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Soluble Neprilysin?- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

ABSTRACT: Background: Circulating soluble neprilysin (sNEP) predicts outcome in heart failure (HF) patients with reduced ejection fraction (EF), but not in those with preserved EF. We examined sNEP in patients with hypertrophic cardiomyopathy (HCM), and their correlations with other biomarkers, cardiac function, and clinical outcome. Methods?and?Results: We examined the associations between sNEP and the laboratory and echocardiography parameters in the HCM patients (n=93). Regarding the laboratory data, sNEP had a significant positive correlation with B-type natriuretic peptide (BNP; R=0.326, P=0.003), but not with troponin I. As for the echocardiographic parameters, sNEP negatively correlated with left ventricular EF (R=-0.283, P=0.009) and right ventricular fractional area change (R=-0.277, P=0.012), but not with left ventricular mass. Next, we prospectively followed up on the patients for cardiac events, including worsening HF or cardiac death, and all-cause mortality. On Kaplan-Meier analysis (mean follow-up, 1,021 days), the cardiac event rate and all-cause mortality were similar between the higher sNEP group (sNEP ?median level of 1.43 ng/mL, n=46) and lower sNEP group (sNEP <1.43 ng/mL, n=47). On Cox proportional hazard analysis, sNEP was not a predictor of cardiac event or all-cause mortality. Conclusions: Soluble neprilysin appears to correlate with BNP and cardiac systolic function, but it is not significantly associated with prognosis in HCM patients.

SUBMITTER: Yoshihisa A

PROVIDER: S-EPMC7889477 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Soluble Neprilysin　- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

Yoshihisa Akiomi A Yokokawa Tetsuro T Ichijo Yasuhiro Y Kimishima Yusuke Y Kanno Yuki Y Misaka Tomofumi T Sato Takamasa T Oikawa Masayoshi M Kobayashi Atsushi A Yamaki Takayoshi T Sugimoto Koichi K Kunii Hiroyuki H Takeishi Yasuchika Y

Circulation reports 20190521 6

Background: Circulating soluble neprilysin (sNEP) predicts outcome in heart failure (HF) patients with reduced ejection fraction (EF), but not in those with preserved EF. We examined sNEP in patients with hypertrophic cardiomyopathy (HCM), and their correlations with other biomarkers, cardiac function, and clinical outcome. Methods and Results: We examined the associations between sNEP and the laboratory and echocardiography parameters in the HCM patients (n=93). Rega ...[more]

PMID: 33693148

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Project description:BackgroundHypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM.MethodsWe performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts).ResultsIntegrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance.ConclusionsOverall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

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Soluble Neprilysin?- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

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Soluble Neprilysin　- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

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Dataset Information

Soluble Neprilysin?- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

Publications

Soluble Neprilysin - Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Soluble Neprilysin　- Cardiac Function and Outcome in Hypertrophic Cardiomyopathy.