Abstract
Cardiomyopathies are diseases of the myocardium associated with cardiac dysfunction. According to the World Health Organization (WHO) classification, cardiomyopathies are classified either as primary or secondary cardiomyopathies. Based on morphological and functional criteria, heritable cardiomyopathies are classified into four primary categories including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). More recently, left ventricular non-compaction (LVNC) syndrome has been recognized as a separate cardiomyopathy. Secondary cardiomyopathies include for example ischemic and hypertensive cardiomyopathy. This chapter focuses solely on HCM, the most common heritable cardiovascular disease (estimated prevalence 1:500) and the most common cause of sudden cardiac death (SCD) in young adolescents and athletes. This chapter discusses HCM’s clinical and genetic substrate, genetic testing and screening, and has particular focus on its arrhythmogenic features and the role and indication of the implantable cardioverter defibrillator (ICD) and prevention of SCD.
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References
Yetman AT, McCrindle BW. Management of pediatric hypertrophic cardiomyopathy. Curr Opin Cardiol. 2005;20:80–3.
Poliac LC, Barron ME, Maron BJ. Hypertrophic cardiomyopathy. Anesthesiology. 2006;104:183–92.
Maron BJ, Seidman JG, Seidman CE. Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:2125–32.
Franz WM, Muller OJ, Katus HA. Cardiomyopathies: from genetics to the prospect of treatment. Lancet. 2001;358:1627–37.
Ellsworth EG, Ackerman MJ. The changing face of sudden cardiac death in the young. Heart Rhythm. 2005;2:1283–5.
Puranik R, Chow CK, Duflou JA, Kilborn MJ, McGuire MA. Sudden death in the young. Heart Rhythm. 2005;2:1277–82.
Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the united states, 1980–2006. Circulation. 2009;119:1085–92.
Corrado D, Basso C, Thiene G. Sudden cardiac death in young people with apparently normal heart. Cardiovasc Res. 2001;50:399–408.
Roberts R, Sigwart U. Current concepts of the pathogenesis and treatment of hypertrophic cardiomyopathy. Circulation. 2005;112:293–6.
Klein GJ, Krahn AD, Skanes AC, Yee R, Gula LJ. Primary prophylaxis of sudden death in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy. J Cardiovasc Electrophysiol. 2005;16(Suppl 1):S28–34.
Elliott PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severtiy of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet. 2001;357:420–4.
Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for practice guidelines. J Am Coll Cardiol. 2003;42:1687–713.
Debl K, Djavidani B, Buchner S, Lipke C, Nitz W, Feuerbach S, et al. Delayed hyperenhancement: frequent finding in magnetic resonance imaging of left ventricular hypertrophy due to aortic stenosis and hypertrophic cardiomyopathy. Heart. 2006;92(10):1447–51.
Moon JC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ. Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am Coll Cardiol. 2003;41:1561–7.
Binder J, Ommen SR, Gersh BJ, Van Driest SL, Tajik AJ, Nishimura RA, et al. Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations. Mayo Clin Proc. 2006;81:459–67.
Lever HM, Karam RF, Currie PJ, Healy BP. Hypertrophic cardiomyopathy in the elderly. Distinctions from the young based on cardiac shape. Circulation. 1989;79:580–9.
Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287:1308–20.
Maron BJ, Carney KP, Lever HM, Lewis JF, Barac I, Casey SA, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41:974–80.
Spirito P, Maron BJ, Bonow RO, Epstein SE. Occurrence and significance of progressive left ventricular wall thinning and relative cavity dilatation in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60:123–9.
Boriani G, Maron BJ, Shen WK, Spirito P. Prevention of sudden death in hypertrophic cardiomyopathy: but which defibrillator for which patient? Circulation. 2004;110:e438–42.
Wolf CM, Moskowitz IP, Arno S, Branco DM, Semsarian C, Bernstein SA, et al. Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia. Proc Natl Acad Sci USA. 2005;102:18123–8.
Tomaselli GF, Marban E. Electrophysiological remodeling in hypertrophy and heart failure. Cardiovasc Res. 1999;42:270–83.
Antzelevitch C. Molecular genetics of arrhythmias and cardiovascular conditions associated with arrhythmias. J Cardiovasc Electrophysiol. 2003;14:1259–72.
Olivotto I, Cecchi F, Casey SA, Dolara A, Traverse JH, Maron BJ. Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy. Circulation. 2001;104:2517–24.
Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ. 2006;332:1251–5.
Attari M, Dhala A. Role of invasive and noninvasive testing in risk stratification of sudden cardiac death in children and young adults: an electrophysiologic perspective. Pediatr Clin North Am. 2004;51:1355–78.
Arad M, Maron BJ, Gorham JM, Johnson WH Jr, Saul JP, Perez-Atayde AR, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. 2005;352(4):362–72.
Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ. Spectrum and prognostic significance of arrhythmias on ambulatory holter electrocardiogram in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;45:697–704.
Van Driest SL, Vasile VC, Ommen SR, Will ML, Gersh BJ, Nishimura RA, et al. Myosin binding protein c mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:1903–10.
Van Driest SL, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Yield of genetic testing in hypertrophic cardiomyopathy. Mayo Clin Proc. 2005;80:739–44.
Van Driest SL, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Sarcomeric genotyping in hypertrophic cardiomyopathy. Mayo Clin Proc. 2005;80:463–9.
Ackerman MJ. Genetic testing for risk stratification in hypertrophic cardiomyopathy and long QT syndrome: fact or fiction? Curr Opin Cardiol. 2005;20:175–81.
Seidman JG, Seidman C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell. 2001;104:557–67.
Maron BJ, Tajik AJ, Ruttenberg HD, Graham TP, Atwood GF, Victorica BE, et al. Hypertrophic cardiomyopathy in infants: clinical features and natural history. Circulation. 1982;65:7–17.
Olivotto I, Girolami F, Ackerman MJ, Nistri S, Bos JM, Zachara E, et al. Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clin Proc. 2008;83:630–8.
Arad M, Maron BJ, Gorham JM, Johnson Jr WH, Saul JP, Perez-Atayde AR, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. 2005;352:362–72.
Daw EW, Chen SN, Czernuszewicz G, Lombardi R, Lu Y, Ma J, et al. Genome-wide mapping of modifier chromosomal loci for human hypertrophic cardiomyopathy. Hum Mol Genet. 2007;16:2463–71.
Lind JM, Chiu C, Ingles J, Yeates L, Humphries SE, Heather AK, et al. Sex hormone receptor gene variation associated with phenotype in male hypertrophic cardiomyopathy patients. J Mol Cell Cardiol. 2008;45:217–22.
Perkins MJ, Van Driest SL, Ellsworth EG, Will ML, Gersh BJ, Ommen SR, et al. Gene-specific modifying effects of pro-LVH polymorphisms involving the renin-angiotensin-aldosterone system among 389 unrelated patients with hypertrophic cardiomyopathy. Eur Heart J. 2005;26:2457–62.
Force T, Bonow RO, Houser SR, Solaro RJ, Hershberger RE, Adhikari B, et al. Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung, and Blood Institute. Circulation. 2010;122:1130–3.
Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression. Nature clinical practice. Cardiovasc Med. 2008;5:158–68.
Olivotto I, Cecchi F, Poggesi C, Yacoub MH. Developmental origins of hypertrophic cardiomyopathy phenotypes: a unifying hypothesis. Nature reviews. Cardiology. 2009;6:317–21.
Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, et al. Alpha-tropomyosin and cardiac troponin t mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994;77:701–12.
Tyska MJ, Hayes E, Giewat M, Seidman CE, Seidman JG, Warshaw DM. Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy. Circ Res. 2000;86:737–44.
Debold EP, Schmitt JP, Patlak JB, Beck SE, Moore JR, Seidman JG, et al. Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse alpha-cardiac myosin in the laser trap assay. Am J Physiol Heart Circ Physiol. 2007;293:H284–91.
Fatkin D, McConnell BK, Mudd JO, Semsarian C, Moskowitz IG, Schoen FJ, et al. An abnormal Ca(2+) response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy. J Clin Invest. 2000;106:1351–9.
Frey N, Luedde M, Katus HA. Mechanisms of disease: hypertrophic cardiomyopathy. Nat Rev Cardiol. 2011;9:91–100.
Van Driest SV, Ackerman MJ, Ommen SR, Shakur R, Will ML, Nishimura RA, et al. Prevalence and severity of “benign” mutations in the beta myosin heavy chain, cardiac troponin-T, and alpha tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002;106:3085–90.
Ackerman MJ, Van Driest SV, Ommen SR, Will ML, Nishimura RA, Tajik AJ, et al. Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T gene in hypertrophic cardiomyopathy: a comprehensive outpatient perspective. J Am Coll Cardiol. 2002;39:2042–8.
Olivotto I, Maron BJ, Montereggi A, Mazzuoli F, Dolara A, Cecchi F. Prognostic value of systemic blood pressure response during exercise in a community-based patient population with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1999;33:2044–51.
Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342:1778–85.
Maron BJ. Hypertrophic cardiomyopathy in childhood. Pediatr Clin North Am. 2004;51:1305–46.
Sorajja P, Nishimura RA, Ommen SR, Ackerman MJ, Tajik AJ, Gersh BJ. Use of echocardiography in patients with hypertrophic cardiomyopathy: clinical implications of massive hypertrophy. J Am Soc Echocardiogr. 2006;19:788–95.
Maron BJ. The electrocardiogram as a diagnostic tool for hypertrophic cardiomyopathy: revisited. Ann Noninvasive Electrocardiol. 2001;6:277–9.
Christiaans I, van Engelen K, van Langen IM, Birnie E, Bonsel GJ, Elliott PM, et al. Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy: systematic review of clinical risk markers. Europace. 2010;12:313–21.
Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic cardiomyopathy. N Engl J Med. 1997;336:775–85.
Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for practice guidelines. J Am Coll Cardiol. 2003;42:1687.
Adabag AS, Maron BJ, Appelbaum E, Harrigan CJ, Buros JL, Gibson CM, et al. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. J Am Coll Cardiol. 2008;51:1369–74.
Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, et al. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56:875–87.
Iles L, Pfluger H, Lefkovits L, Butler MJ, Kistler PM, Kaye DM, et al. Myocardial fibrosis predicts appropriate device therapy in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death. J Am Coll Cardiol. 2011;57:821–8.
Leonardi S, Raineri C, De Ferrari GM, Ghio S, Scelsi L, Pasotti M, et al. Usefulness of cardiac magnetic resonance in assessing the risk of ventricular arrhythmias and sudden death in patients with hypertrophic cardiomyopathy. Eur Heart J. 2009;30:2003–10.
Konno T, Shimizu M, Ino H, Fujino N, Hayashi K, Uchiyama K, et al. Phenotypic differences between electrocardiographic and echocardiographic determination of hypertrophic cardiomyopathy in genetically affected subjects. J Intern Med. 2005;258:216–24.
Konno T, Shimizu M, Ino H, Fujino N, Hayashi K, Uchiyama K, et al. Differences in diagnostic value of four electrocardiographic voltage criteria for hypertrophic cardiomyopathy in a genotyped population. Am J Cardiol. 2005;96:1308–12.
Maron BJ, Spirito P, Wesley Y, Arce J. Development and progression of left ventricular hypertrophy in children with hypertrophic cardiomyopathy. N Engl J Med. 1986;315:610–4.
Ozdemir O, Soylu M, Demir AD, Topaloglu S, Alyan O, Turhan H, et al. P-wave durations as a predictor for atrial fibrillation development in patients with hypertrophic cardiomyopathy. Int J Cardiol. 2004;94:163–6.
Franz WM, Müller OJ, Katus HA. Cardiomyopathies: from genetics to the prospect of treatment. Lancet. 2001;358:1627–37.
Frey N, Franz WM, Gloeckner K, Degenhardt M, Muller M, Muller O, et al. Transgenic rat hearts expressing a human cardiac troponin T deletion reveal diastolic dysfunction and ventricular arrhythmias. Cardiovasc Res. 2000;47:254–64.
Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O’Donoghue A, et al. Mutations in the genes for cardiac troponin t and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995;332:1058–65.
Watkins H, McKenna WJ. The prognostic impact of septal myectomy in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;46:477–9.
Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003;348:295–303.
Montgomery JV, Harris KM, Casey SA, Zenovich AG, Maron BJ. Relation of electrocardiographic patterns to phenotypic expression and clinical outcome in hypertrophic cardiomyopathy. Am J Cardiol. 2005;96:270–5.
Jouven X, Hagege A, Charron P, Carrier L, Dubourg O, Langlard JM, et al. Relation between qt duration and maximal wall thickness in familial hypertrophic cardiomyopathy. Heart. 2002;88:153–7.
Martin AB, Garson Jr A, Perry JC. Prolonged QT interval in hypertrophic and dilated cardiomyopathy in children. Am Heart J. 1994;127:64–70.
Uchiyama K, Hayashi K, Fujino N, Konno T, Sakamoto Y, Sakata K, et al. Impact of QT variables on clinical outcome of genotyped hypertrophic cardiomyopathy. Ann Noninvasive Electrocardiol. 2009;14:65–71.
Johnson JN, Grifoni C, Bos JM, Saber-Ayad M, Ommen SR, Nistri S, et al. Prevalence and clinical correlates of QT prolongation in patients with hypertrophic cardiomyopathy. Eur Heart J. 2011;32:1114–20.
Ostman-Smith I, Wettrell G, Keeton B, Riesenfeld T, Holmgren D, Ergander U. Echocardiographic and electrocardiographic identification of those children with hypertrophic cardiomyopathy who should be considered at high-risk of dying suddenly. Cardiol Young. 2005;15:632–42.
D’Andrea A, Caso P, Severino S, Scotto di Uccio F, Vigorito F, Ascione L, et al. Association between intraventricular myocardial systolic dyssynchrony and ventricular arrhythmias in patients with hypertrophic cardiomyopathy. Echocardiography. 2005;22:571–8.
Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet. 2004;363:1881–91.
Maron BJ. Contemporary considerations for risk stratification, sudden death and prevention in hypertrophic cardiomyopathy. Heart. 2003;89:977–8.
Nishimura RA, Holmes Jr DR. Clinical practice. Hypertrophic obstructive cardiomyopathy. N Engl J Med. 2004;350:1320–7.
Maron BJ, Dearani JA, Ommen SR, Maron MS, Schaff HV, Gersh BJ, et al. The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;44:2044–53.
Ommen SR, Maron BJ, Olivotto I, Maron MS, Cecchi F, Betocchi S, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;46:470–6.
Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006;113:1807–16.
Maron BJ, Nishimura RA, McKenna WJ, Rakowski H, Josephson ME, Kieval RS. Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-Pathy). Circulation. 1999;99:2927–33.
Chen MS, McCarthy PM, Lever HM, Smedira NG, Lytle BL. Effectiveness of atrial fibrillation surgery in patients with hypertrophic cardiomyopathy. Am J Cardiol. 2004;93:373–5.
Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA. 2007;298:405–12.
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011;124:2761–96.
DiMarco JP. Implantable cardioverter-defibrillators. N Engl J Med. 2003;349:1836–47.
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011;124:e783–831.
Maron BJ, Estes NAM, Maron MS, Almquist AK, Link MS, Udelson JE. Primary prevention of sudden death as a novel treatment strategy in hypertrophic cardiomyopathy. Circulation. 2003;107:2872–5.
Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8:1308–39.
Maron BJ, Pelliccia A, Spirito P. Cardiac disease in young trained athletes. Insights into methods for distinguishing athlete’s heart from structural heart disease, with particular emphasis on hypertrophic cardiomyopathy. Circulation. 1995;91:1596–601.
Maron BJ, Chaitman BR, Ackerman MJ, BayesdeLuna A, Corrado D, Crosson JE, et al. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation. 2004;109:2807–16.
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Bos, J.M., Ommen, S.R., Ackerman, M.J. (2013). Arrhythmias and Arrhythmia Management in Hypertrophic Cardiomyopathy. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4978-1_2
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