388
Views
4
CrossRef citations to date
0
Altmetric
REVIEW

Familial Hypertrophic Cardiomyopathy: Diagnosis and Management

, & ORCID Icon
Pages 211-221 | Received 22 Nov 2022, Accepted 28 Mar 2023, Published online: 06 Apr 2023

References

  • Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary artery risk development in (young) adults. Circulation. 1995;92:785–789. doi:10.1161/01.cir.92.4.785
  • Maron BJ. Clinical Course and management of hypertrophic cardiomyopathy. N Engl J Med. 2018;379:1977. doi:10.1056/NEJMc1812159
  • Zou Y, Song L, Wang Z, et al. Prevalence of idiopathic hypertrophic cardiomyopathy in China: a population-based echocardiographic analysis of 8080 adults. Am J Med. 2004;116:14–18. doi:10.1016/j.amjmed.2003.05.009
  • Maron BJ, Desai MY, Nishimura RA, et al. Management of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2022;79:390–414. doi:10.1016/j.jacc.2021.11.021
  • 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;138:1387–1398. doi:10.1161/CIRCULATIONAHA.117.033200
  • Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2020;142:e533–e557. doi:10.1161/CIR.0000000000000938
  • Hada Y, Sakamoto T, Amano K, et al. Prevalence of hypertrophic cardiomyopathy in a population of adult Japanese workers as detected by echocardiographic screening. Am J Cardiol. 1987;59:183–184. doi:10.1016/s0002-9149(87)80107-8
  • Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res. 2017;121:749–770. doi:10.1161/CIRCRESAHA.117.311059
  • Maron BJ, Mathenge R, Casey SA, Poliac LC, Longe TF. Clinical profile of hypertrophic cardiomyopathy identified de novo in rural communities. J Am Coll Cardiol. 1999;33:1590–1595. doi:10.1016/s0735-1097(99)00039-x
  • Siontis KC, Ommen SR, Geske JB. Sex, survival, and cardiomyopathy: differences between men and women with hypertrophic cardiomyopathy. J Am Heart Assoc. 2019;8:e014448. doi:10.1161/JAHA.119.014448
  • Geske JB, Ong KC, Siontis KC, et al. Women with hypertrophic cardiomyopathy have worse survival. Eur Heart J. 2017;38:3434–3440. doi:10.1093/eurheartj/ehx527
  • Butters A, Lakdawala NK, Ingles J. Sex differences in hypertrophic cardiomyopathy: interaction with genetics and environment. Curr Heart Fail Rep. 2021;18:264–273. doi:10.1007/s11897-021-00526-x
  • Patlolla SH, Schaff HV, Nishimura RA, et al. Sex and race disparities in hypertrophic cardiomyopathy: unequal implantable cardioverter-defibrillator use during hospitalization. Mayo Clin Proc. 2022;97:507–518. doi:10.1016/j.mayocp.2021.07.022
  • Pedram A, Razandi M, Lubahn D, et al. Estrogen inhibits cardiac hypertrophy: role of estrogen receptor-beta to inhibit calcineurin. Endocrinology. 2008;149:3361–3369. doi:10.1210/en.2008-0133
  • Haines CD, Harvey PA, Luczak ED, et al. Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease. Endocrinology. 2012;153:4470–4479. doi:10.1210/en.2012-1391
  • Trongtorsak A, Polpichai N, Thangjui S, et al. Gender-related differences in hypertrophic cardiomyopathy: a systematic review and meta-analysis. Pulse. 2021;9:38–46. doi:10.1159/000517618
  • Dubey RK, Imthurn B, Zacharia LC, Jackson EK. Hormone replacement therapy and cardiovascular disease: what went wrong and where do we go from here? Hypertension. 2004;44:789–795. doi:10.1161/01.HYP.0000145988.95551.28
  • Sankaranarayanan R, Fleming EJ, Garratt CJ. Mimics of hypertrophic cardiomyopathy - diagnostic clues to aid early identification of phenocopies. Arrhythm Electrophysiol Rev. 2013;2:36–40. doi:10.15420/aer.2013.2.1.36
  • Hoss S, Habib M, Silver J, et al. Genetic testing for diagnosis of hypertrophic cardiomyopathy mimics: yield and clinical significance. Circ Genom Precis Med. 2020;13:e002748. doi:10.1161/CIRCGEN.119.002748
  • Wilcox NS, Prenner SB, Cevasco M, et al. End stage mitochondrial cardiomyopathy and heart transplantation due to biallelic pathogenic C1QBP variants. Circulation. 2022;15:e003559. doi:10.1161/CIRCGEN.121.003559
  • Maron BJ, Gottdiener JS, Epstein SE. Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. A wide angle, two dimensional echocardiographic study of 125 patients. Am J Cardiol. 1981;48:418–428. doi:10.1016/0002-9149(81)90068-0
  • Syed IS, Ommen SR, Breen JF, Tajik AJ. Hypertrophic cardiomyopathy: identification of morphological subtypes by echocardiography and cardiac magnetic resonance imaging. JACC Cardiovasc Imaging. 2008;1:377–379. doi:10.1016/j.jcmg.2008.02.008
  • Turer AT, Samad Z, Valente AM, et al. Anatomic and clinical correlates of septal morphology in hypertrophic cardiomyopathy. Eur J Echocardiogr. 2011;12:131–139. doi:10.1093/ejechocard/jeq163
  • Azechi N, Morita Y, Inoue M, Kuzuyama R, Imataka K. Age-associated morphological change in interventricular septum. Rinsho Byori. 1993;41:285–288. Japanese.
  • Krasnow N. Subaortic septal bulge simulates hypertrophic cardiomyopathy by angulation of the septum with age, independent of focal hypertrophy. An echocardiographic study. J Am Soc Echocardiogr. 1997;10:545–555. doi:10.1016/s0894-7317(97)70009-9
  • Toth AB, Engel JA, McManus AM, McManus BM. Sigmoidity of the ventricular septum revisited: progression in early adulthood, predominance in men, and Independence from cardiac mass. Am J Cardiovasc Pathol. 1988;2:211–223.
  • Canepa M, Pozios I, Vianello PF, et al. Distinguishing ventricular septal bulge versus hypertrophic cardiomyopathy in the elderly. Heart. 2016;102:1087–1094. doi:10.1136/heartjnl-2015-308764
  • Diaz T, Pencina MJ, Benjamin EJ, et al. Prevalence, clinical correlates, and prognosis of discrete upper septal thickening on echocardiography: the Framingham Heart Study. Echocardiography. 2009;26:247–253. doi:10.1111/j.1540-8175.2008.00806.x
  • Mendez C, Soler R, Rodríguez E, et al. Differential diagnosis of thickened myocardium: an illustrative MRI review. Insights Imaging. 2018;9:695–707. doi:10.1007/s13244-018-0655-9
  • Valente AM, Lakdawala NK, Powell AJ, et al. Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy. Circ Cardiovasc Genet. 2013;6:230–237. doi:10.1161/CIRCGENETICS.113.000037
  • Niimura H, Bachinski LL, Sangwatanaroj S, et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998;338:1248–1257. doi:10.1056/NEJM199804303381802
  • Millat G, Bouvagnet P, Chevalier P, et al. Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. Eur J Med Genet. 2010;53:261–267. doi:10.1016/j.ejmg.2010.07.007
  • Kaski JP, Syrris P, Esteban MTT, et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2009;2:436–441. doi:10.1161/CIRCGENETICS.108.821314
  • Bick AG, Flannick J, Ito K, et al. Burden of rare sarcomere gene variants in the Framingham and Jackson heart study cohorts. Am J Hum Genet. 2012;91:513–519. doi:10.1016/j.ajhg.2012.07.017
  • Teekakirikul P, Zhu W, Huang HC, Fung E. Hypertrophic cardiomyopathy: an overview of genetics and management. Biomolecules. 2019;9:878. doi:10.3390/biom9120878
  • Littler WA. Twin studies in hypertrophic cardiomyopathy. Br Heart J. 1972;34:1147–1151. doi:10.1136/hrt.34.11.1147
  • Repetti GG, Kim Y, Pereira AC, et al. Discordant clinical features of identical hypertrophic cardiomyopathy twins. Proc Natl Acad Sci USA. 2021;118. doi:10.1073/pnas.2021717118
  • Olivotto I, Maron BJ, Tomberli B, et al. Obesity and its association to phenotype and clinical course in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;62:449–457. doi:10.1016/j.jacc.2013.03.062
  • Fumagalli C, Maurizi N, Day SM, et al. Association of obesity with adverse long-term outcomes in hypertrophic cardiomyopathy. JAMA Cardiol. 2020;5:65–72. doi:10.1001/jamacardio.2019.4268
  • Nollet EE, Westenbrink BD, de Boer RA, Kuster DWD, van der Velden J. Unraveling the genotype-phenotype relationship in hypertrophic cardiomyopathy: obesity-related cardiac defects as a major disease modifier. J Am Heart Assoc. 2020;9:e018641. doi:10.1161/JAHA.120.018641
  • Chen Z, Xu B. Clinical significance of overweight in patients with hypertrophic cardiomyopathy: a retrospective cohort study. Medicine. 2021;100:e27445. doi:10.1097/MD.0000000000027445
  • Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol. 2015;22:13–19. doi:10.1177/2047487313501277
  • Limongelli G, Monda E, D’Aponte A, et al. Combined effect of Mediterranean diet and aerobic exercise on weight loss and clinical status in obese symptomatic patients with hypertrophic cardiomyopathy. Heart Fail Clin. 2021;17:303–313. doi:10.1016/j.hfc.2021.01.003
  • Petto J, DE Oliveira EC, DE Almeida RVA, et al. Reverse myocardial remodeling in hypertrophic cardiomyopathy: little explored benefit of exercise. Int J Exerc Sci. 2021;14:1018–1026.
  • Saberi S, Wheeler M, Day SM. Exercise for patients with hypertrophic cardiomyopathy-reply. JAMA. 2017;318:481–482. doi:10.1001/jama.2017.8201
  • Kwon DH, Smedira NG, Popovic ZB, et al. Steep left ventricle to aortic root angle and hypertrophic obstructive cardiomyopathy: study of a novel association using three-dimensional multimodality imaging. Heart. 2009;95:1784–1791. doi:10.1136/hrt.2009.166777
  • Critoph CH, Pantazis A, Tome Esteban MT, et al. The influence of aortoseptal angulation on provocable left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Open Heart. 2014;1:e000176. doi:10.1136/openhrt-2014-000176
  • Maron MS, Olivotto I, Harrigan C, et al. Mitral valve abnormalities identified by cardiovascular magnetic resonance represent a primary phenotypic expression of hypertrophic cardiomyopathy. Circulation. 2011;124:40–47. doi:10.1161/CIRCULATIONAHA.110.985812
  • Makavos G, Κairis C, Tselegkidi M-E, et al. Hypertrophic cardiomyopathy: an updated review on diagnosis, prognosis, and treatment. Heart Fail Rev. 2019;24:439–459. doi:10.1007/s10741-019-09775-4
  • Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;45:1251–1258. doi:10.1016/j.jacc.2005.01.012
  • Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;351:617–621. doi:10.1126/science.aad3456
  • 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;66:1307–1308. doi:10.1016/j.jacc.2015.06.1333
  • Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and the society for cardiovascular angiography and interventions. J Am Coll Cardiol. 2011;58:e44–122. doi:10.1016/j.jacc.2011.08.007
  • Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;46:470–476. doi:10.1016/j.jacc.2005.02.090
  • Day SM, Tardiff JC, Ostap EM. Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure. J Clin Invest. 2022;132. doi:10.1172/JCI148557
  • Nag S, Trivedi DV, Sarkar SS, et al. The myosin Mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations. Nat Struct Mol Biol. 2017;24:525–533. doi:10.1038/nsmb.3408
  • Scellini B, Piroddi N, Dente M, et al. Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle. J Gen Physiol. 2021;153. doi:10.1085/jgp.202012789
  • Anderson RL, Trivedi DV, Sarkar SS, et al. Deciphering the super relaxed state of human beta-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers. Proc Natl Acad Sci USA. 2018;115:E8143–E8152. doi:10.1073/pnas.1809540115
  • Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten treatment for obstructive hypertrophic cardiomyopathy: a clinical trial. Ann Intern Med. 2019;170:741–748. doi:10.7326/M18-3016
  • 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;396:759–769. doi:10.1016/S0140-6736(20)31792-X
  • 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;143:606–608. doi:10.1161/CIRCULATIONAHA.120.052359
  • 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;80:95–108. doi:10.1016/j.jacc.2022.04.048
  • 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;64:14142–14152. doi:10.1021/acs.jmedchem.1c01290
  • 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;7:763–775. doi:10.1016/j.jacbts.2022.04.008
  • Maron MS, Masri A, Choudhury L, et al. Phase 2 study of aficamten in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2023;81:34–45. doi:10.1016/j.jacc.2022.10.020
  • ClinicalTrials.gov. 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). Available from: https://clinicaltrials.gov/ct2/show/NCT05186818. Accessed March 28, 2023.
  • Del Rio CL, Yadav A, Ferguson BS, et al. Chronic treatment with a mavacamten-like myosin-modulator (MYK-581) blunts disease progression in a mini-pig genetic model of non-obstructed hypertrophic cardiomyopathy: in vivo evidence for improved relaxation and functional reserve. Circulation. 2019;140:A14585–A14585.
  • Ferguson B, Stern JA, Oldach MS, et al. Acute effects of a mavacamten-like myosin-inhibitor (MYK-581) in a feline model of obstructed hypertrophic cardiomyopathy: evidence of improved ventricular filling (beyond obstruction reprieve). Eur Heart J. 2020;41:ehaa946. doi:10.1093/ehjci/ehaa946.3713
  • Ho CY, Mealiffe ME, Bach RG, et al. Evaluation of mavacamten in symptomatic patients with nonobstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2020;75:2649–2660. doi:10.1016/j.jacc.2020.03.064
  • Ho CY, Day SM, Axelsson A, et al. Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial. Nat Med. 2021;27:1818–1824. doi:10.1038/s41591-021-01505-4
  • Maron BJ, Rowin EJ, Maron MS. Evolution of risk stratification and sudden death prevention in hypertrophic cardiomyopathy: twenty years with the implantable cardioverter-defibrillator. Heart Rhythm. 2021;18:1012–1023. doi:10.1016/j.hrthm.2021.01.019
  • 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;115:529–537. doi:10.1016/j.acvd.2022.06.003
  • Packard E, de Feria A, Peshin S, Reza N, Owens AT. Contemporary therapies and future directions in the management of hypertrophic cardiomyopathy. Cardiol Ther. 2022;11:491–507. doi:10.1007/s40119-022-00283-5
  • Repetti GG, Toepfer CN, Seidman JG, Seidman CE. Novel therapies for prevention and early treatment of cardiomyopathies. Circ Res. 2019;124:1536–1550. doi:10.1161/CIRCRESAHA.119.313569
  • Prondzynski M, Krämer E, Laufer SD, et al. Evaluation of MYBPC3 trans-splicing and gene replacement as therapeutic options in human iPSC-derived cardiomyocytes. Mol Ther Nucleic Acids. 2017;7:475–486. doi:10.1016/j.omtn.2017.05.008
  • da Rocha AM, 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;99:197–206. doi:10.1016/j.yjmcc.2016.09.004
  • Chai AC, Cui M, Chemello F, et al. Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat Med. 2023;11:1.
  • Iyer AA, Saade D, Bharucha-Goebel D, et al. Ethical challenges for a new generation of early-phase pediatric gene therapy trials. Genet Med. 2021;23:2057–2066. doi:10.1038/s41436-021-01245-3
  • Maron MS, Kalsmith BM, Udelson JE, Li W, DeNofrio D. Survival after cardiac transplantation in patients with hypertrophic cardiomyopathy. Circ Heart Fail. 2010;3:574–579. doi:10.1161/CIRCHEARTFAILURE.109.922872
  • Fowler CC, Helmers MR, Smood B, et al. The modified US heart allocation system improves transplant rates and decreases status upgrade utilization for patients with hypertrophic cardiomyopathy. J Heart Lung Transplant. 2021;40:1181–1190. doi:10.1016/j.healun.2021.06.018