Targeting Metabolic Modulation and Mitochondrial Dysfunction in the Treatment of Heart Failure

TY - JOUR

T1 - Targeting Metabolic Modulation and Mitochondrial Dysfunction in the Treatment of Heart Failure

AU - Steggall, Abbey

AU - Mordi, Ify

AU - Lang, Chim

N1 - no funding info

PY - 2017/5/10

Y1 - 2017/5/10

N2 - Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability. Therefore, the development of potential metabolic therapeutics has commenced including trimetazidine, ranolazine and perhexiline, as well as specific mitochondrial-targeting pharmaceuticals, such as elamipretide. Large randomised controlled trials are required to confirm the role of metabolic-modulating drugs in the treatment of heart failure, but early studies have been promising in their possible efficacy for the management of heart failure in the future.

AB - Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability. Therefore, the development of potential metabolic therapeutics has commenced including trimetazidine, ranolazine and perhexiline, as well as specific mitochondrial-targeting pharmaceuticals, such as elamipretide. Large randomised controlled trials are required to confirm the role of metabolic-modulating drugs in the treatment of heart failure, but early studies have been promising in their possible efficacy for the management of heart failure in the future.

KW - heart failure

KW - metabolic

KW - mitochondria

KW - trimetazidine

KW - ranolazine

KW - perhexiline

KW - elamipretide

U2 - 10.3390/diseases5020014

DO - 10.3390/diseases5020014

M3 - Review article

C2 - 28933367

SN - 2079-9721

VL - 5

SP - 1

EP - 18

JO - Diseases

JF - Diseases

IS - 2

M1 - 14

ER -