Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy

References

• Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249–1254. DOI:10.1016/j.jacc.2015.01.019
   PubMed Web of Science ®Google Scholar
• Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60(8):705–715.
   PubMed Web of Science ®Google Scholar
• Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20(1):1–8.
   PubMedGoogle Scholar
• Braunwald E, Lambrew CT, Rockoff SD, et al. Idiopathic hypertrophic subaortic stenosis: i. A description of the disease based upon an analysis of 64 patients. Circulation. 1964;29(SUPPL 5s4):3–119. DOI:10.1161/01.CIR.29.5S4.IV-3
   Google Scholar
• Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e558–e631.
   PubMed Web of Science ®Google Scholar
• Maron BJ. Clinical course and management of hypertrophic cardiomyopathy. N Engl J Med. 2018;379(7):655–668.
   PubMed Web of Science ®Google Scholar
• Geske JB, Ommen SR, Gersh BJ. Hypertrophic cardiomyopathy: clinical update. JACC Heart Fail. 2018;6(5):364–375.
   PubMed Web of Science ®Google Scholar
• Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003;348(4):295–303. DOI:10.1056/NEJMoa021332
   PubMed Web of Science ®Google Scholar
• Morrow AG, Lambrew CT, Braunwald E. Idiopathic hypertrophic subaortic stenosis: iI. operative treatment and the results of pre- and postoperative hemodynamic evaluations. Circulation. 1964;29(suppl 5s4):120–151.
   Google Scholar
• Maron BJ, Dearani JA, Ommen SR, et al. Low operative mortality achieved with surgical septal myectomy: role of dedicated hypertrophic cardiomyopathy centers in the management of dynamic subaortic obstruction. J Am Coll Cardiol. 2015;66(11):1307–1308. DOI:10.1016/j.jacc.2015.06.1333
   PubMedGoogle Scholar
• Osman M, Kheiri B, Osman K, et al. Alcohol septal ablation vs myectomy for symptomatic hypertrophic obstructive cardiomyopathy: systematic review and meta-analysis. Clin Cardiol. 2019;42(1):190–197. DOI:10.1002/clc.23113
   PubMed Web of Science ®Google Scholar
• Spoladore R, Maron MS, D’Amato R, et al. Pharmacological treatment options for hypertrophic cardiomyopathy: high time for evidence. Eur Heart J. 2012;33(14):1724–1733. DOI:10.1093/eurheartj/ehs150
   PubMed Web of Science ®Google Scholar
• Palandri C, Santini L, Argirò A, et al. Pharmacological management of hypertrophic cardiomyopathy: from bench to bedside. Drugs. 2022;82(8):889–912. DOI:10.1007/s40265-022-01728-w
   PubMed Web of Science ®Google Scholar
• Argirò A, Zampieri M, Berteotti M, et al. Emerging medical treatment for hypertrophic cardiomyopathy. J Clin Med. 2021;10(5):951. DOI:10.3390/jcm10050951
   PubMed Web of Science ®Google Scholar
• Gregor P, Čurila K. Medical treatment of hypertrophic cardiomyopathy - What do we know about it today? Cor Vasa. 2015;57(3):e219–e224.
   Google Scholar
• Dybro AM, Rasmussen TB, Nielsen RR, et al. Effects of metoprolol on exercise hemodynamics in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2022;79(16):1565–1575. DOI:10.1016/j.jacc.2022.02.024
   PubMed Web of Science ®Google Scholar
• Ammirati E, Contri R, Coppini R, et al. Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives. Eur J Heart Fail. 2016;18(9):1106–1118. DOI:10.1002/ejhf.541
   PubMed Web of Science ®Google Scholar
• Monda E, Lioncino M, Palmiero G, et al. Bisoprolol for treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy. The BASIC (bisoprolol as therapy in hypertrophic cardiomyopathy) study. Int J Cardiol. 2022;354:22–28.
   PubMed Web of Science ®Google Scholar
• Maurizi N, Chiriatti C, Fumagalli C, et al. Real-world use and predictors of response to disopyramide in patients with obstructive hypertrophic cardiomyopathy. J Clin Med. 2023;12(7):2725. DOI:10.3390/jcm12072725
   PubMed Web of Science ®Google Scholar
• Toepfer CN, Garfinkel AC, Venturini G, et al. Myosin sequestration regulates sarcomere function, cardiomyocyte energetics, and metabolism, informing the pathogenesis of hypertrophic cardiomyopathy. Circulation. 2020;141(10):828–842. DOI:10.1161/CIRCULATIONAHA.119.042339
   PubMed Web of Science ®Google Scholar
• Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J. 2014;106(6):1236–1249.
   PubMed Web of Science ®Google Scholar
• Alamo L, Ware JS, Pinto A, et al. Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes. Elife. 2017;6:e24634.
   PubMed Web of Science ®Google Scholar
• Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018;138(14):1387–1398. DOI:10.1161/CIRCULATIONAHA.117.033200
   PubMed Web of Science ®Google Scholar
• García-Giustiniani D, Arad M, Ortíz-Genga M, et al. Phenotype and prognostic correlations of the converter region mutations affecting the β myosin heavy chain. Heart. 2015;101(13):1047–1053. DOI:10.1136/heartjnl-2014-307205
   PubMed Web of Science ®Google Scholar
• Forsey J, Benson L, Rozenblyum E, et al. Early changes in apical rotation in genotype positive children with hypertrophic cardiomyopathy mutations without hypertrophic changes on two-dimensional imaging. J Am Soc Echocardiogr. 2014;27(2):215–221. DOI:10.1016/j.echo.2013.10.012
   PubMed Web of Science ®Google Scholar
• Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;351(6273):617–621. DOI:10.1126/science.aad3456
   PubMed Web of Science ®Google Scholar
• Kawas RF, Anderson RL, Ingle SRB, et al. A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle. J Biol Chem. 2017;292(40):16571–16577. DOI:10.1074/jbc.M117.776815
   PubMed Web of Science ®Google Scholar
• Stern JA, Markova S, Ueda Y, et al. A small molecule inhibitor of sarcomere contractility acutely relieves left ventricular outflow tract obstruction in feline hypertrophic cardiomyopathy. PLoS ONE. 2016;11(12):e0168407. DOI:10.1371/journal.pone.0168407
   PubMed Web of Science ®Google Scholar
• Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten treatment for obstructive hypertrophic cardiomyopathy: a clinical trial. Ann Intern Med. 2019;170(11):741–748. DOI:10.7326/M18-3016
   PubMed Web of Science ®Google Scholar
• Extension study of mavacamten (MYK-461) In adults with symptomatic obstructive hypertrophic cardiomyopathy previously enrolled in PIONEER (PIONEER-OLE). ClinicalTrials.Gov identifier: nCT03496168. Updated Jun 14, 2022. https://clinicaltrials.gov/ct2/show/NCT03496168
   Google Scholar
• Ho CY, Mealiffe ME, Bach RG, et al. Evaluation of mavacamten in symptomatic patients with nonobstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2020;75(21):2649–2660. DOI:10.1016/j.jacc.2020.03.064
   PubMed Web of Science ®Google Scholar
• A long-term safety extension study of mavacamten in adults who have completed MAVERICK-HCM or EXPLORER-HCM. ClinicalTrials.Gov Identifier: nCT03723655. Updated Sep 21, 2022. https://clinicaltrials.gov/ct2/show/NCT03723655.
   Google Scholar
• Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759–769. DOI:10.1016/S0140-6736(20)31792-X
   PubMed Web of Science ®Google Scholar
• Saberi S, Cardim N, Yamani M, et al. Mavacamten favorably impacts cardiac structure in obstructive hypertrophic cardiomyopathy: eXPLORER-HCM cardiac magnetic resonance substudy analysis. Circulation. 2021;143(6):606–608. DOI:10.1161/CIRCULATIONAHA.120.052359
   PubMed Web of Science ®Google Scholar
• Maron BJ, Maron MS, Sherrid MV, et al. Future role of new negative inotropic agents in the era of established surgical myectomy for symptomatic obstructive hypertrophic cardiomyopathy. J Am Heart Assoc. 2022;11(9):e024566. DOI:10.1161/JAHA.121.024566
   PubMed Web of Science ®Google Scholar
• Wheeler MT, Jacoby D, Elliott PM, et al. Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy. Eur J Heart Fail. 2023;25(2):260–270. DOI:10.1002/ejhf.2737
   PubMed Web of Science ®Google Scholar
• Desai MY, Owens A, Geske JB, et al. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy. J Am Coll Cardiol. 2022;80(2):95–108. DOI:10.1016/j.jacc.2022.04.048
   PubMed Web of Science ®Google Scholar
• Center for Drug Evaluation and Research. “FDA approves new drug to improve heart function.” U.S. Food and Drug Administration, FDA, https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-improve-heart-function-adults-rare-heart-condition.
   Google Scholar
• Grillo MP, Erve JCL, Dick R, et al. In vitro and in vivo pharmacokinetic characterization of mavacamten, a first-in-class small molecule allosteric modulator of beta cardiac myosin. Xenobiotica. 2019;49(6):718–733. DOI:10.1080/00498254.2018.1495856
   PubMed Web of Science ®Google Scholar
• Chuang C, Collibee S, Ashcraft L, et al. Discovery of aficamten (CK-274), a next-generation cardiac myosin inhibitor for the treatment of hypertrophic cardiomyopathy. J Med Chem. 2021;64(19):14142–14152. DOI:10.1021/acs.jmedchem.1c01290
   PubMed Web of Science ®Google Scholar
• Sharpe AN, Oldach MS, Rivas VN, et al. Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy. Sci Rep. 2023;13(1):32. DOI:10.1038/s41598-022-26630-z
   PubMed Web of Science ®Google Scholar
• Malik FI, Robertson LA, Armas DR, et al. A phase 1 dose-escalation study of the cardiac myosin inhibitor aficamten in healthy participants. JACC Basic Transl Sci. 2022;7(8):763–775. DOI:10.1016/j.jacbts.2022.04.008
   PubMedGoogle Scholar
• Maron MS, Masri A, Choudhury L, et al. REDWOOD-HCM steering committee and investigators. phase 2 study of aficamten in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2023;81(1):34–45. DOI:10.1016/j.jacc.2022.10.020
   PubMed Web of Science ®Google Scholar
• CY 6022 is an open label study to collect long-term safety and tolerability data for aficamten (CK-3773274) (FOREST-HCM). ClinicalTrials.Gov Identifier: nCT04848506. Last Updated: Jan 9, 2023. https://clinicaltrials.gov/ct2/show/NCT04848506.
   Google Scholar
• U. S. National Library of Medicine. CY 6031 study will evaluate the effects of treatment with aficamten (CK-3773274) over a 24-week period on cardiopulmonary exercise capacity and health status in patients with symptomatic oHCM (SEQUOIA-HCM). ClinicalTrials.Gov Identifier: nCT05186818. Last Updated: Jan 9, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05186818.
   Google Scholar
• Makavos G, Κairis C, Tselegkidi ME, et al. Hypertrophic cardiomyopathy: an updated review on diagnosis, prognosis, and treatment. Heart Fail Rev. 2019;24(4):439–459. DOI:10.1007/s10741-019-09775-4
   PubMed Web of Science ®Google Scholar
• Margara F, Psaras Y, Wang ZJ, et al. Mechanism based therapies enable personalised treatment of hypertrophic cardiomyopathy. Sci Rep. 2022;12(1):22501. DOI:10.1038/s41598-022-26889-2
   PubMed Web of Science ®Google Scholar
• Cazes M, Chassaing C, Martinet M, et al. Comparison of anticholinergic effects of cibenzoline, disopyramide, and atropine. J Cardiovasc Pharmacol. 1990;15(2):308–316. DOI:10.1097/00005344-199002000-00019
   PubMed Web of Science ®Google Scholar
• Hamada M, Shigematsu Y, Ikeda S, et al. Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy. Circulation. 1997;96(5):1520–1524. DOI:10.1161/01.CIR.96.5.1520
   PubMed Web of Science ®Google Scholar
• Igarashi H. The efficacy of cibenzoline for reducing the left ventricular pressure gradient of hypertrophic obstructive cardiomyopathy: a case report. J Med Ultrason. 2003;30(2):111–114.
   PubMedGoogle Scholar
• Hamada M, Shigematsu Y, Ikeda S, et al. Impact of cibenzoline treatment on left ventricular remodelling and prognosis in hypertrophic obstructive cardiomyopathy. ESC Heart Fail. 2021;8(6):4832–4842. DOI:10.1002/ehf2.13672
   PubMed Web of Science ®Google Scholar
• Hamada M, Ikeda S, Ohshima K, et al. Impact of chronic use of cibenzoline on left ventricular pressure gradient and left ventricular remodeling in patients with hypertrophic obstructive cardiomyopathy. J Cardiol. 2016;67(3):279–286. DOI:10.1016/j.jjcc.2015.05.014
   PubMed Web of Science ®Google Scholar
• A phase I study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ct-g20 in subjects with obstructive hypertrophic cardiomyopathy. ClinicalTrials.Gov Identifier: nCT04418297. Last Updated: Aug 15, 2022. https://clinicaltrials.gov/ct2/show/NCT04418297
   Google Scholar
• Coppini R, Ferrantini C, Yao L, et al. Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy. Circulation. 2013;127(5):575–584. DOI:10.1161/CIRCULATIONAHA.112.134932
   PubMed Web of Science ®Google Scholar
• Gentry JL 3rd, Mentz RJ, Hurdle M, et al. Ranolazine for treatment of angina or dyspnea in hypertrophic cardiomyopathy patients (RHYME). J Am Coll Cardiol. 2016;68(16):1815–1817. DOI:10.1016/j.jacc.2016.07.758
   PubMed Web of Science ®Google Scholar
• Olivotto I, Camici PG, Merlini PA, et al. Efficacy of ranolazine in patients with symptomatic hypertrophic cardiomyopathy: the RESTYLE-HCM randomized, double-blind, placebo-controlled study. Circ Heart Fail. 2018;11(1):e004124. DOI:10.1161/CIRCHEARTFAILURE.117.004124
   PubMed Web of Science ®Google Scholar
• Olivotto I, Hellawell JL, Farzaneh-Far R, et al. Novel approach targeting the complex pathophysiology of hypertrophic cardiomyopathy: the impact of late sodium current inhibition on exercise capacity in subjects with symptomatic hypertrophic cardiomyopathy (LIBERTY-HCM) trial. Circ Heart Fail. 2016;9(3):e002764. DOI:10.1161/CIRCHEARTFAILURE.115.002764
   PubMed Web of Science ®Google Scholar
• Effect of eleclazine (GS-6615) on exercise capacity in subjects with symptomatic hypertrophic cardiomyopathy (LIBERTY-HCM). ClinicalTrials.Gov identifier: nCT02291237. Updated Sep 24, 2018. https://clinicaltrials.gov/ct2/show/NCT02291237.
   Google Scholar
• Ashrafian H, Redwood C, Blair E, et al. Hypertrophic cardiomyopathy: a paradigm for myocardial energy depletion. Trends Genet. 2003;19(5):263–268. DOI:10.1016/S0168-9525(03)00081-7
   PubMed Web of Science ®Google Scholar
• Tuohy CV, Kaul S, Song HK, et al. Hypertrophic cardiomyopathy: the future of treatment. Eur J Heart Fail. 2020;22(2):228–240. DOI:10.1002/ejhf.1715
   PubMed Web of Science ®Google Scholar
• Ashrafian H, Horowitz JD, Frenneaux MP. Perhexiline. Cardiovasc Drug Rev. 2007;25(1):76–97.
   PubMed Web of Science ®Google Scholar
• Horowitz JD, Chirkov YY. Perhexiline and hypertrophic cardiomyopathy: a new horizon for metabolic modulation. Circulation. 2010;122(16):1547–1549.
   PubMed Web of Science ®Google Scholar
• Unger SA, Kennedy JA, McFadden-Lewis K, et al. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005;46(6):849–855. DOI:10.1097/01.fjc.0000190488.77434.f1
   PubMed Web of Science ®Google Scholar
• Abozguia K, Elliott P, McKenna W, et al. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010;122(16):1562–1569. DOI:10.1161/CIRCULATIONAHA.109.934059
   PubMed Web of Science ®Google Scholar
• Ananthakrishna R, Lee SL, Foote J, et al. Randomized controlled trial of perhexiline on regression of left ventricular hypertrophy in patients with symptomatic hypertrophic cardiomyopathy (RESOLVE-HCM trial). Am Heart J. 2021;240:101–113.
   PubMed Web of Science ®Google Scholar
• Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol. 2003;17(2):133–145.
   PubMed Web of Science ®Google Scholar
• Coats CJ, Pavlou M, Watkinson OT, et al. Effect of trimetazidine dihydrochloride therapy on exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy: a randomized clinical trial. JAMA Cardiol. 2019;4(3):230–235. DOI:10.1001/jamacardio.2018.4847
   PubMed Web of Science ®Google Scholar
• Tremaine L, Al-Fayoumi S, Wetering J, et al. Abstract 10372: a clinical drug-drug interaction study of Imb-1018972, a novel investigational cardiac mitotrope in phase 2 development for the treatment of myocardial ischemia and hypertrophic cardiomyopathy. Circulation. 2021;144(Suppl_1):A10372. DOI:10.1161/circ.144.suppl_1.10372
   Google Scholar
• Vriesendorp PA, Schinkel AFL, de Groot NMS, et al. Impact of adverse left ventricular remodeling on sudden cardiac death in patients with hypertrophic cardiomyopathy. Clin Cardiol. 2014;37(8):493–498. DOI:10.1002/clc.22293
   PubMed Web of Science ®Google Scholar
• Musumeci B, Tini G, Russo D, et al. Left ventricular remodeling in hypertrophic cardiomyopathy: an overview of current knowledge. J Clin Med. 2021;10(8):1547. DOI:10.3390/jcm10081547
   PubMed Web of Science ®Google Scholar
• Habib M, Adler A, Fardfini K, et al. Progression of myocardial fibrosis in hypertrophic cardiomyopathy: a cardiac magnetic resonance study. JACC Cardiovasc Imaging. 2021;14(5):947–958. DOI:10.1016/j.jcmg.2020.09.037
   PubMed Web of Science ®Google Scholar
• Barreras A, Gurk-Turner C. Angiotensin II receptor blockers. Proc (Bayl Univ Med Cent). 2003;16(1):123–126.
   PubMedGoogle Scholar
• Olivotto I, Ashley EA. INHERIT (INHibition of the renin angiotensin system in hypertrophic cardiomyopathy and the effect on hypertrophy—a randomised intervention trial with losartan). Glob Cardiol Sci Pract. 2015;2015(1):7.
   PubMedGoogle Scholar
• Axelsson Raja A, Shi L, Day SM, et al. Baseline characteristics of the VANISH cohort. Circ Heart Fail. 2019;12(12):e006231. DOI:10.1161/CIRCHEARTFAILURE.119.006231
   PubMed Web of Science ®Google Scholar
• Sacubitril/Valsartan vs lifestyle in hypertrophic cardiomyopathy (SILICOFCM). ClinicalTrials.Gov identifier: nCT03832660. Updated Nov 28, 2022. https://beta.clinicaltrials.gov/study/NCT03832660.
   Google Scholar
• Wu CT, Wang ZH, Li ZQ, et al. Effect of spironolactone on cardiac remodeling after acute myocardial infarction. World J Emerg Med. 2013;4(1):48–53. DOI:10.5847/wjem.j.issn.1920-8642.2013.01.009
   PubMedGoogle Scholar
• Dimas V, Ayers C, Daniels J, et al. Spironolactone therapy is associated with reduced ventricular tachycardia rate in patients with cardiomyopathy. Pacing Clin Electrophysiol. 2011;34(3):309–314. DOI:10.1111/j.1540-8159.2010.02888.x
   PubMed Web of Science ®Google Scholar
• “Aldactone®clinical pharmacology (Spironolactone).” ALDACTONE® Clinical Pharmacology (Spironolactone) | Pfizer Medical Information. https://www.pfizermedicalinformation.com/en-us/aldactone/clinical-pharmacology#:~:text=12.3%20Pharmacokinetics&text=The%20mean%20time%20to%20reach,AUC.
   Google Scholar
• Evaluating the effect of spironolactone on hypertrophic cardiomyopathy. ClinicalTrials.Gov Identifier: nCT02948998. Last updated: May 9, 2018. https://clinicaltrials.gov/ct2/show/NCT02948998
   Google Scholar
• Subramanian M, Sravani V, Krishna SP, et al. Efficacy of SGLT2 inhibitors in patients with diabetes and nonobstructive hypertrophic cardiomyopathy. Am J Cardiol. 2023;188:80–86.
   PubMed Web of Science ®Google Scholar
• Wilcox CS. Antihypertensive and renal mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors. Hypertension. 2020;75(4):894–901.
   PubMed Web of Science ®Google Scholar
• Li C, Zhang J, Xue M, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019;18(1):15. DOI:10.1186/s12933-019-0816-2
   PubMedGoogle Scholar
• Requena-Ibáñez JA, Santos-Gallego CG, Rodriguez-Cordero A, et al. Mechanistic insights of empagliflozin in nondiabetic patients with HFrEF: from the EMPA-TROPISM study. JACC Heart Fail. 2021;9(8):578–589. DOI:10.1016/j.jchf.2021.04.014
   PubMed Web of Science ®Google Scholar
• Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010;19(2):275–283.
   PubMed Web of Science ®Google Scholar
• Chen Z, Zhou H, Huang X, et al. Pirfenidone attenuates cardiac hypertrophy against isoproterenol by inhibiting activation of the janus tyrosine kinase-2/signal transducer and activator of transcription 3 (JAK-2/STAT3) signaling pathway. Bioengineered. 2022;13(5):12772–12782. DOI:10.1080/21655979.2022.2073145
   PubMed Web of Science ®Google Scholar
• Nguyen DT, Ding C, Wilson E, et al. Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias. Heart Rhythm. 2010;7(10):1438–1445. DOI:10.1016/j.hrthm.2010.04.030
   PubMed Web of Science ®Google Scholar
• Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54(3):201–211.
   PubMed Web of Science ®Google Scholar
• Helms AS, Thompson AD, Day SM. Translation of new and emerging therapies for genetic cardiomyopathies. JACC. 2022;7(1):70–83.
   Google Scholar
• Mearini G, Stimpel D, Geertz B, et al. Mybpc3 gene therapy for neonatal cardiomyopathy enables longterm disease prevention in mice. Nat Commun. 2014;5(1):5515. DOI:10.1038/ncomms6515
   PubMedGoogle Scholar
• Monteiro da Rocha A, Guerrero-Serna G, Helms A, et al. Deficient cMyBP-C protein expression during cardiomyocyte differentiation underlies human hypertrophic cardiomyopathy cellular phenotypes in disease specific human ES cell derived cardiomyocytes. J Mol Cell Cardiol. 2016;99(1):197–206. DOI:10.1016/j.yjmcc.2016.09.004
   PubMedGoogle Scholar
• Iavarone M, Monda E, Vritz O, et al. Medical treatment of patients with hypertrophic cardiomyopathy: an overview of current and emerging therapy. Arch Cardiovasc Dis. 2022;115(10):529–537. DOI:10.1016/j.acvd.2022.06.003
   PubMed Web of Science ®Google Scholar
• Mentias A, Smedira NG, Krishnaswamy A, et al. Survival after septal reduction in patients >65 years old with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2023;81(2):105–115. DOI:10.1016/j.jacc.2022.10.027
   PubMed Web of Science ®Google Scholar