Cardiac metabolism - a promising therapeutic target for heart failure

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Cardiac metabolism - a promising therapeutic target for heart failure. / Noordali, Hannah; Loudon, Brodie; Frenneaux, Michael; Madhani, Melanie.

In: Pharmacology & Therapeutics, 2017.

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@article{b3a62c5345ef4b9d847ba35bab2c8975,
title = "Cardiac metabolism - a promising therapeutic target for heart failure",
abstract = "Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.",
keywords = "Cardiac metabolism, Heart failure, Heart failure with reduced ejection fraction (HFrEF), Heart failure with preserved ejection fraction (HFpEF), Metabolic modulation",
author = "Hannah Noordali and Brodie Loudon and Michael Frenneaux and Melanie Madhani",
year = "2017",
doi = "10.1016/j.pharmthera.2017.08.001",
language = "English",
journal = "Pharmacology & Therapeutics",
issn = "0163-7258",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Cardiac metabolism - a promising therapeutic target for heart failure

AU - Noordali, Hannah

AU - Loudon, Brodie

AU - Frenneaux, Michael

AU - Madhani, Melanie

PY - 2017

Y1 - 2017

N2 - Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.

AB - Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.

KW - Cardiac metabolism

KW - Heart failure

KW - Heart failure with reduced ejection fraction (HFrEF)

KW - Heart failure with preserved ejection fraction (HFpEF)

KW - Metabolic modulation

U2 - 10.1016/j.pharmthera.2017.08.001

DO - 10.1016/j.pharmthera.2017.08.001

M3 - Article

JO - Pharmacology & Therapeutics

JF - Pharmacology & Therapeutics

SN - 0163-7258

ER -