Despite clinical and scientific advancements, heart failure is the major cause of morbidity and mortality worldwide. Both mitochondrial dysfunction and inflammation contribute to the development and progression of heart failure. Although inflammation is crucial to reparative healing following acute cardiomyocyte injury, chronic inflammation damages the heart, impairs function, and decreases cardiac output. Mitochondria, which comprise one third of cardiomyocyte volume, may prove a potential therapeutic target for heart failure. Known primarily for energy production, mitochondria are also involved in other processes including calcium homeostasis and the regulation of cellular apoptosis. Mitochondrial function is closely related to morphology, which alters through mitochondrial dynamics, thus ensuring that the energy needs of the cell are met. However, in heart failure, changes in substrate use lead to mitochondrial dysfunction and impaired myocyte function. This review discusses mitochondrial and cristae dynamics, including the role of the mitochondria contact site and cristae organizing system complex in mitochondrial ultrastructure changes. Additionally, this review covers the role of mitochondria-endoplasmic reticulum contact sites, mitochondrial communication via nanotunnels, and altered metabolite production during heart failure. We highlight these often-neglected factors and promising clinical mitochondrial targets for heart failure.

cardiovascular diseases, heart failure, hypertension, mitochondria, myocardium

.Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The global burden of cardiovascular diseases and risk: a compass for future health. J Am Coll Cardiol. ;:–. doi: ./j.jacc...

.Office of the Associate Director for Policy and Strategy. Health Topics: Heart Disease and Heart Attack. Centers for Disease Control and Prevention;

.Haddad F, Hunt S, Rosenthal D, Murphy D. Right ventricular function in cardiovascular disease, Part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. ;:–. doi: ./CIRCULATIONAHA..

.Fox KF, Cowie MR, Wood DA, Coats AJS, Gibbs JSR, Underwood SR, Turner RM, Poole-Wilson PA, Davies SW, Sutton GC. Coronary artery disease as the cause of incident heart failure in the population. Eur Heart J. ;:–. doi: ./euhj..

.Bauersachs R, Zeymer U, Brière J-B, Marre C, Bowrin K, Huelsebeck M. Burden of coronary artery disease and peripheral artery disease: a literature review. Cardiovasc Ther. ;:. doi: .//

.Brown JC, Gerhardt TE, Kwon E. Risk Factors for Coronary Artery Disease. StatPearls: StatPearls Publishing; . [

.Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. ;:e–e. doi: ./CIR.

.Golla MSG, Shams P. Heart Failure With Preserved Ejection Fraction (HFpEF). StatPearls, Treasure Island (FL): StatPearls Publishing; . [

.Kemp CD, Conte JV. The pathophysiology of heart failure. Cardiovasc Pathol. ;:–. doi: ./j.carpath...

.Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur J Heart Fail. ;:–. doi: ./ejhf.

.Rodgers JL, Jones J, Bolleddu SI, Vanthenapalli S, Rodgers LE, Shah K, Karia K, Panguluri SK. Cardiovascular risks associated with gender and aging. J Cardiovasc Dev Dis. ;:. doi: ./jcdd

.Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA. Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol. ;:–. doi: ./s---

.Elorza AA, Soffia JP. mtDNA heteroplasmy at the core of aging-associated heart failure. An integrative view of OXPHOS and mitochondrial life cycle in cardiac mitochondrial physiology. Front Cell Dev Biol. ;:. doi: ./fcell..

.Karamanlidis G, Bautista-Hernández V, Fynn-Thompson F, Nido PD, Tian R. Impaired mitochondrial biogenesis precedes heart failure in right ventricular hypertrophy in congenital heart disease. Circ Heart Fail. ;:–. doi: ./CIRCHEARTFAILURE..

.Karamanlidis G, Nascimben L, Couper G, Shekar P, Monte F, Tian R. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res. ;:–. doi: ./CIRCRESAHA..

.Liu M, Lv J, Pan Z, Wang D, Zhao L, Guo X. Mitochondrial dysfunction in heart failure and its therapeutic implications. Front Cardiovasc Med. ;

.Wu C, Zhang Z, Zhang W, Liu X. Mitochondrial dysfunction and mitochondrial therapies in heart failure. Pharmacol Res. ;:. doi: ./j.phrs..

.Bayeva M, Gheorghiade M, Ardehali H. Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol. ;:–. doi: ./j.jacc...

.Brown DA, Perry JB, Allen ME, Sabbah HN, Stauffer BL, Shaikh SR, Cleland JGF, Colucci WS, Butler J, Voors AA, et al. Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol. ;:–. doi: ./nrcardio..