Number 10-20: Electrophysiologic and CMR features of ARVC
Case from: N. Feranec, W. Miles, J. Petersen, G. Cooper. Institution: CMR and Electrophysiology Services, University of Florida, Gainesville, FL, USA.
Clinical history: A 19 year old caucasian female with documented ventricular tachycardia was referred to electrophysiology service. There was no family history of sudden cardiac death, syncope or ventricular arrhythmias. The ECG 1 was abnormal and demonstrated low voltage, right axis deviation with T wave inversion in V1-V4. The QT interval was normal. There was no suggestion of Brugada's syndrome.
The physical examination was normal. The serum electrolytes and hematologic profile were within normal range. The transthoracic echocardiogram showed biventricular systolic dysfunction and therefore the patient was referred for CMR to further evaluate the possibility of ARVC(D). CMR demonstrated biventricular systolic dysfunction (RVEF 21% & LVEF 41%) (Movie 1). The RV was thin, dilated and hypokinetic. The RV diaphragmatic wall was akinetic and a small right ventricular aneurysm was seen at the junction of the RV lateral wall with the diaphragmatic wall (Movie 2). Left ventricle displayed moderate global hypokinesis. Axial T1 and T2 images without and with fat saturation show no evidence of fatty infiltration of the RV wall (Fig 1, 2, 3 and 4).
Fig 1: T1 without fat sat Fig 2: T1 with fat sat
Fig 3: T2 without fat sat Fig 4: T2 with fat sat
Late Gadolinium Enhancement (LGE) series ( Fig 5 and 6) show that the entire right ventricular wall and the LV apical wall were replaced with fibrous tissue. The patient was brought to the electrophysiology lab where programmed stimulation reproduced her ventricular tachycardia (ECG 2). An intra-cardiac RV voltage map demonstrated severe, diffuse reduction in right ventricular voltage. A normal and our patient's voltage map are presented for comparison (Fig 7). The voltage amplitude is identified by the color bar in the right upper corner - click to enlarge. The orientation is illustrated by the cartoon at the bottom left. An AICD was implanted.
When doing a CMR in a patient with ?ARVC, you need to acquire the relevant images and image planes following SCMR official standardized acquisition guidelines and then establish whether: 1) RV function is normal/abnormal; 2) accurately calculate RV volumes and EF; 3) assess the presence of RV regional wall motion abnormalities, wall thinning or aneurismal formation; 4) assess the presence of RV fatty infiltration; 5) assess the presence of RV myocardial fibrosis; 6) assess whether there is LV involvement.
Unfortunately, this is very often not an easy task and there are intrinsic difficulties due to:1) extreme variability of RV anatomy even in the normal population; 2) through-plane motion can mimic regional wall motion abnormalities; 4) the insertion of the moderator band into the RV free wall often creates a localized "regional wall motion abnormality" that shouldn't often be considered pathological; 5) blood pooling and artefacts in LGE imaging can mimic the presence of genuine myocardial fibrosis; 6) the RV is thin structure (compared to the LV) and therefore intrinsically more difficult to assess.
The current case was considered controversial within the editorial board, stimulating a lot of interest and debate also among the reviewers.
In light of the teaching value of debate all the reviewers' comments are reported below: Reviewer 1 felt that this case shows how T1 and T2 weighted images are usually not helpful to ruling in or out the diagnosis. Reviewer 2 highlighted that fibrofatty infiltration remains a histological diagnosis "on endomyocardial biopsy" even in the revised criteria, and that the new criteria de-emphasise minor regional wall motion abnormalities. Reviewer 3 underlined the challenge in interpreting LGE images correctly, recalling the controversy arisen over past published images. In particular, he suggested whether the apparent LGE along the inferior wall from ~4 to 5 O'clock (Figure 5) could be an artifact or local signal variation due to adjacent fat/effusion. He also felt that the apical LGE was not absolutely convincing. Reviewer 4 was not certain there is a focal RV aneurysm because when it is only shown on short axis,
through-plane motion is frequently the cause for the systolic displacement demonstrated (note RV inflow bulge on 4-chamber view); this is particularly true on a basal image (like the one provided in this case). He also felt that focal aneurysms should be more significant to differentiate subtle wall motion variability of the RV (present in >80% normal hearts) from true aneurysms. He agreed with Reviewer 3 that LGE is very questionable (if almost not believable) giving that it is extremely unlikely that LGE would be so extensive given the RV wall thickness. Also, it would be unusual that this degree to fibrosis would be present in someone so young (19yo). Reviewer 5 and Reviewer 6 agreed on considering this case a nice example of the role of CMR in diagnosing ARVC, as opposed to the other reviewers.
ARVC is a challenging and difficult diagnosis and even imaging experts can significantly differ in their conclusions.
Additional invited comments from international experts in the field were therefore requested.
We are extremely grateful to Dr Marcus, Dr Tandri, Dr Basso and Dr Thiene for having accepted our invitation, and for their very valuable contribution to the discussion.
INVITED COMMENTS 1) Dr Frank Marcus, University of Arizona, USA "This is not a typical case of ARVC. Unusual features are the fact that the LV function is significantly impaired. . There is biventricular involvement. This has been reported and particularly associated with desmoplakin abnormalities. The ECG shows Q waves in the inferior leads as is seen in inferior infarcts. This suggests that the inferior RV is devoid of myocardium. I conclude that she has a biventricular cardiomyopathy that may be an unusual form of ARVC. However, other causes of cardiomyopathy should be considered including sarcoidosis and myocarditis. A myocardial biopsy from the junction of the anterior free wall and the septum could be helpful or even a septal biopsy. An RV angiogram could also confirm or clarify the imaging abnormalities. Finally, commercial genetic analysis is now available in 3 laboratories in the US. In summary, I would search for other causes of this biventricular cardiomyopathy, but can't exclude ARVC".
2) Dr Hari Tandri, The Johns Hopkins University School of Medicine, Baltimore, USA
In response to Reviewer 3 : "You are right about the exaggerated LGE appearance. This is because part of the LGE is unsuppressed fat. Short axis images show a lot of intrapericardial fat which gives an overestimation of fibrosis. You are right about the infero-lateral LGE. This pattern is consistent with PKP2 related ARVD. I bet that this kid will be mutation positive for PKP2. I have been seeing this pattern in well phenotyped PKP2 lately and quite convinced that this is the case".
3) Dr Cristina Basso and Dr Gaetano Thiene, University of Padua, Italy "We reviewed the interesting and well documented case of ARVC/D in a 19 year old boy.
It is our opinion that all the examinations are in keeping with a diffuse biventricular form of ARVC/D, a condition which has been increasingly diagnosed since the advent of LE-CMR.
In particular, the 12 lead ECG show low voltages and T wave inversion in V1-V4 and flattening in V5-6, as well as Q wave and abnormal T wave in inferior leads.
We agree with Frank Marcus that possible phenocopies include cardiac sarcoidosis. However, the absence of conduction abnormalities and the apparently preserved septum would suggest to rule out sarcoidosis.
As far as the final comments by the authors, we would remind that, according to the 1994 original and 2010 revised criteria, a definite diagnosis of ARVC/D is fulfilled by two major or one major and two minor criteria or four minor criteria from different categories.
The case herein reported has 3 major criteria for ARVC/D (and not 4) belonging to the following categories (take in mind that criteria belonging to the same category cannot be summed) :
1. Global or regional dysfunction and structural alterations;
2. Repolarization abnormalities;
Unfortunately, the remaining 3 categories of Diagnostic Criteria, i.e. Tissue characterization of wall, Depolarization abnormalities, and Family history, are not informative, since:
- Tissue characterization of wall : although the new diagnostic tools LE-CMR and CARTO mapping are really useful in ARVC/D work up to detect areas of myocardial atrophy, they are not yet considered among diagnostic criteria, even in the revised 2010 ones. Only endomyocardial biopsy data are listed.
- Depolarization abnormalities: although epsilon waves are not evident, no SAECG was performed to search for late potentials
- Family history: before labeling a case as not familial, you should proceed further, and, besides simple collection of family history, you need clinical screening of first degree family members.
Genetic screening of desmosomal genes is highly recommended as well as family members clinical investigation".
Editor's teaching point: This case emphasizes that although CMR can be very helpful in assessing the RV anatomy, function and tissue characterization, both image acquisition and interpretation are challenging and represent a difficult task. CMR is not the definitive test to confirm the diagnosis and correlation with the Task Force Criteria is always recommended.
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