Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction
The presence of myocardial fibrosis is associated with worse clinical outcomes in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) sequences can detect regional, but not diffuse myocardial fibrosis. Post-contrast T1 mapping is an emerging CMR technique that may enable the non-invasive evaluation of diffuse myocardial fibrosis in HCM. The purpose of this study was to non-invasively detect and quantify diffuse myocardial fibrosis in HCM with CMR and examine its relationship to diastolic performance.
We performed CMR on 76 patients - 51 with asymmetric septal hypertrophy due to HCM and 25 healthy controls. Left ventricular (LV) morphology, function and distribution of regional myocardial fibrosis were evaluated with cine imaging and LGE. A CMR T1 mapping sequence determined the post-contrast myocardial T1 time as an index of diffuse myocardial fibrosis. Diastolic function was assessed by transthoracic echocardiography.
Regional myocardial fibrosis was observed in 84% of the HCM group. Post-contrast myocardial T1 time was significantly shorter in patients with HCM compared to controls, consistent with diffuse myocardial fibrosis (498 ± 80 ms vs. 561 ± 47 ms, p < 0.001). In HCM patients, post-contrast myocardial T1 time correlated with mean E/e’ (r = −0.48, p < 0.001).
Patients with HCM have shorter post-contrast myocardial T1 times, consistent with diffuse myocardial fibrosis, which correlate with estimated LV filling pressure, suggesting a mechanistic link between diffuse myocardial fibrosis and abnormal diastolic function in HCM.
- Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spirito P, Ten Cate FJ, Wigle ED, Spencer WH 3rd: 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, 42:1687–1713. CrossRef
- Maron BJ: Hypertrophic cardiomyopathy: a systematic review. JAMA 2002, 287:1308–1320. CrossRef
- Marian AJ, Roberts R: The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol 2001, 33:655–670. CrossRef
- Seidman JG, Seidman C: The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 2001, 104:557–567. CrossRef
- Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, Epstein AE, Almquist AK, Daubert JP, Lawrenz T, et al.: Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007, 298:405–412. CrossRef
- Fifer MA, Vlahakes GJ: Management of symptoms in hypertrophic cardiomyopathy. Circulation 2008, 117:429–439. CrossRef
- Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ: Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart 2000, 84:476–482. CrossRef
- Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA: Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 2011, 57:891–903. CrossRef
- Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM: The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000, 343:1445–1453. CrossRef
- Kim RJ, Judd RM: Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death? J Am Coll Cardiol 2003, 41:1568–1572. CrossRef
- O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, Webb J, Kulkarni M, Dawson D, Sulaibeekh L, et al.: Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 2010, 56:867–874. CrossRef
- Wilson JM, Villareal RP, Hariharan R, Massumi A, Muthupillai R, Flamm SD: Magnetic resonance imaging of myocardial fibrosis in hypertrophic cardiomyopathy. Tex Heart Inst J 2002, 29:176–180.
- Teraoka K, Hirano M, Ookubo H, Sasaki K, Katsuyama H, Amino M, Abe Y, Yamashina A: Delayed contrast enhancement of MRI in hypertrophic cardiomyopathy. Magn Reson Imaging 2004, 22:155–161. CrossRef
- Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, Bos JM, Tajik AJ, Valeti US, Nishimura RA, Gersh BJ: Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail 2010, 3:51–58. CrossRef
- 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, 40:2156–2164. CrossRef
- Noureldin RA, Liu S, Nacif MS, Judge DP, Halushka MK, Abraham TP, Ho C, Bluemke DA: The diagnosis of hypertrophic cardiomyopathy by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2012, 14:17. CrossRef
- Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ: Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 2008, 52:1574–1580. CrossRef
- Ng AC, Auger D, Delgado V, van Elderen SG, Bertini M, Siebelink HM, van der Geest RJ, Bonetti C, van der Velde ET, de Roos A, et al.: Association between diffuse myocardial fibrosis by cardiac magnetic resonance contrast-enhanced T mapping and subclinical myocardial dysfunction in diabetic patients: a pilot study. Circ Cardiovasc Imaging 2012, 5:51–59. CrossRef
- Amano Y, Takayama M, Kumita S: Contrast-enhanced myocardial T1-weighted scout (Look-Locker) imaging for the detection of myocardial damages in hypertrophic cardiomyopathy. J Magn Reson Imaging 2009, 30:778–784. CrossRef
- 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. CrossRef
- Taylor AJ, Al-Saadi N, Abdel-Aty H, Schulz-Menger J, Messroghli DR, Friedrich MG: Detection of acutely impaired microvascular reperfusion after infarct angioplasty with magnetic resonance imaging. Circulation 2004, 109:2080–2085. CrossRef
- Saranathan M, Rochitte CE, Foo TK: Fast, three-dimensional free-breathing MR imaging of myocardial infarction: a feasibility study. Magn Reson Med 2004, 51:1055–1060. CrossRef
- Maron MS: Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2012, 14:13. CrossRef
- Conte MR, Bongioanni S, Chiribiri A, Leuzzi S, Lardone E, Di Donna P, Pizzuti A, Luceri S, Cesarani F, Mabritto B, et al.: Late gadolinium enhancement on cardiac magnetic resonance and phenotypic expression in hypertrophic cardiomyopathy. Am Heart J 2011, 161:1073–1077. CrossRef
- Green JJ, Berger JS, Kramer CM, Salerno M: Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 2012, 5:370–377. CrossRef
- Maron MS, Appelbaum E, Harrigan CJ, Buros J, Gibson CM, Hanna C, Lesser JR, Udelson JE, Manning WJ, Maron BJ: Clinical profile and significance of delayed enhancement in hypertrophic cardiomyopathy. Circ Heart Fail 2008, 1:184–191. CrossRef
- Kasner M, Westermann D, Lopez B, Gaub R, Escher F, Kuhl U, Schultheiss HP, Tschope C: Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction. J Am Coll Cardiol 2011, 57:977–985. CrossRef
- Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH 3rd, Zoghbi WA, Quinones MA: Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation 1999, 99:254–261. CrossRef
- Geske JB, Sorajja P, Nishimura RA, Ommen SR: Evaluation of left ventricular filling pressures by Doppler echocardiography in patients with hypertrophic cardiomyopathy: correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation 2007, 116:2702–2708. CrossRef
- Matsumura Y, Elliott PM, Virdee MS, Sorajja P, Doi Y, McKenna WJ: Left ventricular diastolic function assessed using Doppler tissue imaging in patients with hypertrophic cardiomyopathy: relation to symptoms and exercise capacity. Heart 2002, 87:247–251. CrossRef
- Nagueh SF, Bierig SM, Budoff MJ, Desai M, Dilsizian V, Eidem B, Goldstein SA, Hung J, Maron MS, Ommen SR, Woo A: American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with hypertrophic cardiomyopathy: Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, and Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr 2011, 24:473–498. CrossRef
- Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, McMahon EG, Delyani JA: Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002, 283:H1802–1810.
- Messroghli DR, Nordmeyer S, Dietrich T, Dirsch O, Kaschina E, Savvatis K, Oh-I D, Klein C, Berger F, Kuehne T: Assessment of diffuse myocardial fibrosis in rats using small-animal Look-Locker inversion recovery T1 mapping. Circ Cardiovasc Imaging 2011, 4:636–640. CrossRef
- Jellis C, Wright J, Kennedy D, Sacre J, Jenkins C, Haluska B, Martin J, Fenwick J, Marwick TH: Association of imaging markers of myocardial fibrosis with metabolic and functional disturbances in early diabetic cardiomyopathy. Circ Cardiovasc Imaging 2011, 4:693–702. CrossRef
- Sparrow P, Messroghli DR, Reid S, Ridgway JP, Bainbridge G, Sivananthan MU: Myocardial T1 mapping for detection of left ventricular myocardial fibrosis in chronic aortic regurgitation: pilot study. AJR Am J Roentgenol 2006, 187:W630–635. CrossRef
- Chan W, Duffy SJ, White DA, Gao XM, Du XJ, Ellims AH, Dart AM, Taylor AJ: Acute left ventricular remodeling following myocardial infarction: coupling of regional healing with remote extracellular matrix expansion. JACC Cardiovasc Imaging 2012, 5:884–893. CrossRef
- Abdel-Aty H, Simonetti O, Friedrich MG: T2-weighted cardiovascular magnetic resonance imaging. J Magn Reson Imaging 2007, 26:452–459. CrossRef
- Ferreira VM, Piechnik SK, Dall'armellina E, Karamitsos TD, Francis JM, Choudhury RP, Friedrich MG, Robson MD, Neubauer S: Non-contrast T1-mapping detects acute myocardial edema with high diagnostic accuracy: a comparison to T2-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2012, 14:42. CrossRef
- Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Journal of Cardiovascular Magnetic Resonance
- Online Date
- October 2012
- Online ISSN
- BioMed Central
- Additional Links
- Hypertrophic cardiomyopathy
- Magnetic resonance imaging
- Myocardial fibrosis
- T1 mapping