T1 mapping in dilated cardiomyopathy with cardiac magnetic resonance: quantification of diffuse myocardial fibrosis and comparison with endomyocardial biopsy.

AIM The aim of this study was to determine the value of extracellular volume fraction (ECV) for the non-invasive assessment of diffuse myocardial fibrosis (MF) in different stages of systolic left ventricular (LV) dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy. BACKGROUND Non-invasive ECV assessment using cardiovascular magnetic resonance (CMR) T1 mapping reflects diffuse MF in patients with severe DCM, but earlier stages of DCM with mild LV functional impairment have not been investigated yet. METHODS Forty-five subjects with mild functional impairment and LV dilation ['early DCM', ejection fraction (EF) 45-55%], 29 with LV dysfunction and volume dilatation ('DCM', EF <45%) and 56 healthy volunteers (controls) underwent standard CMR imaging, late gadolinium enhancement (LGE) and T1 mapping for the calculation of ECV. The collagen volume fraction (CVF) was quantified histologically from endomyocardial biopsies of 24 DCM patients out of the study cohort. RESULTS The ECV between 'early DCM' (25 ± 4%), 'DCM' (27 ± 4%), and controls (23 ± 3; P < 0.05 for all) differed significantly. There was a weak inverse correlation between ECV and EF (r = -0.35; P < 0.01). A strong correlation between ECV and CVF could be detected (r = 0.85; P = 0.01). The cut-off value for ECV to differentiate between healthy myocardium and DCM was 26% (specificity 91.1%, sensitivity 62.1%, area under the curve 0.8, P < 0.0001). ECV is already elevated at early stages of functional impairment, whereby an overlap between early DCM and controls is present. But 31% of the early DCM patients had an ECV fraction above the mean ±2 SD ECV of controls. CONCLUSIONS ECV measurement with CMR reflects myocardial collagen content in DCM. Therefore, CMR-based assessment of ECV may have the potential to serve as a non-invasive tool for the quantification of diffuse MF in order to monitor therapy response and aid risk stratification in different stages of DCM.

[1]  D. Bluemke,et al.  Modified look-locker inversion recovery T1 mapping indices: assessment of accuracy and reproducibility between magnetic resonance scanners , 2013, Journal of Cardiovascular Magnetic Resonance.

[2]  P. Kellman,et al.  Association Between Extracellular Matrix Expansion Quantified by Cardiovascular Magnetic Resonance and Short-Term Mortality , 2012, Circulation.

[3]  Salim Yusuf,et al.  Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. , 1991, The New England journal of medicine.

[4]  David M Higgins,et al.  Human myocardium: single-breath-hold MR T1 mapping with high spatial resolution--reproducibility study. , 2006, Radiology.

[5]  Andrew S Flett,et al.  Comprehensive Validation of Cardiovascular Magnetic Resonance Techniques for the Assessment of Myocardial Extracellular Volume , 2013, Circulation. Cardiovascular imaging.

[6]  C. Higgins,et al.  Delayed Contrast Enhancement on MR Images of Myocardium , 2011 .

[7]  K. Weber,et al.  Cardiac Fibrosis as a Cause of Diastolic Dysfunction , 2002, Herz.

[8]  James O. Mudd,et al.  T1 Mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. , 2012, Radiology.

[9]  Nader Moazami,et al.  Conduction Remodeling in Human End-Stage Nonischemic Left Ventricular Cardiomyopathy , 2012, Circulation.

[10]  Andrew S Flett,et al.  Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease , 2012, Heart.

[11]  Arantxa González,et al.  Losartan-Dependent Regression of Myocardial Fibrosis Is Associated With Reduction of Left Ventricular Chamber Stiffness in Hypertensive Patients , 2002, Circulation.

[12]  David A Bluemke,et al.  T1 mapping of the myocardium: Intra-individual assessment of the effect of field strength, cardiac cycle and variation by myocardial region , 2012, Journal of Cardiovascular Magnetic Resonance.

[13]  A. Hoes,et al.  Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. , 2005, European heart journal.

[14]  J. S. Janicki,et al.  Myocardial fibrosis: functional significance and regulatory factors. , 1993, Cardiovascular research.

[15]  Michael Jerosch-Herold,et al.  Quantification of Diffuse Myocardial Fibrosis and Its Association With Myocardial Dysfunction in Congenital Heart Disease , 2010, Circulation. Cardiovascular imaging.

[16]  David M Higgins,et al.  Modified Look‐Locker inversion recovery (MOLLI) for high‐resolution T1 mapping of the heart , 2004, Magnetic resonance in medicine.

[17]  P. Sanders,et al.  Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography , 2011, Journal of Cardiovascular Magnetic Resonance.

[18]  M. Pfeffer,et al.  Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme , 2003, The Lancet.

[19]  Pierre Croisille,et al.  Assessment of myocardial fibrosis with cardiovascular magnetic resonance. , 2011, Journal of the American College of Cardiology.

[20]  Sandeep N. Gupta,et al.  Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. , 2008, Journal of the American College of Cardiology.

[21]  L. A. Bonet,et al.  ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 , 2012, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[22]  H. Katus,et al.  Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy , 2010, Heart.

[23]  M. Schieber,et al.  Comparative Evaluation of Left and Right Ventricular Endomyocardial Biopsy: Differences in Complication Rate and Diagnostic Performance , 2010, Circulation.

[24]  Reza Razavi,et al.  Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. , 2013, JACC. Cardiovascular imaging.

[25]  Y. Kim,et al.  Patterns of late gadolinium enhancement are associated with ventricular stiffness in patients with advanced non‐ischaemic dilated cardiomyopathy † , 2009, European journal of heart failure.

[26]  Jeanette Schulz-Menger,et al.  An open-source software tool for the generation of relaxation time maps in magnetic resonance imaging , 2010, BMC Medical Imaging.

[27]  David D Spragg,et al.  Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy , 2004, Circulation research.

[28]  A. Taylor,et al.  Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. , 2012, European heart journal cardiovascular Imaging.

[29]  B. Pitt.  Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). , 1996, The American journal of cardiology.

[30]  Eloisa Arbustini,et al.  Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. , 2007, European heart journal.

[31]  M. Hayward,et al.  Equilibrium Contrast Cardiovascular Magnetic Resonance for the Measurement of Diffuse Myocardial Fibrosis: Preliminary Validation in Humans , 2010, Circulation.

[32]  P. Kellman,et al.  Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. , 2012, European heart journal.

[33]  C. Rochitte,et al.  Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis in patients with severe aortic valve disease: Correlation with quantitative histopathology. , 2009, American heart journal.

[34]  L. Mestroni,et al.  Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. , 1999, European heart journal.

[35]  Michael Jerosch-Herold,et al.  Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy. , 2008, American journal of physiology. Heart and circulatory physiology.

[36]  P. Gallagher,et al.  Interstitial fibrosis in the dilated non-ischaemic myocardium , 2003, Heart.

[37]  S. Chugh,et al.  Gadolinium-enhanced magnetic resonance imaging for detection and quantification of fibrosis in human myocardium in vitro , 2007, The International Journal of Cardiovascular Imaging.

[38]  Titus Kuehne,et al.  Assessment of Diffuse Myocardial Fibrosis in Rats Using Small-Animal Look-Locker Inversion Recovery T1 Mapping , 2011, Circulation. Cardiovascular imaging.