JOURNAL OF MAGNETIC RESONANCE IMAGING 39:1153–1160 (2014)
Original Research
Assessment of Nonischemic Fibrosis in Hypertrophic Cardiomyopathy: Comparison of Gadopentetate Dimeglumine and Gadobenate Dimeglumine for Enhanced Cardiovascular Magnetic Resonance Imaging Andre Rudolph, MD,1,2* Florian von Knobelsdorff-Brenkenhoff, MD,1,2 Ralf Wassmuth, MD,1,2 Marcel Prothmann, MD,1,2 Wolfgang Utz, MD,1,2 and Jeanette Schulz-Menger, MD1,2 Purpose: To compare whether the higher relaxivity contrast agent gadobenate is superior for the identification of nonischemic late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) compared to standard relaxivity agents such as gadopentetate.
criteria and definitions) was higher with gadobenate dimeglumine (12.7 6 8.5 g vs. 9.4 6 5.6 g, P ¼ 0.005). There was no difference in intra- and interobserver variability between gadopentetate dimeglumine and gadobenate dimeglumine.
Materials and Methods: Fifteen patients with HCM and positive LGE based on routine cardiac magnetic resonance (CMR) with 0.2 mmol/kg gadopentetate were enrolled. Each patient thereafter underwent a second enhanced CMR exam with 0.2 mmol/kg gadobenate using the same CMR protocol. LGE was assessed in a short axis stack acquired after contrast administration using an inversion recovery gradient echo sequence. Two independent blinded readers quantified LGE by manual planimetry. The signal intensities of injured myocardium, remote myocardium, left ventricular cavity, and air were measured in identical locations using anatomical landmarks and dedicated software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated.
Conclusion: CMR with the high relaxivity contrast agent gadobenate dimeglumine reveals significantly more tissue with LGE in patients with HCM. Key Words: hypertrophic cardiomyopathy; late gadolinium enhancement; gadobenate dimeglumine J. Magn. Reson. Imaging 2014;39:1153–1160. C 2013 Wiley Periodicals, Inc. V
Results: No adverse events related to contrast administration occurred. Gadobenate dimeglumine showed a higher SNR of injured myocardium (45.4 6 24.0 vs. 31.1 6 16.6, P ¼ 0.002) and a higher CNR between remote and injured myocardium (37.6 6 25.0 vs. 26.5 6 17.6, P ¼ 0.006) compared to gadopentetate dimeglumine. The amount of LGE (based on the same postprocessing
1 Working Group on Cardiovascular Magnetic Resonance, Experimental Clinical Research Center, a joint cooperation between the Charit e Medical Faculty and the Max-Delbr€ uck Center for Molecular Medicine, Berlin, Germany. 2 HELIOS Klinikum Berlin-Buch, Department of Cardiology and Nephrology, Berlin, Germany. Contract grant sponsor: Bracco and by institutional grants held by Jeanette Schulz-Menger. *Address reprint requests to: A.R., Working Group on Cardiovascular Magnetic Resonance, HELIOS Klinikum Berlin-Buch, Dept. of Cardiology and Nephrology, Schwanebecker Chaussee 50, 13125, Berlin, Germany. E-mail: [email protected] Received July 6, 2012; Accepted May 16, 2013. DOI 10.1002/jmri.24264 View this article online at wileyonlinelibrary.com. C 2013 Wiley Periodicals, Inc. V
HYPERTROPHIC CARDIOMYOPATHY (HCM) is the most common genetic cardiac disease, with an estimated prevalence of 0.2%, and is the most frequent cause of sudden cardiac death (SCD) in young people (1–3). Clinical challenges associated with HCM include the identification of patients at risk for SCD or heart failure and the recognition of early disease. Histopathological studies have shown an increase of myocardial fibrosis in HCM (4), and myocardial fibrosis itself is associated with increased risk of SCD and congestive heart failure (5,6). Cardiac magnetic resonance (CMR) is an emerging tool for diagnosis and risk stratification in HCM. CMR is the reference standard technique for noninvasive assessment of left ventricular (LV) function as well as LV mass, which has been shown to be a predictor of adverse outcomes in HCM (7). Late gadolinium enhancement (LGE) provides additional information on focal increases of myocardial fibrosis in HCM (8–11). Numerous studies have revealed a high prevalence of LGE predominantly in regions of hypertrophy with a diffuse and nonsubendocardial pattern (12,13). The extent of LGE seems to be associated with the severity
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Rudolph et al.
Figure 1. Quantification of LGE; left: LGE image in short axis orientation, middle: manual tracing of LGE; right: verifying the contours by using the threshold meanþ2SD (blue ROI ¼ remote myocardium, red enlightened ¼ myocardium above the threshold).
of LV remodeling and with ventricular arrhythmias in HCM (14,15). Noninvasive quantification of fibrosis may offer the possibility for risk stratification. However, due to the diffuse and blurred distribution of fibrosis these lesions are often difficult to differentiate from healthy myocardium. Recent studies have demonstrated superiority for the higher relaxivity contrast agent gadobenate dimeglumine (Gd-BOPTA; MultiHance; Bracco Imaging, Milan, Italy) compared to the standard relaxivity agent gadopentetate dimeglumine (Gd-DTPA; Magnevist; Bayer Healthcare, Berlin, Germany) for the delineation of infarcted from viable myocardium in coronary artery disease (CAD) (16,17). However, particularly in small scars, the low contrast between bright subendocardial scars and relatively bright blood can be challenging. On the other hand, the localization of LGE in HCM is mostly nonsubendocardial (13). Therefore, we hypothesized that Gd-BOPTA may have advantages over Gd-DTPA for depiction of nonischemic fibrosis.
PATIENTS AND METHODS Patients Ethical approval was obtained from the local Research Ethics Committee. Between August 2007 and March 2010, patients with clinically established HCM according to current guidelines (18) including echocardiography and positive LGE during routine CMR with 0.2 mmol/kg BW Gd-DTPA were screened and invited to undertake a second study-related CMR scan for research purposes. After signing informed consent each patient was scheduled for a second, identical CMR examination using the same protocol and image parameters but with 0.2 mmol/kg GdBOPTA as contrast agent rather than 0.2 mmol/kg BW Gd-DTPA. Patients with severe arrhythmia, renal failure (GFR
Original Research
Assessment of Nonischemic Fibrosis in Hypertrophic Cardiomyopathy: Comparison of Gadopentetate Dimeglumine and Gadobenate Dimeglumine for Enhanced Cardiovascular Magnetic Resonance Imaging Andre Rudolph, MD,1,2* Florian von Knobelsdorff-Brenkenhoff, MD,1,2 Ralf Wassmuth, MD,1,2 Marcel Prothmann, MD,1,2 Wolfgang Utz, MD,1,2 and Jeanette Schulz-Menger, MD1,2 Purpose: To compare whether the higher relaxivity contrast agent gadobenate is superior for the identification of nonischemic late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) compared to standard relaxivity agents such as gadopentetate.
criteria and definitions) was higher with gadobenate dimeglumine (12.7 6 8.5 g vs. 9.4 6 5.6 g, P ¼ 0.005). There was no difference in intra- and interobserver variability between gadopentetate dimeglumine and gadobenate dimeglumine.
Materials and Methods: Fifteen patients with HCM and positive LGE based on routine cardiac magnetic resonance (CMR) with 0.2 mmol/kg gadopentetate were enrolled. Each patient thereafter underwent a second enhanced CMR exam with 0.2 mmol/kg gadobenate using the same CMR protocol. LGE was assessed in a short axis stack acquired after contrast administration using an inversion recovery gradient echo sequence. Two independent blinded readers quantified LGE by manual planimetry. The signal intensities of injured myocardium, remote myocardium, left ventricular cavity, and air were measured in identical locations using anatomical landmarks and dedicated software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated.
Conclusion: CMR with the high relaxivity contrast agent gadobenate dimeglumine reveals significantly more tissue with LGE in patients with HCM. Key Words: hypertrophic cardiomyopathy; late gadolinium enhancement; gadobenate dimeglumine J. Magn. Reson. Imaging 2014;39:1153–1160. C 2013 Wiley Periodicals, Inc. V
Results: No adverse events related to contrast administration occurred. Gadobenate dimeglumine showed a higher SNR of injured myocardium (45.4 6 24.0 vs. 31.1 6 16.6, P ¼ 0.002) and a higher CNR between remote and injured myocardium (37.6 6 25.0 vs. 26.5 6 17.6, P ¼ 0.006) compared to gadopentetate dimeglumine. The amount of LGE (based on the same postprocessing
1 Working Group on Cardiovascular Magnetic Resonance, Experimental Clinical Research Center, a joint cooperation between the Charit e Medical Faculty and the Max-Delbr€ uck Center for Molecular Medicine, Berlin, Germany. 2 HELIOS Klinikum Berlin-Buch, Department of Cardiology and Nephrology, Berlin, Germany. Contract grant sponsor: Bracco and by institutional grants held by Jeanette Schulz-Menger. *Address reprint requests to: A.R., Working Group on Cardiovascular Magnetic Resonance, HELIOS Klinikum Berlin-Buch, Dept. of Cardiology and Nephrology, Schwanebecker Chaussee 50, 13125, Berlin, Germany. E-mail: [email protected] Received July 6, 2012; Accepted May 16, 2013. DOI 10.1002/jmri.24264 View this article online at wileyonlinelibrary.com. C 2013 Wiley Periodicals, Inc. V
HYPERTROPHIC CARDIOMYOPATHY (HCM) is the most common genetic cardiac disease, with an estimated prevalence of 0.2%, and is the most frequent cause of sudden cardiac death (SCD) in young people (1–3). Clinical challenges associated with HCM include the identification of patients at risk for SCD or heart failure and the recognition of early disease. Histopathological studies have shown an increase of myocardial fibrosis in HCM (4), and myocardial fibrosis itself is associated with increased risk of SCD and congestive heart failure (5,6). Cardiac magnetic resonance (CMR) is an emerging tool for diagnosis and risk stratification in HCM. CMR is the reference standard technique for noninvasive assessment of left ventricular (LV) function as well as LV mass, which has been shown to be a predictor of adverse outcomes in HCM (7). Late gadolinium enhancement (LGE) provides additional information on focal increases of myocardial fibrosis in HCM (8–11). Numerous studies have revealed a high prevalence of LGE predominantly in regions of hypertrophy with a diffuse and nonsubendocardial pattern (12,13). The extent of LGE seems to be associated with the severity
1153
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Rudolph et al.
Figure 1. Quantification of LGE; left: LGE image in short axis orientation, middle: manual tracing of LGE; right: verifying the contours by using the threshold meanþ2SD (blue ROI ¼ remote myocardium, red enlightened ¼ myocardium above the threshold).
of LV remodeling and with ventricular arrhythmias in HCM (14,15). Noninvasive quantification of fibrosis may offer the possibility for risk stratification. However, due to the diffuse and blurred distribution of fibrosis these lesions are often difficult to differentiate from healthy myocardium. Recent studies have demonstrated superiority for the higher relaxivity contrast agent gadobenate dimeglumine (Gd-BOPTA; MultiHance; Bracco Imaging, Milan, Italy) compared to the standard relaxivity agent gadopentetate dimeglumine (Gd-DTPA; Magnevist; Bayer Healthcare, Berlin, Germany) for the delineation of infarcted from viable myocardium in coronary artery disease (CAD) (16,17). However, particularly in small scars, the low contrast between bright subendocardial scars and relatively bright blood can be challenging. On the other hand, the localization of LGE in HCM is mostly nonsubendocardial (13). Therefore, we hypothesized that Gd-BOPTA may have advantages over Gd-DTPA for depiction of nonischemic fibrosis.
PATIENTS AND METHODS Patients Ethical approval was obtained from the local Research Ethics Committee. Between August 2007 and March 2010, patients with clinically established HCM according to current guidelines (18) including echocardiography and positive LGE during routine CMR with 0.2 mmol/kg BW Gd-DTPA were screened and invited to undertake a second study-related CMR scan for research purposes. After signing informed consent each patient was scheduled for a second, identical CMR examination using the same protocol and image parameters but with 0.2 mmol/kg GdBOPTA as contrast agent rather than 0.2 mmol/kg BW Gd-DTPA. Patients with severe arrhythmia, renal failure (GFR
