International Journal of Cardiology 180 (2015) 111–113
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Prognostic value of late gadolinium enhancement in cardiomyopathy: Causative risk factor or surrogate marker? Peter Alter a,⁎, Jens H. Figiel b a b
University of Marburg, Internal Medicine, Germany University of Marburg, Radiology, Germany
a r t i c l e
i n f o
Article history: Received 30 October 2014 Accepted 23 November 2014 Available online 25 November 2014 Keywords: Late gadolinium enhancement Cardiac magnetic resonance Risk factor Prognosis Dilated cardiomyopathy Heart failure
Assessment of late gadolinium enhancement (LGE) is an integral part of CMR examinations for evaluating myocardial morphology. Occurrence of LGE relies on a prolonged myocardial contrast agent deposition that is used for image acquisition. LGE is a robust diagnostic criterion to delineate postinfarct scar in coronary artery disease. In contrast, causes and consequences of LGE are much less characterized in cardiomyopathies. Although fibrosis was related to LGE in hypertrophic cardiomyopathy [1], this association cannot be generalized. Every alteration (increase) of the interstitial space of arbitrary cause appears to bear a potential source of LGE. For further interpretation, type, pattern, intensity, localization, and duration of LGE need to be taken into account. Separately distributed midwall or transmural spots are typically observed in myocarditis, although a streaky-like midwall pattern, as usually known from chronic dilated cardiomyopathy, can also occur (Fig. 1). Besides this limited diagnostic specificity, also the sensitivity of the method is limited and appears to depend on the severity of disease, i.e. the extent of myocytolysis, necrosis, and edema [2]. The absence of CMR criteria does not exclude myocarditis (Fig. 2). In healed myocarditis and other reversible myocardial injuries, LGE is of transient nature. For instance, LGE, facultatively occurring in the acute stage of Takotsubo syndrome,
disappears in parallel to the decline of ventricular ballooning [3]. Taking the longer half-life of collagen degradation and the observed short-term reversibility of LGE into account, it can be deduced that LGE cannot equal fibrosis per se. Studies using methods of T1 mapping showed an inverse correlation of postcontrast T1 times and myocardial fibrosis as defined by histology [4]. T1 times were shorter in cardiomyopathy with than without LGE, and longest in controls. Increased noncontrast T1 times were correlated with circumferential strain and also observed in myocardial segments unaffected by LGE [5]. Quantification of T1 times appears to be superior to LGE for detecting fibrosis. Other factors involved in the appearance of LGE should be considered. Increased myocardial fibrosis is known to be associated with unfavorable prognostic consequences, e.g. an increased arrhythmia risk, myocardial ischemia and further adverse remodeling. In parallel, several studies were suggestive of adverse prognostic influences of LGE. It was shown that LGE is associated with a worse outcome in dilated cardiomyopathy, but LGE was not an independent predictor by multivariate analysis [6]. In the thorough study by Rodríguez-Capitán et al., the presence of LGE was not associated with an adverse outcome in patients with dilated cardiomyopathy [7], which also argues against a one-toone relation of LGE and fibrosis. The question arises, whether LGE is indeed a causative risk factor or a surrogate marker? It was previously shown, that LGE is associated with increased left ventricular wall stress in dilated cardiomyopathy [8]. It is supposed that increased wall stress leads to a higher interstitial contrast agent deposition or an impaired redistribution into the vasculature, which causes appearance of LGE. Wall stress is predominantly determined by ventricular volumes, myocardial mass and the transmural pressure gradient [9]. Ventricular dilatation leads to an increase of wall stress when myocardial hypertrophy is inappropriate [10]. Increased wall stress is associated with a variety of adverse consequences and thus appears to be the crucial causative prognostic determinant. Increased wall stress leads to opening of stretch-activated ion channels, favors an adverse remodeling, and propagates the vicious circle of ongoing dilatation. Thus, it is suggested to calculate ventricular wall stress in the referenced study [7] and to evaluate its prognostic value. Conflict of interest
⁎ Corresponding author at: University of Marburg, Internal Medicine — Pneumology, German Center for Lung Research, Baldingerstrasse, 35033 Marburg, Germany. E-mail address: [email protected] (P. Alter).
http://dx.doi.org/10.1016/j.ijcard.2014.11.173 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
The authors report no relationships that could be construed as a conflict of interest.
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P. Alter, J.H. Figiel / International Journal of Cardiology 180 (2015) 111–113
Fig. 1. Assessment of late gadolinium enhancement (LGE) in long- and short-axis views using CMR-FLASH sequences (fast low angle shot) in a patient with acute severe myocarditis at time of admission (left column), after 1 (middle column), and 2 months (right column). Initially, typically distributed spots of LGE were observed at the interventricular septum and the lateral free wall. A marked troponin release up to 30 μg/l (normal b0.04 μg/l) was observed. LGE appeared more streaky-like in short axis views. During follow-up, LGE declined consecutively. Streaky-like midwall LGE is typically found in dilated cardiomyopathy. Thus, additional, e.g. edema-sensitive, sequences are required for further diagnostic differentiation.
Fig. 2. Patient with pneumonia and concomitant mild myocarditis. CMR-FLASH sequences (left) showed no LGE. Also, T1-weighted turboFLASH (middle) and edema-sensitive TIRM (turbo inversion recovery magnitude) sequences (right) provided no evidence of myocardial inflammation, although troponin was increased up to 1.5 μg/l (normal b0.04 μg/l). Pneumonia of segment 3 was clearly delineated.
Acknowledgments The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] J.C. Moon, E. Reed, M.N. Sheppard, A.G. Elkington, S.Y. Ho, M. Burke, et al., The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy, J. Am. Coll. Cardiol. 43 (2004) 2260–2264. [2] P. Alter, J.H. Figiel, T.P. Rupp, G.F. Bachmann, B. Maisch, M.B. Rominger, MR, CT, and PET imaging in pericardial disease, Heart Fail. Rev. 18 (2013) 289–306.
[3] P. Alter, J.H. Figiel, M.B. Rominger, Increased ventricular wall stress and late gadolinium enhancement in Takotsubo cardiomyopathy, Int. J. Cardiol. 172 (2014) e184–e186. [4] C.T. Sibley, R.A. Noureldin, N. Gai, M.S. Nacif, S. Liu, E.B. Turkbey, et al., T1 mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy, Radiology 265 (2012) 724–732. [5] S. Dass, J.J. Suttie, S.K. Piechnik, V.M. Ferreira, C.J. Holloway, R. Banerjee, et al., Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy, Circ. Cardiovasc. Imaging 5 (2012) 726–733. [6] V. Hombach, N. Merkle, J. Torzewski, J.M. Kraus, M. Kunze, O. Zimmermann, et al., Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy, Eur. Heart J. 30 (2009) 2011–2018. [7] J. Rodríguez-Capitán, J.M. García-Pinilla, I. Ruiz-Zamora, E. Rueda-Calle, L. MorcilloHidalgo, C. Jurado-Canca, et al., Long-term prognostic value of late gadolinium
P. Alter, J.H. Figiel / International Journal of Cardiology 180 (2015) 111–113 enhancement in a cohort of patients with nonischemic dilated cardiomyopathy, Int. J. Cardiol. 177 (2014) 17–19. [8] P. Alter, H. Rupp, P. Adams, F. Stoll, J.H. Figiel, K.J. Klose, et al., Occurrence of late gadolinium enhancement is associated with increased left ventricular wall stress and mass in patients with non-ischaemic dilated cardiomyopathy, Eur. J. Heart Fail. 13 (2011) 937–944.
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[9] P. Alter, H. Rupp, M.B. Rominger, F. Czerny, A. Vollrath, K.J. Klose, et al., A new method to assess ventricular wall stress in patients with heart failure and its relation to heart rate variability, Int. J. Cardiol. 139 (2010) 301–303. [10] P. Alter, H. Rupp, F. Stoll, P. Adams, J.H. Figiel, K.J. Klose, et al., Increased end diastolic wall stress precedes left ventricular hypertrophy in dilative heart failure—use of the volume-based wall stress index, Int. J. Cardiol. 157 (2012) 233–238.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Prognostic value of late gadolinium enhancement in cardiomyopathy: Causative risk factor or surrogate marker? Peter Alter a,⁎, Jens H. Figiel b a b
University of Marburg, Internal Medicine, Germany University of Marburg, Radiology, Germany
a r t i c l e
i n f o
Article history: Received 30 October 2014 Accepted 23 November 2014 Available online 25 November 2014 Keywords: Late gadolinium enhancement Cardiac magnetic resonance Risk factor Prognosis Dilated cardiomyopathy Heart failure
Assessment of late gadolinium enhancement (LGE) is an integral part of CMR examinations for evaluating myocardial morphology. Occurrence of LGE relies on a prolonged myocardial contrast agent deposition that is used for image acquisition. LGE is a robust diagnostic criterion to delineate postinfarct scar in coronary artery disease. In contrast, causes and consequences of LGE are much less characterized in cardiomyopathies. Although fibrosis was related to LGE in hypertrophic cardiomyopathy [1], this association cannot be generalized. Every alteration (increase) of the interstitial space of arbitrary cause appears to bear a potential source of LGE. For further interpretation, type, pattern, intensity, localization, and duration of LGE need to be taken into account. Separately distributed midwall or transmural spots are typically observed in myocarditis, although a streaky-like midwall pattern, as usually known from chronic dilated cardiomyopathy, can also occur (Fig. 1). Besides this limited diagnostic specificity, also the sensitivity of the method is limited and appears to depend on the severity of disease, i.e. the extent of myocytolysis, necrosis, and edema [2]. The absence of CMR criteria does not exclude myocarditis (Fig. 2). In healed myocarditis and other reversible myocardial injuries, LGE is of transient nature. For instance, LGE, facultatively occurring in the acute stage of Takotsubo syndrome,
disappears in parallel to the decline of ventricular ballooning [3]. Taking the longer half-life of collagen degradation and the observed short-term reversibility of LGE into account, it can be deduced that LGE cannot equal fibrosis per se. Studies using methods of T1 mapping showed an inverse correlation of postcontrast T1 times and myocardial fibrosis as defined by histology [4]. T1 times were shorter in cardiomyopathy with than without LGE, and longest in controls. Increased noncontrast T1 times were correlated with circumferential strain and also observed in myocardial segments unaffected by LGE [5]. Quantification of T1 times appears to be superior to LGE for detecting fibrosis. Other factors involved in the appearance of LGE should be considered. Increased myocardial fibrosis is known to be associated with unfavorable prognostic consequences, e.g. an increased arrhythmia risk, myocardial ischemia and further adverse remodeling. In parallel, several studies were suggestive of adverse prognostic influences of LGE. It was shown that LGE is associated with a worse outcome in dilated cardiomyopathy, but LGE was not an independent predictor by multivariate analysis [6]. In the thorough study by Rodríguez-Capitán et al., the presence of LGE was not associated with an adverse outcome in patients with dilated cardiomyopathy [7], which also argues against a one-toone relation of LGE and fibrosis. The question arises, whether LGE is indeed a causative risk factor or a surrogate marker? It was previously shown, that LGE is associated with increased left ventricular wall stress in dilated cardiomyopathy [8]. It is supposed that increased wall stress leads to a higher interstitial contrast agent deposition or an impaired redistribution into the vasculature, which causes appearance of LGE. Wall stress is predominantly determined by ventricular volumes, myocardial mass and the transmural pressure gradient [9]. Ventricular dilatation leads to an increase of wall stress when myocardial hypertrophy is inappropriate [10]. Increased wall stress is associated with a variety of adverse consequences and thus appears to be the crucial causative prognostic determinant. Increased wall stress leads to opening of stretch-activated ion channels, favors an adverse remodeling, and propagates the vicious circle of ongoing dilatation. Thus, it is suggested to calculate ventricular wall stress in the referenced study [7] and to evaluate its prognostic value. Conflict of interest
⁎ Corresponding author at: University of Marburg, Internal Medicine — Pneumology, German Center for Lung Research, Baldingerstrasse, 35033 Marburg, Germany. E-mail address: [email protected] (P. Alter).
http://dx.doi.org/10.1016/j.ijcard.2014.11.173 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
The authors report no relationships that could be construed as a conflict of interest.
112
P. Alter, J.H. Figiel / International Journal of Cardiology 180 (2015) 111–113
Fig. 1. Assessment of late gadolinium enhancement (LGE) in long- and short-axis views using CMR-FLASH sequences (fast low angle shot) in a patient with acute severe myocarditis at time of admission (left column), after 1 (middle column), and 2 months (right column). Initially, typically distributed spots of LGE were observed at the interventricular septum and the lateral free wall. A marked troponin release up to 30 μg/l (normal b0.04 μg/l) was observed. LGE appeared more streaky-like in short axis views. During follow-up, LGE declined consecutively. Streaky-like midwall LGE is typically found in dilated cardiomyopathy. Thus, additional, e.g. edema-sensitive, sequences are required for further diagnostic differentiation.
Fig. 2. Patient with pneumonia and concomitant mild myocarditis. CMR-FLASH sequences (left) showed no LGE. Also, T1-weighted turboFLASH (middle) and edema-sensitive TIRM (turbo inversion recovery magnitude) sequences (right) provided no evidence of myocardial inflammation, although troponin was increased up to 1.5 μg/l (normal b0.04 μg/l). Pneumonia of segment 3 was clearly delineated.
Acknowledgments The authors of this manuscript certify that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] J.C. Moon, E. Reed, M.N. Sheppard, A.G. Elkington, S.Y. Ho, M. Burke, et al., The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy, J. Am. Coll. Cardiol. 43 (2004) 2260–2264. [2] P. Alter, J.H. Figiel, T.P. Rupp, G.F. Bachmann, B. Maisch, M.B. Rominger, MR, CT, and PET imaging in pericardial disease, Heart Fail. Rev. 18 (2013) 289–306.
[3] P. Alter, J.H. Figiel, M.B. Rominger, Increased ventricular wall stress and late gadolinium enhancement in Takotsubo cardiomyopathy, Int. J. Cardiol. 172 (2014) e184–e186. [4] C.T. Sibley, R.A. Noureldin, N. Gai, M.S. Nacif, S. Liu, E.B. Turkbey, et al., T1 mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy, Radiology 265 (2012) 724–732. [5] S. Dass, J.J. Suttie, S.K. Piechnik, V.M. Ferreira, C.J. Holloway, R. Banerjee, et al., Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy, Circ. Cardiovasc. Imaging 5 (2012) 726–733. [6] V. Hombach, N. Merkle, J. Torzewski, J.M. Kraus, M. Kunze, O. Zimmermann, et al., Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy, Eur. Heart J. 30 (2009) 2011–2018. [7] J. Rodríguez-Capitán, J.M. García-Pinilla, I. Ruiz-Zamora, E. Rueda-Calle, L. MorcilloHidalgo, C. Jurado-Canca, et al., Long-term prognostic value of late gadolinium
P. Alter, J.H. Figiel / International Journal of Cardiology 180 (2015) 111–113 enhancement in a cohort of patients with nonischemic dilated cardiomyopathy, Int. J. Cardiol. 177 (2014) 17–19. [8] P. Alter, H. Rupp, P. Adams, F. Stoll, J.H. Figiel, K.J. Klose, et al., Occurrence of late gadolinium enhancement is associated with increased left ventricular wall stress and mass in patients with non-ischaemic dilated cardiomyopathy, Eur. J. Heart Fail. 13 (2011) 937–944.
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[9] P. Alter, H. Rupp, M.B. Rominger, F. Czerny, A. Vollrath, K.J. Klose, et al., A new method to assess ventricular wall stress in patients with heart failure and its relation to heart rate variability, Int. J. Cardiol. 139 (2010) 301–303. [10] P. Alter, H. Rupp, F. Stoll, P. Adams, J.H. Figiel, K.J. Klose, et al., Increased end diastolic wall stress precedes left ventricular hypertrophy in dilative heart failure—use of the volume-based wall stress index, Int. J. Cardiol. 157 (2012) 233–238.
