{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:30:43Z","timestamp":1790955043446,"version":"4.1.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Heart Fail Rev"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Barth syndrome is a rare and potentially fatal X-linked disease characterized by cardiomyopathy, skeletal muscle weakness, growth delays, and cyclic neutropenia. Patients with Barth syndrome are prone to high risk of mortality in infancy and the development of cardiomyopathy with severe weakening of the immune system. Elamipretide is a water-soluble, aromatic-cationic, mitochondria-targeting tetrapeptide that readily penetrates and transiently localizes to the inner mitochondrial membrane. Therapy with elamipretide facilitates cell health by improving energy production and inhibiting excessive formation of reactive oxygen species, thus alleviating oxidative stress. Elamipretide crosses the outer membrane of the mitochondrion and becomes associated\u00a0with cardiolipin, a constituent phospholipid of the inner membrane. Elamipretide improves mitochondrial bioenergetics and morphology rapidly in induced pluripotent stem cells from patients with Barth syndrome and other genetically related diseases characterized by pediatric cardiomyopathy. Data with elamipretide across multiple models of disease are especially promising, with results from several studies supporting the use of elamipretide as potential therapy for patients with Barth syndrome, particularly where there is a confirmed diagnosis of cardiomyopathy. This review highlights the challenges and opportunities presented in treating Barth syndrome cardiomyopathy patients with elamipretide and addresses evidence supporting the durability of effect of elamipretide as a therapeutic agent for Barth syndrome, especially its likely durable effects on progression of cardiomyopathy following the cessation of drug treatment and the capability of elamipretide to structurally reverse remodel the failing left ventricle at the global, cellular, and molecular level in a gradual manner through specific targeting of the mitochondrial inner membrane.<\/jats:p>","DOI":"10.1007\/s10741-021-10177-8","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T03:34:29Z","timestamp":1633750469000},"page":"1911-1923","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Elamipretide for Barth syndrome cardiomyopathy: gradual rebuilding of a failed power grid"],"prefix":"10.1007","volume":"27","author":[{"given":"Hani N.","family":"Sabbah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"10177_CR1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2147\/TACG.S171481","volume":"12","author":"J Finsterer","year":"2019","unstructured":"Finsterer J (2019) Barth syndrome: mechanisms and management. Appl Clin Genet 12:95\u2013106. https:\/\/doi.org\/10.2147\/TACG.S171481","journal-title":"Appl Clin Genet"},{"key":"10177_CR2","doi-asserted-by":"publisher","unstructured":"Bissler JJ, Tsoras M, Goring HH, Hug P, Chuck G, Tombragel E, McGraw C, Schlotman J, Ralston MA, Hug G (2002) Infantile dilated X-linked cardiomyopathy, G4.5 mutations, altered lipids, and ultrastructural malformations of mitochondria in heart, liver, and skeletal muscle. Lab Invest 82(3):335\u2013344. https:\/\/doi.org\/10.1038\/labinvest.3780427","DOI":"10.1038\/labinvest.3780427"},{"issue":"51","key":"10177_CR3","doi-asserted-by":"publisher","first-page":"51380","DOI":"10.1074\/jbc.M307382200","volume":"278","author":"Y Xu","year":"2003","unstructured":"Xu Y, Kelley RI, Blanck TJ, Schlame M (2003) Remodeling of cardiolipin by phospholipid transacylation. J Biol Chem 278(51):51380\u201351385. https:\/\/doi.org\/10.1074\/jbc.M307382200","journal-title":"J Biol Chem"},{"key":"10177_CR4","doi-asserted-by":"publisher","unstructured":"Sabbah HN (2020) Barth syndrome cardiomyopathy: targeting the mitochondria with elamipretide. Heart Fail Rev 26(2):237\u2013253. https:\/\/doi.org\/10.1007\/s10741-020-10031-3.","DOI":"10.1007\/s10741-020-10031-3"},{"key":"10177_CR5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1750-1172-8-23","volume":"8","author":"SL Clarke","year":"2013","unstructured":"Clarke SL, Bowron A, Gonzalez IL, Groves SJ, Newbury-Ecob R, Clayton N, Martin RP, Tsai-Goodman B, Garratt V, Ashworth M, Bowen VM, McCurdy KR, Damin MK, Spencer CT, Toth MJ, Kelley RI, Steward CG (2013) Barth syndrome. Orphanet J Rare Dis 8:23. https:\/\/doi.org\/10.1186\/1750-1172-8-23","journal-title":"Orphanet J Rare Dis"},{"issue":"2","key":"10177_CR6","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1074\/jbc.M110.171439","volume":"286","author":"D Acehan","year":"2011","unstructured":"Acehan D, Vaz F, Houtkooper RH, James J, Moore V, Tokunaga C, Kulik W, Wansapura J, Toth MJ, Strauss A, Khuchua Z (2011) Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem 286(2):899\u2013908. https:\/\/doi.org\/10.1074\/jbc.M110.171439","journal-title":"J Biol Chem"},{"issue":"21","key":"10177_CR7","doi-asserted-by":"publisher","first-page":"17589","DOI":"10.1074\/jbc.M111.330167","volume":"287","author":"AS Joshi","year":"2012","unstructured":"Joshi AS, Thompson MN, Fei N, Huttermann M, Greenberg ML (2012) Cardiolipin and mitochondrial phosphatidylathanolamine have overlapping in mitochondrial fusion in Saccharomices cerevisiae. J Biol Chem 287(21):17589\u201317597. https:\/\/doi.org\/10.1074\/jbc.M111.330167","journal-title":"J Biol Chem"},{"issue":"6","key":"10177_CR8","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.003118","volume":"5","author":"A Eirin","year":"2016","unstructured":"Eirin A, Ebrahimi B, Kwon SH, Fiala JA, Williams BJ, Woollard JR, He Q, Gupta RC, Sabbah HN, Prakash YS, Textor SC, Lerman A, Lerman LO (2016) Restoration of mitochondrial cardiolipin attenuates cardiac damage in swine renovascular hypertension. J Am Heart Assoc 5(6):e003118. https:\/\/doi.org\/10.1161\/JAHA.115.003118","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"10177_CR9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002206","volume":"9","author":"HN Sabbah","year":"2016","unstructured":"Sabbah HN, Gupta RC, Kohli S, Wang M, Hachem S, Zhang K (2016) Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circ Heart Fail 9(2):e002206. https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.115.002206","journal-title":"Circ Heart Fail"},{"key":"10177_CR10","doi-asserted-by":"publisher","unstructured":"Braun JL, Hamstra SI, Messner HN, Fajardo VA (2019) SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice. Phys Rep 7(16):e14215. https:\/\/doi.org\/10.14814\/phy2.14215","DOI":"10.14814\/phy2.14215"},{"key":"10177_CR11","first-page":"1","volume-title":"Harrison's principles of internal medicine","author":"NK Lakdawala","year":"2015","unstructured":"Lakdawala NK, Stevenson LW, Loscalzo J (2015) Cardiomyopathy and myocarditis. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J (eds) Harrison\u2019s principles of internal medicine, 19th edn. McGraw-Hill, New York, pp 1\u201337","edition":"19"},{"issue":"5","key":"10177_CR12","doi-asserted-by":"publisher","first-page":"H2122","DOI":"10.1152\/ajpheart.00479.2010","volume":"301","author":"CT Spencer","year":"2011","unstructured":"Spencer CT, Byrne BJ, Bryant RM, Margossian R, Maisenbacher M, Breitenger P, Benni PB, Redfearn S, Marcus E, Cade WT (2011) Impaired cardiac reserve and severely diminished skeletal muscle O2 utilization mediate exercise intolerance in Barth syndrome. Am J Physiol Heart Circ Physiol 301(5):H2122-2129. https:\/\/doi.org\/10.1152\/ajpheart.00479.2010","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"4","key":"10177_CR13","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1093\/cvr\/cvx014","volume":"113","author":"J Dudek","year":"2017","unstructured":"Dudek J, Maack C (2017) Barth syndrome cardiomyopathy. Cardiovasc Res 113(4):399\u2013410. https:\/\/doi.org\/10.1093\/cvr\/cvx014","journal-title":"Cardiovasc Res"},{"issue":"2","key":"10177_CR14","doi-asserted-by":"publisher","first-page":"e337","DOI":"10.1542\/peds.2005-2667","volume":"118","author":"CT Spencer","year":"2006","unstructured":"Spencer CT, Bryant RM, Day J, Gonzalez IL, Colan SD, Thompson WR, Berthy J, Redfearn SP, Byrne BJ (2006) Cardiac and clinical phenotype in Barth syndrome. Pediatrics 118(2):e337-346. https:\/\/doi.org\/10.1542\/peds.2005-2667","journal-title":"Pediatrics"},{"issue":"9716","key":"10177_CR15","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/S0140-6736(09)62023-7","volume":"375","author":"JL Jefferies","year":"2010","unstructured":"Jefferies JL, Towbin JA (2010) Dilated cardiomyopathy. Lancet 375(9716):752\u2013762. https:\/\/doi.org\/10.1016\/S0140-6736(09)62023-7","journal-title":"Lancet"},{"issue":"3","key":"10177_CR16","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41436-020-01006-8","volume":"23","author":"RW Thompson","year":"2021","unstructured":"Thompson RW, Hornby B, Manuel R, Bradley E, Laux J, Carr J, Vernon HJ (2021) A phase 2\/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med 23(3):471\u2013478. https:\/\/doi.org\/10.1038\/s41436-020-01006-8","journal-title":"Genet Med"},{"issue":"3","key":"10177_CR17","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/ajmg.1320450309","volume":"45","author":"LC Ades","year":"1993","unstructured":"Ades LC, Gedeon AK, Wilson MJ, Latham M, Partington MW, Mulley JC, Nelson J, Lui K, Sillence DO (1993) Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28. Am J Med Genet 45(3):327\u2013334. https:\/\/doi.org\/10.1002\/ajmg.1320450309","journal-title":"Am J Med Genet"},{"issue":"4","key":"10177_CR18","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1086\/514879","volume":"61","author":"SB Bleyl","year":"1997","unstructured":"Bleyl SB, Mumford BR, Thompson V, Carey JC, Pysher TJ, Chin TK, Ward K (1997) Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet 61(4):868\u2013872. https:\/\/doi.org\/10.1086\/514879","journal-title":"Am J Hum Genet"},{"issue":"3","key":"10177_CR19","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/ajmg.c.31372","volume":"163C","author":"JL Jefferies","year":"2013","unstructured":"Jefferies JL (2013) Barth syndrome. Am J Med Genet C Semin Med Genet 163C(3):198\u2013205. https:\/\/doi.org\/10.1002\/ajmg.c.31372","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"6868","key":"10177_CR20","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/415227a","volume":"415","author":"JA Towbin","year":"2002","unstructured":"Towbin JA, Bowles NE (2002) The failing heart. Nature 415(6868):227\u2013233. https:\/\/doi.org\/10.1038\/415227a","journal-title":"Nature"},{"issue":"21","key":"10177_CR21","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1161\/01.CIR.0000100664.10777.B8","volume":"108","author":"RH Pignatelli","year":"2003","unstructured":"Pignatelli RH, McMahon CJ, Dreyer WJ, Denfield SW, Price J, Belmont JW, Craigen WJ, Wu J, El Said H, Bezold LI, Clunie S, Fernbach S, Bowles NE, Towbin JA (2003) Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 108(21):2672\u20132678. https:\/\/doi.org\/10.1161\/01.CIR.0000100664.10777.B8","journal-title":"Circulation"},{"issue":"22","key":"10177_CR22","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1161\/CIRCULATIONAHA.107.746164","volume":"117","author":"S Klaassen","year":"2008","unstructured":"Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hurlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L (2008) Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation 117(22):2893\u20132901. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.107.746164","journal-title":"Circulation"},{"issue":"2","key":"10177_CR23","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/cvr\/cvq231","volume":"88","author":"DA Brown","year":"2010","unstructured":"Brown DA, O\u2019Rourke B (2010) Cardiac mitochondria and arrhythmias. Cardiovasc Res 88(2):241\u2013249. https:\/\/doi.org\/10.1093\/cvr\/cvq231","journal-title":"Cardiovasc Res"},{"issue":"22","key":"10177_CR24","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1161\/CIRCULATIONAHA.113.002511","volume":"127","author":"ST Brescia","year":"2013","unstructured":"Brescia ST, Rossano JW, Pignatelli R, Jefferies JL, Price JF, Decker JA, Denfield SW, Dreyer WJ, Smith O, Towbin JA, Kim JJ (2013) Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center. Circulation 127(22):2202\u20132208. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.113.002511","journal-title":"Circulation"},{"key":"10177_CR25","doi-asserted-by":"publisher","unstructured":"Pouleur H (1990) Diastolic dysfunction and myocardial energetics. Euro Heart J 11 Suppl C:30\u201334. https:\/\/doi.org\/10.1093\/eurheartj\/11.suppl_c.30","DOI":"10.1093\/eurheartj\/11.suppl_c.30"},{"issue":"4","key":"10177_CR26","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","volume":"14","author":"DA Brown","year":"2017","unstructured":"Brown DA, Perry JB, Allen ME, Sabbah HN, Stauffer BL, Shaikh SR, Cleland JG, Colucci WS, Butler J, Voors AA, Anker SD, Pitt B, Pieske B, Filippatos G, Greene SJ, Gheorghiade M (2017) Expert consensus document: mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol 14(4):238\u2013250. https:\/\/doi.org\/10.1038\/nrcardio.2016.203","journal-title":"Nat Rev Cardiol"},{"key":"10177_CR27","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s10557-018-6805-y","volume":"32","author":"HN Sabbah","year":"2018","unstructured":"Sabbah HN, Gupta RC, Singh-Gupta V, Zhang K (2018) Abnormalities of mitochondrial dynamics in the failing heart: normalization following long-term therapy with elamipretide. Cardiovasc Drugs Ther 32:319\u2013328. https:\/\/doi.org\/10.1007\/s10557-018-6805-y","journal-title":"Cardiovasc Drugs Ther"},{"issue":"1","key":"10177_CR28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jacbts.2019.07.009","volume":"5","author":"HN Sabbah","year":"2020","unstructured":"Sabbah HN (2020) Targeting the mitochondria in heart failure: a translational perspective. J Am Coll Cardiol Basic Trans Sci 5(1):88\u2013106. https:\/\/doi.org\/10.1016\/j.jacbts.2019.07.009","journal-title":"J Am Coll Cardiol Basic Trans Sci"},{"issue":"6","key":"10177_CR29","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.coph.2009.09.002","volume":"9","author":"DL Johannsen","year":"2009","unstructured":"Johannsen DL, Ravussin E (2009) The role of mitochondria in health and disease. Curr Opin Pharmacol 9(6):780\u2013786. https:\/\/doi.org\/10.1016\/j.coph.2009.09.002","journal-title":"Curr Opin Pharmacol"},{"issue":"8","key":"10177_CR30","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1161\/CIRCRESAHA.110.220673","volume":"107","author":"M Liu","year":"2010","unstructured":"Liu M, Liu H, Dudley SC (2010) Reactive oxygen species originating from mitochondria regulate the cardiac sodium channel. Circ Res 107(8):967\u2013974. https:\/\/doi.org\/10.1161\/CIRCRESAHA.110.220673","journal-title":"Circ Res"},{"issue":"5","key":"10177_CR31","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.molmed.2014.01.005","volume":"20","author":"N Raimundo","year":"2014","unstructured":"Raimundo N (2014) Mitochondrial pathology: stress signals from the energy factory. Trends Mol Med 20(5):282\u2013292. https:\/\/doi.org\/10.1016\/j.molmed.2014.01.005","journal-title":"Trends Mol Med"},{"issue":"3","key":"10177_CR32","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1161\/01.res.56.3.377","volume":"56","author":"J Schaper","year":"1985","unstructured":"Schaper J, Meiser E, Stammler G (1985) Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts. Circ Res 56(3):377\u2013391. https:\/\/doi.org\/10.1161\/01.res.56.3.377","journal-title":"Circ Res"},{"issue":"7","key":"10177_CR33","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/0022-2828(92)93381-s","volume":"24","author":"E Barth","year":"1992","unstructured":"Barth E, Stammler G, Speiser B, Schaper J (1992) Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. J Mol Cell Cardiol 24(7):669\u2013681. https:\/\/doi.org\/10.1016\/0022-2828(92)93381-s","journal-title":"J Mol Cell Cardiol"},{"issue":"9","key":"10177_CR34","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1172\/JCI31060","volume":"117","author":"H Nakayama","year":"2007","unstructured":"Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, Jaleel N, Chua BH, Hewett TE, Robbins J, Houser SR, Molkentin JD (2007) Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest 117(9):2431\u20132444. https:\/\/doi.org\/10.1172\/JCI31060","journal-title":"J Clin Invest"},{"issue":"5876","key":"10177_CR35","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1126\/science.1156995","volume":"320","author":"C Dostert","year":"2008","unstructured":"Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320(5876):674\u2013677. https:\/\/doi.org\/10.1126\/science.1156995","journal-title":"Science"},{"issue":"3","key":"10177_CR36","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/ni.1980","volume":"12","author":"K Nakahira","year":"2011","unstructured":"Nakahira K, Haspel JA, Rathinam VAK, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM (2011) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12(3):222\u2013230. https:\/\/doi.org\/10.1038\/ni.1980","journal-title":"Nat Immunol"},{"issue":"7329","key":"10177_CR37","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","volume":"469","author":"R Zhou","year":"2011","unstructured":"Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329):221\u2013225. https:\/\/doi.org\/10.1038\/nature09663","journal-title":"Nature"},{"issue":"7397","key":"10177_CR38","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nature10992","volume":"485","author":"T Oka","year":"2012","unstructured":"Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K (2012) Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485(7397):251\u2013255. https:\/\/doi.org\/10.1038\/nature10992","journal-title":"Nature"},{"issue":"5","key":"10177_CR39","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1194\/jlr.M034728","volume":"54","author":"MA Kiebish","year":"2013","unstructured":"Kiebish MA, Yang K, Liu X, Mancuso DJ, Guan S, Zhao Z, Sims HF, Cerqua R, Cade WT, Han X, Gross RW (2013) Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome. J Lipid Res 54(5):1312\u20131325. https:\/\/doi.org\/10.1194\/jlr.M034728","journal-title":"J Lipid Res"},{"issue":"2","key":"10177_CR40","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/BF01799418","volume":"19","author":"P Barth","year":"1996","unstructured":"Barth P, Van den Bogert C, Bolhuis P, Scholte HR, van Gennip AH, Schutgens RB, Ketel AG (1996) X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): respiratory-chain abnormalities in cultured fibroblasts. J Inherit Metab Dis 19(2):157\u2013160. https:\/\/doi.org\/10.1007\/BF01799418","journal-title":"J Inherit Metab Dis"},{"issue":"6","key":"10177_CR41","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/labinvest.3700274","volume":"85","author":"Y Xu","year":"2005","unstructured":"Xu Y, Sutachan JJ, Plesken H, Kelley RI, Schlame M (2005) Characterization of lymphoblast mitochondria from patients with Barth syndrome. Lab Invest 85(6):823\u2013830. https:\/\/doi.org\/10.1038\/labinvest.3700274","journal-title":"Lab Invest"},{"issue":"1","key":"10177_CR42","doi-asserted-by":"publisher","first-page":"H210","DOI":"10.1152\/ajpheart.00098.2010","volume":"299","author":"Q He","year":"2010","unstructured":"He Q (2010) Tafazzin knockdown causes hypertrophy of neonatal ventricular myocytes. Am J Physiol 299(1):H210-216. https:\/\/doi.org\/10.1152\/ajpheart.00098.2010","journal-title":"Am J Physiol"},{"issue":"9","key":"10177_CR43","doi-asserted-by":"publisher","first-page":"H1332","DOI":"10.1152\/ajpheart.00084.2013","volume":"305","author":"Q He","year":"2013","unstructured":"He Q, Wang M, Harris N, Han X (2013) Tafazzin knockdown interrupts cell cycle progression in cultured neonatal ventricular fibroblasts. Am J Physiol 305(9):H1332-1343. https:\/\/doi.org\/10.1152\/ajpheart.00084.2013","journal-title":"Am J Physiol"},{"issue":"12","key":"10177_CR44","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.scr.2013.05.005","volume":"11","author":"J Dudek","year":"2013","unstructured":"Dudek J, Cheng I-F, Balleininger M, Vaz FM, Streckfuss-Bomeke K, Hubscher D, Vukotic M, Wanders RJ, Rehling P, Guan K (2013) Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome. Stem Cell Res 11(12):806\u2013819. https:\/\/doi.org\/10.1016\/j.scr.2013.05.005","journal-title":"Stem Cell Res"},{"key":"10177_CR45","doi-asserted-by":"publisher","unstructured":"Dudek J, Cheng I-F, Chowdhury A, Vaz FM, Streckfuss-Bomeke K, Hubscher D, Vukotic M, Wanders RJ, Rehling P, Guan K (2015) Cardiac-specific succinate dehydrogenase deficiency in Barth syndrome. EMBO Mol Med 8(2):139\u2013154. https:\/\/doi.org\/10.15252\/emmm.201505644","DOI":"10.15252\/emmm.201505644"},{"key":"10177_CR46","doi-asserted-by":"publisher","unstructured":"Imai-Okazaki A, Kishita Y, Kohda M, Yatsuka Y, Hirata T, Mizuno Y, Harashima H, Hirono K, Ichida F, Noguchi A, Yoshida M, Tokorodani C, Nishiuchi R, Takeda A, Nakaya A, Sakata Y, Murayama K, Ohtake A, Okazaki Y (2018) Barth syndrome: different approaches to diagnosis. J Pediatr 193:256\u2013260. https:\/\/doi.org\/10.1016\/j.jpeds.2017.09.075","DOI":"10.1016\/j.jpeds.2017.09.075"},{"key":"10177_CR47","doi-asserted-by":"publisher","unstructured":"Adwani SS, Whitehead BF, Rees PG, Morris A, Turnball DM, Elliott MJ, de Leval MR. Heart transplantation for Barth syndrome (1997) Pediatr Cardiol 18(2):143\u2013145. https:\/\/doi.org\/10.1007\/s002469900135","DOI":"10.1007\/s002469900135"},{"key":"10177_CR48","doi-asserted-by":"publisher","unstructured":"Mangat J, Lunnon-Wood T, Rees P, Elliott M, Burch M (2007) Successful cardiac transplantation in Barth syndrome: single-centre experience of four patients. Pediatr Transplant 11(3):327\u2013331. https:\/\/doi.org\/10.1111\/j.1399-3046.2006.00629.x","DOI":"10.1111\/j.1399-3046.2006.00629.x"},{"key":"10177_CR49","doi-asserted-by":"publisher","unstructured":"Roberts AE, Nixon C, Steward CG, Gauvreau K, Maisenbacher M, Fletcher M, Geva J, Byrne BJ, Spencer CT (2012 The Barth Syndrome Registry: distinguishing disease characteristics and growth data from a longitudinal study. Am J Med Genet A 158A(11):2726\u20132732. https:\/\/doi.org\/10.1002\/ajmg.a.35609","DOI":"10.1002\/ajmg.a.35609"},{"key":"10177_CR50","doi-asserted-by":"publisher","unstructured":"Kang SL, Forsey J, Dudley D, Steward CG, Tsai-Goodman B (2016) Clinical characteristics and outcomes of cardiomyopathy in Barth syndrome: the UK experience. Pediatr Cardiol 37(1):167\u2013176. https:\/\/doi.org\/10.1007\/s00246-015-1260-z","DOI":"10.1007\/s00246-015-1260-z"},{"key":"10177_CR51","doi-asserted-by":"publisher","unstructured":"Hanke SP, Gardner AB, Lombardi JP, Manning PB, Nelson DP, Towbin JA, Jefferies JL, Lorts A (2012) Left ventricular noncompaction cardiomyopathy in Barth syndrome: an example of an undulating cardiac phenotype necessitating mechanical circulatory support as a bridge to transplantation. Pediatr Cardiol 33(8):1430\u20131434. https:\/\/doi.org\/10.1007\/s00246-012-0258-z","DOI":"10.1007\/s00246-012-0258-z"},{"issue":"9","key":"10177_CR52","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1089\/ars.2009.2445","volume":"11","author":"L Yang","year":"2009","unstructured":"Yang L, Zhao K, Calingasan NY, Luo G, Szeto HH, Beal ME (2009) Mitochondria targeted peptides protect against 1-methy1-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Antioxid Redox Signal 11(9):2095\u20132104. https:\/\/doi.org\/10.1089\/ars.2009.2445","journal-title":"Antioxid Redox Signal"},{"issue":"6","key":"10177_CR53","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1681\/ASN.2010080808","volume":"22","author":"HH Szeto","year":"2011","unstructured":"Szeto HH, Liu S, Soong Y, Wu D, Darrah SF, Cheng FY, Zhao Z, Ganger M, Tow CY, Seshan SV (2011) Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. J Am Soc Nephrol 22(6):1041\u20131052. https:\/\/doi.org\/10.1681\/ASN.2010080808","journal-title":"J Am Soc Nephrol"},{"issue":"5","key":"10177_CR54","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1161\/CIRCHEARTFAILURE.113.000406","volume":"6","author":"D-F Dai","year":"2013","unstructured":"Dai D-F, Hsieh EJ, Chen T, Menendez LG, Basisty NB, Tsai L, Beyer RP, Crispin DA, Shulman NJ, Szeto HH, Tian R, MacCoss MJ, Rabinovitch PS (2013) Global proteomics and pathway analysis of pressure overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Circ Heart Fail 6(5):1067\u20131076. https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.113.000406","journal-title":"Circ Heart Fail"},{"issue":"4","key":"10177_CR55","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1152\/japplphysiol.00471.2013","volume":"115","author":"EE Talbert","year":"1985","unstructured":"Talbert EE, Smuder AJ, Min K, Kwon OS, Szeto HH (1985) Powers SK (2013) Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant. J Appl Physiol 115(4):529\u2013538. https:\/\/doi.org\/10.1152\/japplphysiol.00471.2013","journal-title":"J Appl Physiol"},{"issue":"1","key":"10177_CR56","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1177\/1074248413508003","volume":"19","author":"DA Brown","year":"2014","unstructured":"Brown DA, Hale SL, Baines CP, del Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Shaikh SR, Fisher-Wellman KH, Neufer PD (2014) Kloner RA (2014) Reduction of early reperfusion injury with the mitochondria-targeting peptide Bendavia. J Cardiovasc Pharmacol Ther 19(1):121\u2013132. https:\/\/doi.org\/10.1177\/1074248413508003","journal-title":"J Cardiovasc Pharmacol Ther"},{"issue":"2","key":"10177_CR57","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/ehf2.12408","volume":"6","author":"HN Sabbah","year":"2019","unstructured":"Sabbah HN, Gupta RC, Singh-Gupta V, Zhang K (2019) Effects of elamipretide on skeletal muscle in dogs with experimentally induced heart failure. ESC Heart Fail 6(2):328\u2013335. https:\/\/doi.org\/10.1002\/ehf2.12408","journal-title":"ESC Heart Fail"},{"issue":"1","key":"10177_CR58","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s42003-020-1101-3","volume":"3","author":"ME Allen","year":"2020","unstructured":"Allen ME, Pennington ER, Perry JB, Dadoo S, Makrecka-Kuka M, Dambrova M, Moukdar F, Patel HD, Han X, Kidd GK, Benson EK, Raisch TB, Poelzing S, Brown DA, Shaikh SR (2020) The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats. Nat Commun Biol 3(1):389. https:\/\/doi.org\/10.1038\/s42003-020-1101-3","journal-title":"Nat Commun Biol"},{"key":"10177_CR59","doi-asserted-by":"publisher","unstructured":"Mitchell W, Ng EA, Tamucci XJD, Boyd KJ, Sathappa M, Coscia A, Pan M, Han X, Eddy NA, May ER, Szeto HH, Alder NN (2020) The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem 295(21):7452\u20137469. https:\/\/doi.org\/10.1074\/jbc.RA119.012094","DOI":"10.1074\/jbc.RA119.012094"},{"issue":"6","key":"10177_CR60","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/nm.3545","volume":"20","author":"G Wang","year":"2014","unstructured":"Wang G, McCain ML, Yang L, He A, Pasqualini FS, Agarwal A, Yuan H, Jiang D, Zhang D, Zangi L, Geva J, Roberts AE, Ma Q, Ding J, Chen J, Wang DZ, Li K, Wang J, Wanders RJ, Kulik W, Vaz FM, Laflamme MA, Murry CE, Chien KR, Kelley RI, Church GM, Parker KK, Pu WT (2014) Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med 20(6):616\u2013623. https:\/\/doi.org\/10.1038\/nm.3545","journal-title":"Nat Med"},{"issue":"4","key":"10177_CR61","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.cjca.2019.09.021","volume":"36","author":"L Rohani","year":"2020","unstructured":"Rohani L, Machiraju P, Sabouny R, Meng G, Liu S, Zhao T, Iqbal F, Wang X, Ravandi A, Wu JC, Khan A, Shutt T, Rancourt D, Greenway SC (2020) Reversible mitochondrial fragmentation in iPSC-derived cardiomyocytes from children with DCMA, a mitochondrial cardiomyopathy. Can J Cardiol 36(4):554\u2013563. https:\/\/doi.org\/10.1016\/j.cjca.2019.09.021","journal-title":"Can J Cardiol"},{"issue":"20","key":"10177_CR62","doi-asserted-by":"publisher","first-page":"20235580","DOI":"10.1101\/2020.11.20.20235580","volume":"11","author":"PJ Oates","year":"2020","unstructured":"Oates PJ, Brown DA, Vernon HJ, Gangoiti JA, Barshop BA (2020) Metabolomic biomarkers from patients with Barth syndrome treated with elamipretide: insights from the TAZPOWER study. MedRxiv 11(20):20235580. https:\/\/doi.org\/10.1101\/2020.11.20.20235580","journal-title":"MedRxiv"},{"issue":"3","key":"10177_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101005","volume":"297","author":"AF Anzmann","year":"2021","unstructured":"Anzmann AF, Sniezek OL, Pado A, Busa V, Vaz FM, Kreimer SD, DeVine LR, Cole RN, Le A, Kirsch BJ, Claypool SM, Vernon HJ (2021) Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by cardiolipin-interacting small molecules. J Biol Chem 297(3):101005. https:\/\/doi.org\/10.1016\/j.jbc.2021.101005","journal-title":"J Biol Chem"},{"key":"10177_CR64","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55513","volume":"9","author":"YA Chiao","year":"2020","unstructured":"Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P (2020) Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife 9:e55513. https:\/\/doi.org\/10.7554\/eLife.55513","journal-title":"Elife"},{"issue":"6","key":"10177_CR65","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1161\/01.cir.89.6.2852","volume":"89","author":"HN Sabbah","year":"1994","unstructured":"Sabbah HN, Shimoyama H, Kono T, Gupta RC, Sharov VG, Scicli G, Levine TB, Goldstein S (1994) Effects of long-term monotherapy with enalapril, metoprolol and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. Circulation 89(6):2852\u20132859. https:\/\/doi.org\/10.1161\/01.cir.89.6.2852","journal-title":"Circulation"},{"issue":"8","key":"10177_CR66","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1172\/JCI119360","volume":"99","author":"YH Liu","year":"1997","unstructured":"Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA (1997) Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure: role of kinins and angiotensin II type 2 receptors. J Clin Invest 99(8):1926\u20131935. https:\/\/doi.org\/10.1172\/JCI119360","journal-title":"J Clin Invest"},{"issue":"4","key":"10177_CR67","doi-asserted-by":"publisher","first-page":"H1385","DOI":"10.1152\/ajpheart.1999.276.4.H1385","volume":"276","author":"M Tanimura","year":"1999","unstructured":"Tanimura M, Sharov VG, Shimoyama H, Mishima T, Levine TB, Goldstein S, Sabbah HN (1999) Effects of AT1 receptor blockade on the progression of left ventricular dysfunction in dogs with heart failure. Am J Physiol 276(4):H1385-1392. https:\/\/doi.org\/10.1152\/ajpheart.1999.276.4.H1385","journal-title":"Am J Physiol"},{"issue":"4","key":"10177_CR68","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1159\/000159123","volume":"112","author":"V Zaca","year":"2009","unstructured":"Zaca V, Rastogi S, Mishra S, Wang M, Sharov VG, Gupta RC, Goldstein S, Sabbah HN (2009) Atenolol is inferior to metoprolol in improving left ventricular function and preventing ventricular remodeling in dogs with heart failure. Cardiology 112(4):294\u2013302. https:\/\/doi.org\/10.1159\/000159123","journal-title":"Cardiology"},{"issue":"1","key":"10177_CR69","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/cvr\/cvn184","volume":"80","author":"MG Rosca","year":"2008","unstructured":"Rosca MG, Vazquez EJ, Kerner J, Parland W, Chandler MP, Stanley W, Sabbah HN, Hoppel CL (2008) Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation. Cardiovasc Res 80(1):30\u201339. https:\/\/doi.org\/10.1093\/cvr\/cvn184","journal-title":"Cardiovasc Res"},{"issue":"6","key":"10177_CR70","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1083\/jcb.200906098","volume":"186","author":"RM DeVay","year":"2009","unstructured":"DeVay RM, Dominguez-Ramirez L, Lackner LL, Hoppins S, Stahlberg H, Nunnari J (2009) Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. J Cell Biol 186(6):793\u2013803. https:\/\/doi.org\/10.1083\/jcb.200906098","journal-title":"J Cell Biol"},{"issue":"8","key":"10177_CR71","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1681\/ASN.2012121216","volume":"24","author":"AV Birk","year":"2013","unstructured":"Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH (2013) The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol 24(8):1250\u20131261. https:\/\/doi.org\/10.1681\/ASN.2012121216","journal-title":"J Am Soc Nephrol"},{"key":"10177_CR72","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.bbabio.2015.03.007","volume":"6\u20137","author":"LA Luevano-Martinez","year":"1847","unstructured":"Luevano-Martinez LA, Forni MF (1847) Tiago dios Santios V, Souza-Pinto NC, Kowaltowski AJ (2015) Cardiolipin is a key determinant for mtDNA stability and segregation during mitochondrial stress. Biochim Biophys Acta 6\u20137:587\u2013598. https:\/\/doi.org\/10.1016\/j.bbabio.2015.03.007","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"10177_CR73","first-page":"141","volume":"148","author":"VG Sharov","year":"1996","unstructured":"Sharov VG, Sabbah HN, Shimoyama H, Goussev AV, Lesch M, Goldstein S (1996) Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 148(1):141\u2013149","journal-title":"Am J Pathol"},{"issue":"5","key":"10177_CR74","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1681\/ASN.2016070761","volume":"28","author":"HH Szeto","year":"2017","unstructured":"Szeto HH, Liu S, Soong Y, Seshan SV, Cohen-Gould L, Manichev V, Feldman LC, Gustafsson T (2017) Mitochondria protection after acute ischemia prevents prolonged upregulation of IL-1\u03b2 and IL-18 and arrests CKD. J Am Soc Nephrol 28(5):1437\u20131449. https:\/\/doi.org\/10.1681\/ASN.2016070761","journal-title":"J Am Soc Nephrol"}],"container-title":["Heart Failure Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10741-021-10177-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10741-021-10177-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10741-021-10177-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T07:28:31Z","timestamp":1660807711000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10741-021-10177-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":74,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10177"],"URL":"https:\/\/doi.org\/10.1007\/s10741-021-10177-8","relation":{},"ISSN":["1382-4147","1573-7322"],"issn-type":[{"value":"1382-4147","type":"print"},{"value":"1573-7322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]},"assertion":[{"value":"30 September 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Sabbah is a consultant to Stealth Biotherapeutics, Inc. and member of their Scientific Advisory Board. Dr. Sabbah also serves as a consultant to Bayer AG and Arena Pharmaceuticals, Inc. and has received research grant funding from Bayer AG, Arena Pharmaceuticals, Novartis Corp., and Bristol-Myers Squibb Company.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}