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Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation Outcomes of patients with and without baseline lipid-lowering therapy undergoing revascularization for left main coronary artery disease: analysis from the EXCEL trial 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC) Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study Influence of Heart Rate on FFR Measurements: An Experimental and Clinical Validation Study EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion – an update A prediction model of simple echocardiographic variables to screen for potentially correctable shunts in adult patients with pulmonary arterial hypertension associated with atrial septal defects: a cross-sectional study OCT compared with IVUS in a coronary lesion assessment: the OPUS-CLASS study Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW
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Original Research2020 Dec 11;S1550-4131(20)30658-6.

JOURNAL：Cell Metab. Article Link

The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

AA Cluntun, R Badolia, SG Drakos et al. Keywords: LVAD; MCT4; MPC; VB124; cardiac metabolism; heart failure; hypertrophy; lactate; mitochondria; pyruvate

ABSTRACT

The metabolic rewiring of cardiomyocytes is a widely accepted hallmark of heart failure (HF). These metabolic changes include a decrease in mitochondrial pyruvate oxidation and an increased export of lactate. We identify the mitochondrial pyruvate carrier (MPC) and the cellular lactate exporter monocarboxylate transporter 4 (MCT4) as pivotal nodes in this metabolic axis. We observed that cardiac assist device-induced myocardial recovery in chronic HF patients was coincident with increased myocardial expression of the MPC. Moreover, the genetic ablation of the MPC in cultured cardiomyocytes and in adult murine hearts was sufficient to induce hypertrophy and HF. Conversely, MPC overexpression attenuated drug-induced hypertrophy in a cell-autonomous manner. We also introduced a novel, highly potent MCT4 inhibitor that mitigated hypertrophy in cultured cardiomyocytes and in mice. Together, we find that alteration of the pyruvate-lactate axis is a fundamental and early feature of cardiac hypertrophy and failure.
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