Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.

Structured Abstract Objectives To evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Background Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in HCM, no prior study has evaluated the effects of angiotensin receptor blockers (ARBs) on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging (CMR). Methods In double-blind fashion, 20 patients (3 women; age 51±13 years) with HCM were randomly assigned to receive placebo (n=9) or losartan 50 mg twice a day (n=11) for 1 year. CMR was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement (LGE). Results There was a trend towards a significant difference in the percent change in LV mass (median [interquartile range], +5 [−4, +21] % on placebo vs. −5 [−11, −0.9] % on losartan; p=0.06). There was a significant difference in the percent change in extent of LGE, with the placebo group having larger increase (+31 ± 26 % on placebo vs. −23 ± 45 % on losartan; p=0.03). Conclusions This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis by losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for ARBs in the management of HCM.

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