Assessment of Myocardial Fibrosis in Hypertrophic Cardiomyopathy by Cardiac Magnetic Resonance: Modalities and Clinical Applications

Carla Contaldi

Abstract


Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease caused by mutations in sarcomeric contractile proteins, characterized by cardiomyocytes disarray, interstitial fibrosis, increased arteriolar wall thickness and scarring.

Fibrosis could represent a substrate for the generation of malignant ventricular tachyarrhythmias, which represent the current pathway for sudden cardiac death and is responsible for passive diastolic dysfunction, that is the leading cause of dyspnea.

The aim of this review is to depict the increasingly role of cardiac magnetic resonance (CMR) for assessment of myocardial fibrosis in HCM. This article will briefly review the current status of the novel CMR techniques (the Late Gadolinium Enhancement and the emerging T1 mapping) for identification, characterization and quantization of myocardial fibrosis in HCM.

In addition, this review will discuss the most recent acquisition techniques, the new parameters and their possible clinical utility in diagnosis, therapeutic management and prognosis in HCM.


Keywords


: Myocardial fibrosis; Late Gadolinium Enhancement; T1-mapping; Hypertrophic cardiomyopathy

References


Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation 1995; 92:785-89

Braunwald E. Hypertrophic cardiomyopathy – continued progress. N Engl J Med 1989; 320:800-34

McKenna WJ, Spirito P, Desnos M, Dubourg O, Komajda M. Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart 1997; 77:130-32

Cannon RO, Rosing DR, Maron BJ, Leon MB, Bonow RO, Watson RM, Epstein SE. Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures. Circulation 1985; 71:234-43

Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: interrelations of clinical manifestations, pathophysiology, and therapy. N Engl J Med 1987; 316:780-89, 844-52

Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol 2000; 35:36-44

Maceira AM, Barba J, Beloqui O, Diez J. Ultrasonic backscatter and diastolic function in hypertensive patients. Hypertension 2002; 40:239-43

Kozakova M, Buralli S, Palombo C, Bernini G, Moretti A, Favilla S, Taddei S, Salvetti A. Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Hypertension 2003; 41:230-36

Lombardi R, Betocchi S, Losi MA, Tocchetti CG, Aversa M, Miranda M et al. Myocardial collagen turnover in hypertrophic cardiomyopathy. Circulation 2003; 108:1455-60

Burlew BS, Weber KT. Cardiac fibrosis as a cause of diastolic dysfunction. Herz 2002; 27:92-98

Patel R, Nagueh SF, Tsybouleva N, Abdellatif M, Lutucuta S, Kopelen HA et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2001; 104:317-24

Lombardi R., Rodriguez G, Chen SN, Ripplinger CM, Li W, Chen J et al. Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy through Thiol-Sensitive Mechanisms. Circulation 2009; 119:1398-407 doi: 10.1161/CIRCULATIONAHA.108.790501

Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P et al. Myocardial Fibrosis as an Early Manifestation of Hypertrophic Cardiomyopathy. N Engl J Med 2010; 363: 552–63 doi: 10. 1161 /CIRCIMAGING .112. 000333

Ho CY, Abbasi SA, Neilan TG, Shah RV, Chen Y, Heydari B et al. T1 Measurements Identify Extracellular Volume Expansion in HypertrophicCardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy. Circ Cardiovasc Imaging 2013; 6:415-22 doi: 10.1161/CIRCIMAGING.112. 000333

Bondarenko O, Beek AM, Hofman MB, Kühl HP, Twisk JW, van Dockum WG et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson 2005 ; 7:481-85

Croisille P, Revel D, Saeed M. Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to bedside. Eur Radiol 2006; 16:1951-63

Judd RM, Atalay MK, Rottman GA, Zerhouni EA. Effects of myocardial water exchange on T1 enhancement during bolus administration of MR contrast agents. Magn Reson Med 1995; 33:215-23

Kim RJ, Chen EL, Lima JA, Judd RM. Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction. Circulation 1996; 94:3318-26

Gottlieb I, Macedo R, Bluemke DA, Lima JA. Magnetic resonance imaging in the evaluation of non-ischemic cardiomyopathies: current applications and future perspective. Heart Fail Rev 2006; 11:313-23

Wu E, Judd RM, Vargas JD, Caputo GR, O'Sullivan M, Cheitlin MD, Higgins CB. MR imaging of the myocardium using nonionic contrast medium: signal- intensity changes in patients with subacute myocardial infarction. AJR Am J Roentgenol 1993; 160:963-70

Moon JC, Reed E, Sheppard MN, Elkington AG, Ho SY, Burke M et al. The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 43:2260–64

Contaldi C, Imbriaco M, Alcidi G, Ponsiglione A, Santoro C, Puglia M, Barbuto L, Cuocolo A, Trimarco B, Galderisi M. Assessment of the relationships between left ventricular filling pressures and longitudinal dysfunction with myocardial fibrosis in uncomplicated hypertensive patients. Int J Cardiol. 2016 Jan 1;202:84-6. doi:10.1016/j.ijcard.2015.08.153

O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R et al. Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56:867-74 doi: 10.1016/j.jacc.2010.05.010

Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P. Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail 2010; 3:51-8 doi: 10. 1161 /CIRCHEARTFAILURE.109.854026

Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2002; 40:2156-64

Maron MS, Hauser TH, Dubrow E, Horst TA, Kissinger KV, Udelson JE, Manning WJ. Right ventricular involvement in hypertrophic cardiomyopathy. Am J Cardiol 2007; 100:1293-8

Aquaro GD, Positano V, Pingitore A, Strata E, Di Bella G, Formisano F, Spirito P, Lombardi M. Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2010; 12:21 doi: 10.1186/1532-429X-12-21

Schmidt A, Azevedo CF, Cheng A, Gupta SN, Bluemke DA, Foo TK et al. Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction. Circulation 2007; 115:2006-14

Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, Luu TM et al. Characterization of the peri-infarct zone by contrast enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation 2006; 114:32-9

Flett AS, Hasleton J, Cook C, Hausenloy D, Quarta G, Ariti C, Muthurangu V, Moon JC. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. JACC Cardiovascular imaging 2011; 4:150-6 doi: 10.1016 /j.jcmg.2010.11.015

Harrigan CJ, Peters DC, Gibson CM, Maron BJ, Manning WJ, Maron MS, Appelbaum E. Hypertrophic cardiomyopathy: quantification of late gadolinium enhancement with contrast-enhanced cardiovascular MR imaging. Radiology 2011; 258:128-33 doi: 10.1148/radiol.10090526

Mikami Y, Kolman L, Joncas SX, Stirrat J, Scholl D, Rajchl M et al. Accuracy and reproducibility of semiautomated late gadolinium enhancement quantification techniques inpatients with hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2014; 16:85

Salerno M, Kramer CM. Advances in parametric mapping with CMR imaging. JACC Cardiovasc Imaging 2013; 6:806-22 doi: 10.1016/j.jcmg.2013.05.005

Look DC, Locker DR. Time saving in measurement of NMR and EPR relaxation times. Rev Sci Instrum 1970; 41:250-51

Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004; 52:141-146

Messroghli DR, Pleinn S, Higgins DM, Walters K, Jones TR, Ridgway JP, Sivananthan MU. Human myocardium: single-breath-hold MR T1 mapping with high study. Radiology 2006; 238:1004-23

Messroghli DR, Greiser A, Frohlich M, Dietz R, Schulz-Menger J. Optimization and validation of a fully- integrated pulse sequence for modified look-locker inversion-recovery (MOLLI) T1 mapping of the heart. J Magn Reson Imaging 2007; 26:1081-86

Piechnik SK, Ferreira VM, Dall’Armellina E, Cochlin LE, Greiser A, Neubauer S, Robson MD. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heart beat breathhold. J Cardiovasc Magn Reson 2010; 19:69 doi: 10.1186/1532-429X-12-69.

Chow K, Flewitt JA, Green JD, Pagano JJ, Friedrich MG, Thompson RB. Saturation recovery single-shot acquisition (SASHA) for myocardial T1 mapping. Magn Reson Med 2014; 71:2082–95 doi: 10.1002/mrm.24878

Messroghli DR, Walters K, Plein S, Sparrow P, Friedrich MG, Ridgway JP, Sivananthan MU. Myocardial T1 mapping: application to patients with acute and chronic myocardial infarction. Magn Reson Med. 2007; 58:34-40

Dass S, Suttie JJ, Piechnik SK, Ferreira VM, Holloway CJ, Banerjee R et al. Myocardial tissue characterization using magnetic resonance non-contrast t1 mapping in hypertrophic and dilated cardiomyopathy. Circ Cardiovasc Imaging 2012; 5:726–33 doi: 10.1161/ CIRCIMAGING.112.976738

Kehr E, Sono M, Chugh SS, Jerosch-Herold M. Gadolinium-enhanced magnetic resonance imaging for detection and quantification of fibrosis in human myocardium in vitro. Int J Cardiovasc Imaging 2008; 24:61-68

Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN et al. Evaluation of Diffuse Myocardial Fibrosis in Heart Failure With Cardiac Magnetic Resonance Contrast- Enhanced T1 mapping. J Am Coll Cardiol 2008; 52:1574-80 doi: 10.1016/j.jacc.2008.06.049

Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013; 15:92 doi: 10.1186/1532-429X-15-92

Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 2010; 122:138-144 doi: 10.1161/CIRCULATIONAHA.109.930636

White SK, Sado DM, Fontana M, Banypersad SM, Maestrini V, Flett AS, Piechnik SK, Robson MD, Hausenloy DJ, Sheikh AM, Hawkins PN, Moon JC. T1 mapping for myocardial extracellular volume measurement by CMR: bolus only versus primed infusion technique. JACC Cardiovasc Imaging 2013; 6:955-62 doi: 10.1016/j.jcmg.2013.01.011.

Małek ŁA, Werys K, Kłopotowski M, Śpiewak M, Miłosz-Wieczorek B, Mazurkiewicz Ł, Petryka-Mazurkiewicz J, Marczak M, Witkowski A. Native T1-mapping for non-contrast assessment of myocardial fibrosis in patients with hypertrophic cardiomyopathy-comparison with late enhancement quantification. Magn Reson Imaging 2015; 33:718-24 doi: 10.1016/j.mri.2015.04.001

Ellims AH, Iles LM, Ling LH, Chong B, Macciocca I, Slavin GS et al. A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype. Eur Heart J Cardiovasc Imaging 2014; 15:1108-16 doi: 10.1093/ ehjci/jeu077

Fontana M1, White SK, Banypersad SM, Sado DM, Maestrini V, Flett AS, Piechnik SK, Neubauer S, Roberts N, Moon JC. Comparison of T1 mapping techniques for ECV quantification. Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR. J Cardiovasc Magn Reson 2012; 14:88 doi: 10.1186/1532-429X-14-88

Miller CA, Naish JH, Bishop P, Coutts G, Clark D, Zhao S, Ray SG, Yonan N, Williams SG, Flett AS, Moon JC, Greiser A, Parker GJ, Schmitt M. Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume. Circ Cardiovasc Imaging 2013; 6:373-83. doi: 10.1161/CIRCIMAGING.112.000192.

Puntmann VO, Voigt T, Chen Z, et al. Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. J Am Coll Cardiol Img 2013; 6:475–84 doi: 10.1016/j.jcmg.2012.08.019

Green JJ, Berger JS, Kramer CM, Salerno M. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 2012; 5:370-7 doi: 10.1016/j.jcmg.2011.11.021

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 doi: 10.1016/j.jacc.2007.11.071.

Rubinshtein R, Glockner JF, Ommen SR Araoz PA, Ackerman MJ, Sorajja P et all. Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patient with hypertrophic cardiomyopathy. Circ Heart Fail 2010; 3:51-58 doi: 10.1161/CIRCHEARTFAILURE.109.854026

O’Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R et al. Prognosic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56:867-74 doi: 10.1016/j.jacc.2010.05.010.

Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, Nassenstein K et al. Myocardial scar visualized by cardiac magnetic resonance imaging predicts major adverse cardiac events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2010; 56:875-87 doi: 10.1016/j.jacc.2010.05.007

Chan RH, Maron BJ, Olivotto I, Pencina MJ, Assenza GE, Haas T et al. Prognostic value of quantitative contrast enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 2014; 130: 484-95 doi: 10.1161/CIRCULATIONAHA.113.007094

Ismail TF, Jabbour A, Gulati A, Mallorie A, Raza S, Cowling TE et al. Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy. Heart 2014; 100: 1851-8 doi: 10.1136/heartjnl-2013-305471

Zhu Y, Park EA, Lee W, Kim HK, Chu A, Chung JW, Park JH. Extent of late gadolinium enhancement at right ventricular insertion points in patients with hypertrophic cardiomyopathy: relation with diastolic dysfunction. Eur Radiol. 2015; 25:1190-200 doi: 10.1007/s00330-014-3390-8

Austin BA, Tang WH, Rodriguez ER, Tan C, Flamm SD, Taylor DO, Starling RC, Desai MY. Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis. JACC Cardiovasc Imaging 2009; 2:1369-77 doi: 10.1016/j.jcmg.2009.08.008

Maron MS. Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Cardiovascular Magn Reson 2012; 14:13

Ichinose A, Otani H, Oikawa M, Takase K, Saito H, Shimokawa H, Takahashi S. MRI of cardiac sarcoidosis: basal and subepicardial localization of myocardial lesions and their effect on left ventricular function. AJR Am J Roentgenol 2008; 191:862-69

Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, Meine TJ, White JB, Elliott MD, Kim HW, Judd RM, Kim RJ. Detection of myocardial damage in patients with sarcoidosis. Circulation 2009; 120:1969-77 doi: 10.1161/CIRCULATIONAHA.109.851352

Wong TC, Chung J, Kellman P, Schelbert EB. Extracellular volume fraction is associated with B-type natriuretic peptide in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson.2014; 16(Suppl):331

Geske JB, McKie PM, Ommen SR, Sorajja P. B-type natriuretic Peptide and survival in hypertrophic cardiomyopathy. J Am Coll Cardiol 2013; 61:2456–60

van Ooij P, Allen BD, Contaldi C, Garcia J, Collins J, Carr J, Choudhury L, Bonow RO, Barker AJ, Markl M. 4D flow MRI and T1-Mapping: Assessment of altered cardiac hemodynamics and extracellular volume fraction in hypertrophic cardiomyopathy. J Magn Reson Imaging 2016; 43:107-14 doi: 10.1002/jmri.24962.

Hinojar R, Varma N, Child N, Goodman B, Jabbour A, Yu CY et al. T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy: Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study. Circ Cardiovasc Imaging 2015; 8:e003285. doi: 10 .1161/CIRCIMAGING. 115.003285

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 DOI: 10.17987/icfj.v2i1.4




DOI: https://doi.org/10.17987/icfj.v8i0.253


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