The use of imaging in the management and surveillance of Arrhythmogenic Cardiomyopathy – a review of the latest EACVI expert consensus document.10 April 2017
By: Victoria Pettemerides
In 2010, the original 1994 international Task Force criteria for the clinical diagnosis of Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/ARVD) was revised with an aim to improve diagnostic sensitivity and maintain specificity. [i] More recently, the European Association of Cardiovascular Imaging has released a consensus document giving recommendations for the use of multimodality imaging in the diagnosis, screening, follow up and risk assessment of Arrhythmogenic Cardiomyopathy.[ii] The latest recommendations will be reviewed and summarised here.
Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy associated with sudden cardiac death (SCD), ventricular arrhythmia, ventricular dysfunction and heart failure syndrome. Left ventricular involvement occurs in almost 50% of cases and some left ventricle dominant forms have been described. To take this into account the consensus group opted to use the term ‘Arrhythmogenic Cardiomyopathy’.
Arrhythmogenic cardiomyopathy is a rare disease with prevalence estimated between 1:2000 and 1:5000.[iii] It is characterised by either segmental or diffuse replacement of myocardium by fibrous and fatty tissue. This will start at the epicardium or mid myocardium and progressively extend to transmural replacement typically in the RV inferior, apical and infundibular walls. The LV involvement is usually confined to the posterolateral wall.
Disease causing gene mutations are found in approximately 60%, with desmosome gene mutations being the commonest (junction plakoglobin, desmoplakin, plakophillin-2, desmoglein-2, desmocollin-2). The pattern of inheritance is autosomal dominant but penetrance can be incomplete and expression variable.[iv] 25% of mutation gene carriers have compound or digenic heterozygosity which also helps to explain some phenotypic variability. Non desmosome gene mutations have been identified however the phenotypical features are not usually classical.
It is not yet fully clear how the disruption of cell junctions by abnormal desmosomal protein leads to the death, regeneration and replacement of myocardium with fibrous and fatty tissue. It has been postulated that the remodelling of ion channels and gap junctions could lead to the abnormal electrical conduction/arrhythmogenic nature of the disease.
Presentation and initial investigation:
Classically clinical presentation is with Ventricular Tachycardia precipitated by exercise. Patients describe an awareness of palpitations and light-headedness which can be distinguished from the heavy thump usually described with ventricular ectopic activity. The take home message from the consensus document is that ECG abnormalities will be the first manifestation found at investigation. Any possible Arrhythmogenic Cardiomyopathy structural abnormalities suggested by imaging modalities in a patient with a normal ECG ought to be considered suspicious and reviewed again. Mutation carriers may well have a normal ECG, however the risk of a life-threatening arrhythmia as the initial presentation in these patients is considered very low.
ECG abnormalities will reflect the area of cardiac involvement: T wave inversion in V1-V3 reflecting RV free wall involvement, T wave inversion V4-V6 reflecting LV involvement and inferior changes (II, III, aVF) reflecting involvement of the RV infero-posterior wall.
This is the first line imaging modality for the diagnosis of AC and is especially useful in the follow up of AC patients. It is widely available and well tolerated with little or no risk to the patient. However, owing to the RV shape, position and load dependency, quantitative and functional assessment can be difficult requiring specific expertise for its use in the diagnosis of AC.
Typically, RWMA or global RV dysfunction and dilatation is seen in AC. The 2010 Taskforce diagnostic criteria are based on: RV akinesia, dyskinesia or aneurysm identified by 2D echo with increased RVOT end diastolic measurements (>/32mm in parasternal long axis views or >/16mm in parasternal short axis views) or a fractional area change less than 33%.
The consensus group recommend a broader and systematic evaluation of the RV using both conventional 2D echo and where possible advanced echo techniques in addition to the above quantitative analysis. The group recommends routinely measuring the RV basal diameter (expected to be increased) and tricuspid annular plane systolic excursion, TAPSE (expected to be reduced) on conventional 2D TTE. In screening and follow up of early disease where more sensitive markers are needed, speckle tracking echo and global RV and LV strain assessment should be used. They acknowledge that although these parameters are not validated in larger studies, it will aid the diagnostic accuracy of AC.
3D Echo will allow the accurate measurement of RV and LV volumes. This is more useful in the later stages and follow up of AC patients rather than in the early phases. Measurement of volume in 3D can give a reasonably accurate assessment of ejection fraction. There are however limitations to this modality –it is less widely available and whilst normal volumes are known there is not yet any data specifically for AC patient volumes and risk stratification. Based on current data an RV ejection fraction <40-45% is abnormal.
Cardiac Magnetic Resonance:
Subtle RV regional structural and functional abnormalities are more easily detected by CMR than conventional echo. However, it is NOT the gold standard for the diagnosis of AC and it must be remembered that the diagnosis is dependent upon family history, ECG abnormalities, evidence of arrhythmia and histology If possible, as well as imaging criteria. As mentioned earlier, abnormalities seen on CMR with a normal ECG and normal Holter ought to be interpreted with caution. 2010 diagnostic criteria using CMR is the identification of: Regional RV akinesia, dyskinesia or dyssynchronous contraction with an increase in RV end diastolic volume indexed for body surface area (> 110ml/m2 for men and >100ml/m2 for women) or reduced RV systolic function (Ejection fraction <40%). Late gadolinium enhancement (LGE) and fat saturation technique is not included in the diagnostic criteria in 2010 as the recognition of fibro-fatty replacement was not felt to be a robust and reproducible parameter. The assessment of gadolinium enhancement is useful and would add weight to a suspected diagnosis but its pattern of distribution (sub-epicardial and mid wall enhancement) could be mistaken for other cardiomyopathies such as HCM, DCM or myocarditis. Additionally, there are no specific CMR criteria as yet for LV involvement
This is not included in the diagnostic criteria of 2010 however the consensus group recommend its use when echocardiography is inadequate and when CMR is not possible due to contraindications. RV/LV volume and function can be assessed as can the detection of fatty tissue replacement in the myocardium.
Whilst not included in the diagnostic algorithm nor widely used this may be a useful way to measure RV volumes, RV ejection fraction where echocardiography is inadequate or there are CMR contraindications.
Single-photon emission CT – SPECT:
1231-MIBG single photon emission CT has identified abnormal presynaptic myocardial sympathetic function both in heart failure patients and in AC patients with markedly higher risk of ventricular arrhythmia. Its use in the future may be as an extra individualised risk stratification tool but is currently a research tool.
In early disease, echocardiographic diagnosis can be difficult because changes are subtle with only mild RV hypokinesia and mild dilatation. The consensus group recommends the use of advanced echo techniques to help but adheres to the Task Force 2010 criteria that CMR ought to be used in the early detection and diagnosis. LGE should also be used but with recognition that it is not specific for AC.
As discussed earlier there is a wide genetic variability. Therefore, genetic testing should only be offered to those meeting phenotypic diagnostic criteria in order to help avoid the over interpretation of gene variants with unknown significance. Accidental finding of AC resembling pathology with a normal ECG and normal Holter should not be referred for genetic testing.
Risk stratification and ICD implantation:
There are no definitive evidence based imaging parameters to risk stratify for ICD implantation. Severely reduced RV and LV function are important risk factors and LV involvement is a strong risk factor. Individualised follow up, evaluation and risk stratification should be carried out.
The expert consensus group document provides a useful update of the diagnostic criteria set out in the Task Force review 2010 and gives additional recommendations for the use of different imaging modalities in the diagnosis, screening and follow up of Arrhythmogenic Cardiomyopathy. In addition, it gives recommendations to help differentiate between other arrhythmic conditions and acquired conditions such as sarcoid heart and athletes heart.
[i] Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Marcus FI et al. Circulation. 2010 Apr 6;121(13):1533-41. doi:10.1161/CIRCULATIONAHA.108.840827. Epub 2010 Feb 19.
[ii] Comprehensive multi-modality imaging approach in arrhythmogenic cardiomyopathy-an expert consensus document of the European Association of Cardiovascular Imaging. Haugaa KH et al. Eur Heart J Cardiovasc Imaging. 2017 Mar 1;18(3):237-253. doi:10.1093/ehjci/jew229.
[iii] Arrhythmogenic cardiomyopathy.
[iv] ARRHYTHMOGENIC RIGHT VENTRICULAR DYPLASIA. An article from the e-journal of the ESC Council for Cardiology Practice VOL.10,N°25 - 16 APR 2012
Prof. Josep Brugada and Dr. Juan Fernández-Armenta
Number of hits: 170 Add Comments