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J Cardiovasc Magn Reson
J Cardiovasc Magn Reson
Journal of Cardiovascular Magnetic Resonance
1097-6647
1532-429X
Elsevier

S1097-6647(24)01102-5
10.1016/j.jocmr.2024.101075
101075
Editorial
Late gadolinium enhancement and the diagnosis of arrhythmogenic right ventricular cardiomyopathy
Bluemke David A. dbluemke@wisc.edu
1
Department of Radiology, The University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792, USA
1 https://orcid.org/0000-0002-8323-8086

31 7 2024
2024
31 7 2024
26 2 101075© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Abbreviations

CMR cardiovascular magnetic resonance

ARVC arrhythmogenic right ventricular cardiomyopathy

ARVD arrhythmogenic right ventricular dysplasia

ARVD/C arrhythmogenic right ventricular dysplasia/cardiomyopathy

ALVC arrhythmogenic left ventricular cardiomyopathy

AC/ACM arrhythmogenic cardiomyopathy

DS desmoplakin

HRS Heart Rhythm Society

LGE late gadolinium enhancement
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pmcThe cardiovascular magnetic resonance (CMR) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is notoriously difficult. I have been challenged with this diagnosis in my clinical practice and research for the past 30 years. Over that time, knowledge has grown regarding the genetic basis of ARVC, while the CMR description of ARVC continues to be complex. Even the name of the disease has become difficult to understand, with variations of alphabet soup acronyms ranging from AC, ACM, ARVC, ARVD, ARVD/C, and ALVC having been put forth (see Table 1 for abbreviations). Are these diseases the same or different? If so, why and when?Table 1 Abbreviations used to describe arrhythmogenic right ventricular cardiomyopathy (ARVC) and its variants.

Table 1Abbreviation	Definition	Explanation/use in the literature	
ARVD	Arrhythmogenic right ventricular dysplasia	No longer used; ARVC is not considered a dysplastic condition.	
ARVD/C	Arrhythmogenic right ventricular dysplasia/ cardiomyopathy	This intermediate term was used for the Task Force Criteria [2] before stopping the use of the term “dysplasia.” No longer used.	
ARVC	Arrhythmogenic right ventricular cardiomyopathy	Used when right or biventricular predominant disease is present.	
ALVC	Arrhythmogenic left ventricular cardiomyopathy	Used when left ventricular predominant disease is present.	
AC	Arrhythmogenic cardiomyopathy	Single umbrella term used by specialists, to include right, biventricular, and left ventricular disease expression.	
ACM	Arrhythmogenic cardiomyopathy	Used by the Heart Rhythm Society to describe various conditions (not diseases) that present with both ventricular dysfunction and arrhythmia [7]. Examples include ARVC, sarcoidosis, amyloidosis, and other nonischemic cardiomyopathies.	

Let me start with a description of ARVC. ARVC presents as electrical instability of the heart and consequently, risk for sudden cardiac death typically in relatively young individuals. The most frequent cause is related to genetic variants that affect the myocardial desmosome. The desmosome is composed of multiple proteins; thus, several different genetic abnormalities may cause ARVC. Desmosomes connect adjacent myocardial cells to maintain structural connections between myocytes. Gap junctions and ion channels are adjacent to the desmosomes; lack of structural connections (by the desmosome) is thought to result in abnormal electrical communications (by the gap junctions) between myocardial cells [1]. The most common imaging features of ARVC are structural and functional abnormalities of the right ventricle or both ventricles [2].

The prior name for arrhythmogenic right ventricular cardiomyopathy was “ARVD,” now considered to be outdated. The “D” in the acronym stood for dysplasia (abnormal growth or development of cells) which is not a component of the disease. Today, ARVC is considered a nonischemic cardiomyopathy with genetic etiology [3].

The last update on the criteria for diagnosis of ARVC was in 2010 [2], resulting in the so-called Task Force criteria for ARVD/C. The 2010 Task Force criteria were largely based on a National Institutes of Health–sponsored prospective study involving research participants in the United States and Canada [4]. In that study, the most common desmosomal genetic abnormality concerned mutations of plakophilin-2 gene, usually resulting in right ventricular or biventricular disease. However, in 2008, Sen-Chowdhry upended our thinking by describing eight patients with left dominant disease [5], most with genetic alterations in the gene for desmoplakin (DS), also a component of the desmosome. Thus, we arrived at a confusing point for the field: left predominant ARVC.

In other words, once again we had the wrong name for this arrhythmogenic genetic disease—not a dysplasia, and also not exclusively a right-sided disease. And, not exclusively a disease of proteins that constitute the desmosome [6].

Time for another name change, at least for specialists: arrhythmogenic cardiomyopathy, sometimes abbreviated as AC. To specialists in the field, AC encompasses the spectrum of genetic diseases characterized by electrical instability of the heart, cardiomyocyte loss, and fibrofatty replacement of the myocardium. In this article for the sake of clarity, I will instead use the more familiar term ARVC, hoping to provide a bit more specific message to the reader.

There remains one additional point that may be confusing for CMR physicians; in 2019, the Heart Rhythm Society (HRS) also decided to use the term “arrhythmogenic cardiomyopathy” (abbreviated as ACM) to define a broad set of myocardial conditions (rather than a single disease). To the HRS, arrhythmogenic cardiomyopathy includes any disease with a) ventricular dysfunction and b) arrhythmia as part of the clinical presentation (except for arrhythmia caused by ischemic, hypertensive, or valvular heart disease) [7]. According to the HRS, these conditions of arrhythmogenic cardiomyopathy are found in at least 10 different diseases, such as sarcoidosis, amyloidosis, myocarditis, Chagas disease, and ARVC.

In my own CMR practice, 90% of referrals for cardiomyopathy evaluation fall within the HRS’s broad class of conditions described as “ACM.” The rationale for CMR evaluation of ACM is that CMR can frequently differentiate the various diseases (e.g., ARVC vs amyloidosis) that fall under the general rubric of ACM.

The recent publication by Rekker et al. [8] seeks to determine the utility of CMR for the differential diagnosis of ARVC. The 2010 Task Force criteria do not include evaluation of late gadolinium enhancement (LGE) as the method was not widely used at that time. Therefore, Rekker et al. specifically focused on patterns of LGE for differential diagnosis of ARVC. The authors selected cases of ARVC (n = 55), dilated cardiomyopathy (n = 25), resolved myocarditis (n = 13), sarcoidosis (n = 20), and amyloidosis (n = 19) from the UNRAVEL database (https://www.unravelrdp.nl/). Selected patients had an identified cardiomyopathy and available CMR images.

Rekker et al. found that right ventricular LGE is no more common in ARVC than in the other four selected cardiomyopathies. In their study, about one-third of the ARVC subjects had LGE. This seems consistent with my own clinical experience. However, when we first described the value of LGE in ARVC in 2005, about two-thirds of our patients had right ventricular LGE [9]. Differences in prevalence rates of LGE are due to small sample sizes and differences in the referral population. However, it is clear that the mere presence of LGE in the right ventricle does not differentiate ARVC from other nonischemic cardiomyopathies.

By considering the number of segments of involvement in both the left and right ventricles, Rekker et al. observed better discrimination of ARVC from other cardiomyopathies. The authors described a set of four complex conditions that more reliability differentiated ARVC from other diseases [8]. In essence, these conditions support the high specificity for the “bite-wing” pattern of LGE in the inferolateral wall of the left ventricle on both CMR [10] and computed tomography [11].

An interesting new proposal to help diagnose ARVC is the so-called Padua criteria [12]. As yet untested, the Padua criteria seek to incorporate the use of LGE CMR along with slightly modified ARVC Task Force criteria [2]. The Padua criteria provide criteria for left predominant arrhythmogenic cardiomyopathy together with traditional ARVC, under the single umbrella of arrhythmogenic cardiomyopathy (AC). The data from Rekker et al. show that consideration of LGE patterns with the Padua criteria still results in diagnostic ambiguity between AC and other cardiomyopathies.

Many dozens of different nonischemic cardiomyopathies [3] have been described. LGE CMR classification as present or absent is clearly insufficient for differentiation. Even if we add the pattern of LGE (base, mid or apex, and transmurality), we cannot hope to provide specific diagnoses for all cardiomyopathies. The most useful approach is likely to include referrals with high pre-test probability for ARVC, including genetic results. At that point, we can deploy the full power of CMR using myocardial mapping and detailed functional analysis of the myocardium.

Importantly, over the last 20 years, we have learned that certain patterns of LGE are helpful for differential diagnosis, and the study by Rekker et al. adds to that knowledge. Remaining efforts to combine hundreds of CMR parameters, genetics, and clinical parameters using artificial intelligence will eventually advance our diagnostic abilities to provide greater reliability and specificity for CMR diagnosis.
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