AN OMIC APPROACH TO THE EVALUATION OF METABOLIC IMPACT OF CARDIAC REHABILITATION IN POST-MYOCARDIAL INFARCTION PATIENTS

Objective: The beneficial effects of cardiac rehabilitation (CR) after acute ST-elevated myocardial infarction (STEMI) are estabilished, but so far little information is available on CR influence on the metabolic processes after myocardial infarction. Metabolomics is a semi-quantitative analysis of the body metabolic responses to pathophysiological stimuli or genetic alterations. Many metabolites have been associated with cardiovascular risk, and exercise-induced metabolomic changes were observed in athletes, in obesity and in metabolic syndrome. Aim of this project was to evaluate the metabolic response to physical training after STEMI. Design and method: We studied 25 non diabetic male patients aged < 75 years, initiating CR 4- 6 weeks after a first uncomplicated STEMI. Baseline data are shown in Table 1. CR consisted of 24±3 90-min sessions (warm-up, calisthenics and bicycling). Before and after CR we performed: colorDoppler echocardiogram (echo), 6-minutes walking test (6MWT) and blood tests [LDL, LP(a), Hb1Ac, CRP, homocysteine, BNP]. Metabolomic analysis was performed by Liquid Chromatography-Mass Spectrometry (LC-MS) on blood samples obtained on admission and at discharge from CR. Results: After CR, echo indexes improved (p<0.05): LVEF to 52.2±5.9%, WMSI to 1.46±0.28 and GLS to -14.2±3.2. At blood tests, CRP and BNP were reduced by 40% and 35% (p< 0.05). Distance at 6MWT increased (613±66 from 559±73 mt, p<0.01). Metabolomic analysis showed a significant variation of the overall metabolome (Figure 1). Metabolites affected by CR clustered in various pathways: glucose-alanine cycle, TCA (Krebs) cycle, oxidation of branched chain fatty acids, cysteine, alanine and pyruvate metabolisms. Some changes are related to physical exercise (i.e. hypoxanthine and pyruvate); others (i.e. allantoin) reflect oxidative stress which, if moderate, might induce cytoprotective mechanisms. Of interest was the increase in N-acetyl-Tyrosine, since its synthesis, triggered by mild oxidation, is reported to promote “mitohormesis” (adaptive changes in mitochondrial biogenesis).Conclusions: These preliminary data confirm the clinical benefits of CR. Moreover, they show significant changes in the metabolome, potentially indicative of adaptive responses to stress. Of note, this conclusion has been achieved through an “omic” (non-hypothesis driven) approach, best suited to unbiased assessment of CR effects in patients with a recent myocardial infarction.