Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a wide spectrum of clinical manifestations. Patients can be asymptomatic or suffer major adverse events including sudden cardiac death, ventricular arrhythmias, and heart failure. Identification of individuals with HCM who are at risk for these complications remains challenging. While echocardiography remains the mainstay of diagnostic evaluation, cardiac magnetic resonance imaging (CMR) is an important adjunctive diagnostic modality with emerging applications for risk-stratification of adverse events in the HCM population. Although not included in current guidelines for HCM management, there is increasing evidence to support the use of CMR for routine prognostic assessment of HCM patients. In this review we discuss the use of CMR techniques, including late gadolinium enhancement, T1 mapping, and quantification of extracellular volume fraction, for the risk stratification of three major adverse events in HCM: sudden cardiac death, ventricular arrhythmias, and congestive heart failure.
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References
Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE (1995) 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 92(4):785–789
Rowin EJ, Maron MS, Chan RH, Hausvater A, Wang W, Rastegar H, Maron BJ (2017) Interaction of Adverse Disease Related Pathways in Hypertrophic Cardiomyopathy. Am J Cardiol 120(12):2256–2264. https://doi.org/10.1016/j.amjcard.2017.08.048
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW (2011) 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 124(24):e783–e831. https://doi.org/10.1161/CIR.0b013e318223e2bd
Christiaans I, van Engelen K, van Langen IM, Birnie E, Bonsel GJ, Elliott PM, Wilde AAM (2010) Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy: systematic review of clinical risk markers. EP Europace 12(3):313–321. https://doi.org/10.1093/europace/eup431
Maki S, Ikeda H, Muro A, Yoshida N, Shibata A, Koga Y, Imaizumi T (1998) Predictors of sudden cardiac death in hypertrophic cardiomyopathy. Am J Cardiol 82(6):774–778
Maron BJ, Ackerman MJ, Nishimura RA, Pyeritz RE, Towbin JA, Udelson JE (2005) Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 45(8):1340–1345. https://doi.org/10.1016/j.jacc.2005.02.011
Ommen SR, Gersh BJ (2009) Sudden cardiac death risk in hypertrophic cardiomyopathy. Eur Heart J 30(21):2558–2559. doi:https://doi.org/10.1093/eurheartj/ehp307
Authors/Task Force m, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H, Additional C, O'Mahony C, Guidelines ESCCfP, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol Ç, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document R, Hasdai D, Ponikowski P, Achenbach S, Alfonso F, Basso C, Cardim NM, Gimeno JR, Heymans S, Holm PJ, Keren A, Kirchhof P, Kolh P, Lionis C, Muneretto C, Priori S, Salvador MJ, Wolpert C, Zamorano JL, Frick M, Aliyev F, Komissarova S, Mairesse G, Smajić E, Velchev V, Antoniades L, Linhart A, Bundgaard H, Heliö T, Leenhardt A, Katus HA, Efthymiadis G, Sepp R, Thor Gunnarsson G, Carasso S, Kerimkulova A, Kamzola G, Skouri H, Eldirsi G, Kavoliuniene A, Felice T, Michels M, Hermann Haugaa K, Lenarczyk R, Brito D, Apetrei E, Bokheria L, Lovic D, Hatala R, Garcia Pavía P, Eriksson M, Noble S, Srbinovska E, Özdemir M, Nesukay E, Sekhri N (2014) 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathyThe Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 35 (39):2733–2779. doi:https://doi.org/10.1093/eurheartj/ehu284
O’mahony C, Jichi F, Pavlou M, Monserrat L, Anastasakis A, Rapezzi C, Biagini E, Gimeno JR, Limongelli G, McKenna WJ (2013) A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J 35(30):2010–2020
O’mahony C, Jichi F, Ommen SR, Christiaans I, Arbustini E, Garcia-Pavia P, Cecchi F, Olivotto I, Kitaoka H, Gotsman I (2018) International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM). Circulation 137(10):1015–1023
Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, Epstein AE, Almquist AK, Daubert JP, Lawrenz T, Boriani G, Estes NA 3, Favale S, Piccininno M, Winters SL, Santini M, Betocchi S, Arribas F, Sherrid MV, Buja G, Semsarian C, Bruzzi P (2007) Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 298(4):405–412. https://doi.org/10.1001/jama.298.4.405
Spirito P, Autore C, Formisano F, Assenza GE, Biagini E, Haas TS, Bongioanni S, Semsarian C, Devoto E, Musumeci B, Lai F, Yeates L, Conte MR, Rapezzi C, Boni L, Maron BJ (2014) Risk of sudden death and outcome in patients with hypertrophic cardiomyopathy with benign presentation and without risk factors. Am J Cardiol 113(9):1550–1555. https://doi.org/10.1016/j.amjcard.2014.01.435
Adamczak DM, Oko-Sarnowska Z (2018) Sudden cardiac death in hypertrophic cardiomyopathy. Cardiol Rev 26(3):145–151. https://doi.org/10.1097/crd.0000000000000184
Rowin EJ, Maron MS (2016) The role of cardiac MRI in the diagnosis and risk stratification of hypertrophic cardiomyopathy. Arrhyth Electrophysiol Rev 5(3):197–202. https://doi.org/10.15420/aer.2016:13:3
Olivotto I, Maron MS, Autore C, Lesser JR, Rega L, Casolo G, De Santis M, Quarta G, Nistri S, Cecchi F, Salton CJ, Udelson JE, Manning WJ, Maron BJ (2008) Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 52(7):559–566. https://doi.org/10.1016/j.jacc.2008.04.047
Doltra A, Amundsen BH, Gebker R, Fleck E, Kelle S (2013) Emerging concepts for myocardial late gadolinium enhancement MRI. Curr Cardiol Rev 9(3):185–190. https://doi.org/10.2174/1573403X113099990030
Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O’Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309(9):896–908. https://doi.org/10.1001/jama.2013.1363
Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S (2016) Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson 18(1):89. https://doi.org/10.1186/s12968-016-0308-4
Kuruvilla S, Adenaw N, Katwal AB, Lipinski MJ, Kramer CM, Salerno M (2014) Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis. Circul Cardiovasc Imaging 7(2):250–258. https://doi.org/10.1161/circimaging.113.001144
Weng Z, Yao J, Chan RH, He J, Yang X, Zhou Y, He Y (2016) Prognostic value of LGE-CMR in HCM: a meta-analysis. JACC Cardiovasc imaging 9(12):1392–1402. https://doi.org/10.1016/j.jcmg.2016.02.031
Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ (2002) Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 40(12):2156–2164
Green JJ, Berger JS, Kramer CM, Salerno M (2012) Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imag 5(4):370–377. https://doi.org/10.1016/j.jcmg.2011.11.021
Ismail TF, Jabbour A, Gulati A, Mallorie A, Raza S, Cowling TE, Das B, Khwaja J, Alpendurada FD, Wage R, Roughton M, McKenna WJ, Moon JC, Varnava A, Shakespeare C, Cowie MR, Cook SA, Elliott P, O’Hanlon R, Pennell DJ, Prasad SK (2014) Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy. Heart 100(23):1851–1858. https://doi.org/10.1136/heartjnl-2013-305471
AlJaroudi WA, Flamm SD, Saliba W, Wilkoff BL, Kwon D (2013) Role of CMR imaging in risk stratification for sudden cardiac death. JACC Cardiovasc Imaging 6(3):392–406. https://doi.org/10.1016/j.jcmg.2012.11.011
Green JJ, Berger JS, Kramer CM, Salerno M (2012) Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 5(4):370–377. https://doi.org/10.1016/j.jcmg.2011.11.021
Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, Mahon NG, McKenna WJ (2000) Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 36(7):2212–2218
Basso C, Thiene G, Corrado D, Buja G, Melacini P, Nava A (2000) Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia. Human Pathol 31(8):988–998. https://doi.org/10.1053/hupa.2000.16659
Shiozaki AA, Senra T, Arteaga E, Martinelli Filho M, Pita CG, Avila LF, Parga Filho JR, Mady C, Kalil-Filho R, Bluemke DA, Rochitte CE (2013) Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy. J Cardiovasc Comput Tomogr 7(3):173–181. https://doi.org/10.1016/j.jcct.2013.04.002
Briasoulis A, Mallikethi-Reddy S, Palla M, Alesh I, Afonso L (2015) Myocardial fibrosis on cardiac magnetic resonance and cardiac outcomes in hypertrophic cardiomyopathy: a meta-analysis. Heart 101(17):1406–1411. https://doi.org/10.1136/heartjnl-2015-307682
Chan RH, Maron BJ, Olivotto I, Pencina MJ, Assenza GE, Haas T, Lesser JR, Gruner C, Crean AM, Rakowski H, Udelson JE, Rowin E, Lombardi M, Cecchi F, Tomberli B, Spirito P, Formisano F, Biagini E, Rapezzi C, De Cecco CN, Autore C, Cook EF, Hong SN, Gibson CM, Manning WJ, Appelbaum E, Maron MS (2014) Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 130(6):484–495. doi:https://doi.org/10.1161/circulationaha.113.007094
Chan RH, Maron BJ, Olivotto I, Pencina MJ, Assenza GE, Haas T, Lesser JR, Gruner C, Crean AM, Rakowski H, Udelson JE, Rowin E, Lombardi M, Cecchi F, Tomberli B, Spirito P, Formisano F, Biagini E, Rapezzi C, De Cecco CN, Autore C, Cook EF, Hong SN, Gibson CM, Manning WJ, Appelbaum E, Maron MS (2014) Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 130(6):484–495. https://doi.org/10.1161/circulationaha.113.007094
O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, Webb J, Kulkarni M, Dawson D, Sulaibeekh L, Chandrasekaran B, Bucciarelli-Ducci C, Pasquale F, Cowie MR, McKenna WJ, Sheppard MN, Elliott PM, Pennell DJ, Prasad SK (2010) Prognostic Significance of Myocardial Fibrosis in Hypertrophic Cardiomyopathy. J Am Coll Cardiol 56(11):867–874. doi:https://doi.org/10.1016/j.jacc.2010.05.010
Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ (2005) Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy. J Am Coll Cardiol 45(5):697–704. https://doi.org/10.1016/j.jacc.2004.11.043
Doesch C, Tulumen E, Akin I, Rudic B, Kuschyk J, El-Battrawy I, Becher T, Budjan J, Smakic A, Schoenberg SO, Borggrefe M, Papavassiliu T (2017) Incremental benefit of late gadolinium cardiac magnetic resonance imaging for risk stratification in patients with hypertrophic cardiomyopathy. Sci Rep 7(1):6336. https://doi.org/10.1038/s41598-017-06533-0
Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, Bos JM, Tajik AJ, Valeti US, Nishimura RA (2009) Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circulation 109:854026
Kwon DH, Smedira NG, Rodriguez ER, Tan C, Setser R, Thamilarasan M, Lytle BW, Lever HM, Desai MY (2009) Cardiac magnetic resonance detection of myocardial scarring in hypertrophic cardiomyopathy: correlation with histopathology and prevalence of ventricular tachycardia. J Am Coll Cardiol 54(3):242–249. https://doi.org/10.1016/j.jacc.2009.04.026
Amano Y, Kitamura M, Tachi M, Takeda M, Mizuno K, Kumita S (2014) Delayed enhancement magnetic resonance imaging in hypertrophic cardiomyopathy with Basal septal hypertrophy and preserved ejection fraction: relationship with ventricular tachyarrhythmia. J Comput Assist Tomogr 38(1):67–71. https://doi.org/10.1097/RCT.0b013e3182a2fb01
Appelbaum E, Maron BJ, Adabag S, Hauser TH, Lesser JR, Haas TS, Riley AB, Harrigan CJ, Delling FN, Udelson JE, Gibson CM, Manning WJ, Maron MS (2012) Intermediate-signal-intensity late gadolinium enhancement predicts ventricular tachyarrhythmias in patients with hypertrophic cardiomyopathy. Circul Cardiovasc Imaging 5(1):78–85. https://doi.org/10.1161/circimaging.111.963819
Harris KM, Spirito P, Maron MS, Zenovich AG, Formisano F, Lesser JR, Mackey-Bojack S, Manning WJ, Udelson JE, Maron BJ (2006) Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy. Circulation 114(3):216–225
Jiang M, Wang Z, Su X, Gong X, Pu J, Wu L, Liu C, Yao Q, Kong L, Xu J, He B (2018) The Significance of Interstitial Fibrosis on Left Ventricular Function in Hypertensive versus Hypertrophic Cardiomyopathy. Sci Rep 8(1):9995. https://doi.org/10.1038/s41598-018-27049-1
Ellims AH, Iles LM, Ling L-h, Hare JL, Kaye DM, Taylor AJ (2012) Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction. J Cardiovasc Magn Reson 14(1):76–76. https://doi.org/10.1186/1532-429X-14-76
Maron BJ, Rowin EJ, Udelson JE, Maron MS (2018) Clinical spectrum and management of heart failure in hypertrophic cardiomyopathy. JACC Heart Fail 6(5):353–363. https://doi.org/10.1016/j.jchf.2017.09.011
Amano Y, Kitamura M, Takano H, Yanagisawa F, Tachi M, Suzuki Y, Kumita S, Takayama M (2018) Cardiac MR imaging of hypertrophic cardiomyopathy: techniques, findings, and clinical relevance. Magn Reson Med Sci 17(2):120–131. https://doi.org/10.2463/mrms.rev.2017-0145
Funada A, Kanzaki H, Noguchi T, Morita Y, Sugano Y, Ohara T, Hasegawa T, Hashimura H, Ishibashi-Ueda H, Kitakaze M, Yasuda S, Ogawa H, Anzai T (2016) Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction. Heart Vessels 31(5):758–770. https://doi.org/10.1007/s00380-015-0670-4
Parsai C, O’Hanlon R, Prasad SK, Mohiaddin RH (2012) Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies. J Cardiovasc Magn Reson 14:54. https://doi.org/10.1186/1532-429x-14-54
Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ (2000) Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart 84(5):476–482
Jellis CL, Kwon DH (2014) Myocardial T1 mapping: modalities and clinical applications. Cardiovasc Diagn Ther 4(2):126–137. https://doi.org/10.3978/j.issn.2223-3652.2013.09.03
Puntmann VO, Peker E, Chandrashekhar Y, Nagel E (2016) T1 mapping in characterizing myocardial disease: a comprehensive review. Circul Res 119(2):277–299. https://doi.org/10.1161/circresaha.116.307974
Taylor AJ, Salerno M, Dharmakumar R, Jerosch-Herold M (2016) T1 mapping: basic techniques and clinical applications. JACC Cardiovasc Imaging 9(1):67–81. https://doi.org/10.1016/j.jcmg.2015.11.005
Spach MS, Boineau JP (1997) Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysiol 20(2 Pt 2):397–413
Chen Z, Sohal M, Voigt T, Sammut E, Tobon-Gomez C, Child N, Jackson T, Shetty A, Bostock J, Cooklin M, O’Neill M, Wright M, Murgatroyd F, Gill J, Carr-White G, Chiribiri A, Schaeffter T, Razavi R, Rinaldi CA (2015) Myocardial tissue characterization by cardiac magnetic resonance imaging using T1 mapping predicts ventricular arrhythmia in ischemic and non-ischemic cardiomyopathy patients with implantable cardioverter-defibrillators. Heart Rhythm 12(4):792–801. https://doi.org/10.1016/j.hrthm.2014.12.020
McLellan AJ, Ellims AH, Prabhu S, Voskoboinik A, Iles LM, Hare JL, Kaye DM, Macciocca I, Mariani JA, Kalman JM (2016) Diffuse ventricular fibrosis on cardiac magnetic resonance imaging associates with ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Cardiovasc Electrophys 27(5):571–580
Kim PK, Hong YJ, Im DJ, Suh YJ, Park CH, Kim JY, Chang S, Lee H-J, Hur J, Kim YJ, Choi BW (2017) Myocardial T1 and T2 mapping: techniques and clinical applications. Korean J Radiol 18(1):113–131. https://doi.org/10.3348/kjr.2017.18.1.113
Ellims AH, Iles LM, Ling L-h, Chong B, Macciocca I, Slavin GS, Hare JL, Kaye DM, Marasco SF, McLean CA, James PA, du Sart D, Taylor AJ (2014) A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype. Eur Heart J 15(10):1108–1116. https://doi.org/10.1093/ehjci/jeu077
Sado DM, Flett AS, Banypersad SM, White SK, Maestrini V, Quarta G, Lachmann RH, Murphy E, Mehta A, Hughes DA, McKenna WJ, Taylor AM, Hausenloy DJ, Hawkins PN, Elliott PM, Moon JC (2012) Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart 98(19):1436–1441. https://doi.org/10.1136/heartjnl-2012-302346
Avanesov M, Munch J, Weinrich J, Well L, Saring D, Stehning C, Tahir E, Bohnen S, Radunski UK, Muellerleile K, Adam G, Patten M, Lund G (2017) Prediction of the estimated 5-year risk of sudden cardiac death and syncope or non-sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy using late gadolinium enhancement and extracellular volume CMR. Eur Radiol 27(12):5136–5145. https://doi.org/10.1007/s00330-017-4869-x
Maron MS (2012) Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 14(1):13–13. https://doi.org/10.1186/1532-429X-14-13
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Raiker, N., Vullaganti, S., Collins, J.D. et al. Myocardial tissue characterization by gadolinium-enhanced cardiac magnetic resonance imaging for risk stratification of adverse events in hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 36, 1147–1156 (2020). https://doi.org/10.1007/s10554-020-01808-6
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DOI: https://doi.org/10.1007/s10554-020-01808-6