). In the current study, we tested whether successful interventional LAA closure (LAAC) would change the systemic metabolomic profile of patients with AF.…”

Circulating metabolite profiles to predict response to cardiac resynchronization therapy

“…The optimal cutoff value was obtained (0.5276) and applied to evaluate the prediction capacity of the current model. In validation set, QRS duration (orange curve) has an AUC of 0.643 (95% CI: 0.486-0.799) and metabolic panel (blue curve) has an AUC of 0.929 (95% CI: 0.864-0.994) compensation [11,22]. On the other hand, Colak et al [23] discovered that genes involved in energy metabolic processes, such as the citric acid cycle and adenosine triphosphate synthesis, were upregulated in DCM patients.…”

Key Genes and Pathways in Human Left Atrial Appendage Identified by Co-expression Analysis

“…It is known that intracardiac device implantation procedures like cardiac resynchronization therapy (CRT), are linked with post procedural changes on hemodynamic, metabolic and endocrine pro les (ref), in fact, these changes were also observed among patients post LAAC. 1 Intriguingly, in "LAA HOMEOSTASIS" study, 2 a prospective observational study, which compared the differences between patients with epicardial and endocardial LAAC, revealed more apparent neurohormonal changes in patients undergoing epicardial LAAC, especially on the renin-angiotensin-aldosterone system (RAAS), lipid and glucose metabolism, systemic blood pressure and natriuretic peptide levels. Since the difference between the two approaches is directly based on whether LAA is conserved or excluded, the physiological role of LAA on this process is highlighted.…”