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Available online at www.sciencedirect.com

www.elsevier.com/locate/tcm

Editorial Commentary

Cardiac magnetic resonance imaging and electrophysiology “the beauty is in the eye of the beholder” Jorge Romero, MDa,d, Andrea Natale, MDb,c,f,g,h,i, and Luigi Di Biase, MD, PhDb,c,d,e,n a

Ronald Reagan UCLA Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, TX c Department of Biomedical Engineering, University of Texas, Austin, TX d Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY e Department of Cardiology, University of Foggia, Foggia, Italy f Division of Cardiology, Stanford University, Palo Alto, CA g Case Western Reserve University, Cleveland, OH h Scripps Clinic, San Diego, CA i Dell Medical School, Austin, TX b

Different non-invasive imaging modalities have played a substantial role in the armamentarium of the electrophysiologist to treat patients with different arrhythmias. Cardiac magnetic resonance imaging (CMRI) has gained popularity in the last 2 decades due to technological innovations, such as electrocardiographic gating and respiratory motion suppression methods that facilitate high-quality cross-sectional images of the heart, providing an exceptional spatial resolution predominantly in the left ventricle [1]. Delayed gadolinium enhancement DE-CMRI has been proven to be the gold standard in the identification of myocardyal scar [2,3]. Furthermore, CMRI is an accurate imaging modality for the assessment of myocardial viability, differentiating between viable (hibernating) and non-viable myocardium as well as transmural from subendocardial infarcts [4]. Despite the fact

that some arrhythmic substrates such as arrhythmogenic right ventricular dysplasia (ARVD), Brugada syndrome, and Chagas cardiomyopathy have already been established to require epicardial mapping and ablation and several electrocardiographic criteria for epicardial origin of VT have been identified [5], CMRI might help in the pre-procedural planning in the vast majority of patients with ischemic and nonischemic cardiomyopathy to determine the presence of mid-myocardial or epicardial scars [6,7]. CMRI may also reproduce detailed characterization of scar by differentiating the core and the border zones [8]. Nonetheless, as the authors covered in detail in this issue of Trends in cardiovascular Medicine [9], the data published in the medical literature have shown controversial results in terms of VT substrates when the two main scar areas have been compared (i.e., core vs.

Disclosures: Dr. Di Biase is a consultant for Biosense Webster, Boston Scientific and St. Jude Medical. Dr. Di Biase received speaker honoraria/travel from Medtronic, Atricure, EPiEP and Biotronik. Dr. Natale received speaker honorariums from Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik and Medtronic, Dr. Natale is a consultant for Biosense Webster St. Jude Medical and Janssen. Dr. Romero has no disclosures. The authors have indicated there are no conflicts of interest. n Corresponding author at: Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, NY 10467. E-mail address: [email protected] (L. Di Biase). http://dx.doi.org/10.1016/j.tcm.2015.04.006 1050-1738/& 2015 Elsevier Inc. All rights reserved.

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border zone). We believe that it is to be expected when completely different methodologies have been implemented in most studies. As is well known, several approaches and strategies for mapping and ablation have been proposed and tested for VT with no unique standardized protocol to date. It becomes even more cumbersome to analyze when presence of microvascular obstruction and intramyocardial hemorrhage with DE-MRI are brought into the equation [10]. Yan et al. [11] published a study that hypothesized that the extent of the peri-infarct zone quantified by CMRI was an independent predictor of post-MI mortality due to arrhythmias. They measured the total infarct size and divided it into the core and peri-infarct regions based on signalintensity thresholds. After 2.4 years of follow-up, 29 patients died (20%). Patients who had higher percentages of periinfarct area had a higher mortality compared to those who had low peri-infarct areas (28% vs. 13%, log-rank P o 0.01). They concluded that the extent of the peri-infarct zone characterized by CMRI provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction as non-invasive predictors for post-MI mortality [11]. Ongoing studies are aiming to correlate the transmural extent and intramural types of scar (i.e., endocardial, midwall, epicardial, patchy, dense, and transmural) as well as the border zone/core ratios with short- and longterm clinical outcomes (e.g., mortality and VT recurrences) in patients undergoing VT ablation. CMRI might also detect and measure myocardial scar in the right ventricle (RV) and help in the diagnosis of rare cardiomyopathies such as ARVD or sarcoidosis [12]. CMRI is widely used for the diagnosis of ARVD. CMRI can identify global or regional ventricular dilation, dysfunction, intramyocardial fat, aneurysmatic dilation, and fibrosis. Yet, identification of DE by CMRI in the RV is not a part of the diagnostic criteria of ARVD as it is seen in the latest modified task force criteria for ARVD [13]. Initially in 2005, DE CMRI was utilized particularly for the detection of fibrotic tissue but showed a low sensitivity of 66% with a specificity of 100% [12]. More recently, we demonstrated that delayed enhancement is significantly associated with the distribution of low voltage areas detected by electroanatomic mapping in the free and inferoposterior walls and outflow tract region [14]. Nonetheless a study comparing voltage mapping vs. CRMI to identify myocardial scar revealed that voltage mapping is still more sensitive in diagnosing this entity with significant less false negatives [15]. We agree with the authors of the present review article that the current imaging resolution of CMRI to delineate arrhythmic substrate in the RV and left atrium (LA) is somewhat limited [9]. Similarly, although promising data from the landmark study by Marrouche et al. [16], in which scar burden in the LA is a strong independent predictor of atrial fibrillation recurrence, have already been corroborated by other groups, and a few more studies have demonstrated the role of pre-procedural DE-CMR successfully guiding repeated pulmonary vein isolation procedures by accurately identifying and localizing gaps, which in turn may reduce procedural duration, fluoroscopy, and radiofrequency application times, the software used in those studies to quantity and localize LA scar is not widely available in clinical practice. Furthermore, a multicenter study concluded that DE CMRI of atrial scar is not yet sufficiently accurate to reliably identify ablation lesions or to

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determine lesion distribution with current technology [17]. It is tempting to speculate that refinements in real-time CMRIguided radiofrequency ablation will truly have a major impact on ablation of atrial fibrillation for visualization and further characterization of lesion formation in order to increase success rate and avoid esophageal injuries [18,19]. No more than five centers nationwide have built electrophysiology laboratories with integrated CMRI, due primarily to massive expenses. Once CMRI technology improves, and delayed enhancement can be measured accurately in the LA and RV, this would definitely have a significant impact on clinical practice since it would avoid unnecessary and ineffective highrisk invasive ablative procedures. On the other hand, the authors presented several articles demonstrating that integration of CMRI scar characterization into navigation systems during VT ablation can be precisely performed, which saves significant procedural time practically avoiding voltage mapping. Albeit this feature appears provocative, we currently can perform endocardial and epicardial voltage mapping using multi-electrode catheters (i.e., DuoDecapolar catheter with short electrode spacing 2–2–2 mm) in just a few minutes with the advantage that delayed low amplitude fractionated electrograms can also be identified to guide ablation. Two shortcomings of CMRI are worth mentioning. First of all, CMRI might have potential problems in patients with some metallic implants. However, devices such as intravascular stents, most prosthetic cardiac valves, and prosthetic joints placed within the last two decades are considered “MRI safe.” Conversely, pacemakers and implantable-cardioverter defibrillators (ICD) are still considered a strong relative contraindication to MRI examination due to the risk of arrhythmia induction, device movement and specially “lead heating” [20]. MRI compatible pacemakers have ameliorated this problem to some extent, yet a large percentage of our patients with cardiac arrhythmias, particularly experiencing VT, unfortunately have already undergone ICD implantation either for primary or secondary prevention of sudden cardiac death. Even though a few centers in the United States safely perform CMRI on a daily basis on these patients, this is not the case elsewhere given the fact this practice is not approved by the Food and Drug Administration. Moreover, ICD artifact dramatically obscures image integrity and the clinical utility of CMRI. A novel wideband LGE MRI technique was recently developed to improve the ability to visualize myocardium for clinical interpretation, which has correlated well with electroanatomic mapping findings during VT ablation. Secondly, nephrogenic systemic fibrosis is a devastating (albeit extremely rare) potential complication in patients exposed to gadolinium-based contrast agents. This complication occurs almost exclusively in patients with moderate to severe renal disease, particularly those on dialysis with incidences in patients on either hemodialysis or peritoneal dialysis ranging from 2.5% to 5% [21,22]. Finally, despite the major advancements in this imaging modality, CMRI is timeconsuming, expensive, and requires experienced personnel for adequate image acquisition and analysis. Likewise, it still has inadequate spatial resolution in the LA and RV that limits its routine use for most arrhythmias in this field. It is debatable at this moment whether obtaining CMRI in all

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patients being considered for VT or atrial fibrillation ablation is likely to be worthwhile. [12]

re fe r en ces [13] [1]

Hundley WG, et al. Comparison of quantitation of left ventricular volume, ejection fraction, and cardiac output in patients with atrial fibrillation by cine magnetic resonance imaging versus invasive measurements. Am J Cardiol 1996;78:1119–23. [2] Lima JA, et al. Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms. Circulation 1995;92:1117–25. [3] Kim RJ, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992–2002. [4] Kim RJ, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343:1445–53. [5] Berruezo A, et al. Electrocardiographic recognition of the epicardial origin of ventricular tachycardias. Circulation 2004;109:1842–7. [6] Van Asperen PP, Kemp AS, Mellis CM. A prospective study of the clinical manifestations of atopic disease in infancy. Acta Paediatr 1984;73:80–5. [7] Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J 2005;26:1461–74. [8] Saeed M, et al. Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media. Circulation 2001;103:871–6. [9] Esra Gucuk Ipek SN. Cardiac magnetic resonance for prediction of arrhythmogenic areas. Trends Cardiovasc Med 2015;25:635–42. [10] Hamirani YS, Wong A, Kramer CM, Salerno M. Effect of microvascular obstruction and intramyocardial hemorrhage by CMR on LV remodeling and outcomes after myocardial infarction: a systematic review and meta-analysis. JACC Cardiovasc Imaging 2014;7:940–52. [11] Yan AT, et al. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a

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powerful predictor of post-myocardial infarction mortality. Circulation 2006;114:32–9. Tandri H, et al. Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging. J Am Coll Cardiol 2005;45:98–103. Marcus FI, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 2010;121:1533–41. Santangeli P, et al. Noninvasive diagnosis of electroanatomic abnormalities in arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2010;3:632–8. Marra MP, et al. Imaging study of ventricular scar in arrhythmogenic right ventricular cardiomyopathy: comparison of 3D standard electroanatomical voltage mapping and contrast-enhanced cardiac magnetic resonance. Circ Arrhythm Electrophysiol 2012;5:91–100. Marrouche NF, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. J Am Med Assoc 2014;311:498–506. Hunter RJ, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24:396–403. Vergara GR, et al. Real-time magnetic resonance imagingguided radiofrequency atrial ablation and visualization of lesion formation at 3 Tesla. Heart Rhythm 2011;8:295–303. Bisbal F, et al. CMR-guided approach to localize and ablate gaps in repeat AF ablation procedure. JACC Cardiovasc Imaging 2014;7:653–63. Levine GN, et al. Safety of magnetic resonance imaging in patients with cardiovascular devices: an American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Council on Cardiovascular Radiology and Intervention: endorsed by the American College of Cardiology Foundation, the North American Society for Cardiac Imaging, and the Society for Cardiovascular Magnetic Resonance. Circulation 2007;116:2878–91. Deo A, Fogel M, Cowper SE. Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol 2007;2:264–7. Shabana WM, et al. Nephrogenic systemic fibrosis: a report of 29 cases. Am J Roentgenol 2008;190:736–41.

Cardiac magnetic resonance imaging and electrophysiology "the beauty is in the eye of the beholder".

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