Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Definition
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited form of heart disease characterized pathologically by fibrofatty myocardial replacement and clinically by prominent ventricular arrhythmias and impairment of ventricular systolic function.
Etiology
It is thought to be an inherited disease usually with autosomal dominant inheritance and variable penetrance and phenotypes.
Pathophysiology
Progressive loss and fibrofatty replacement of right ventricular myocardium in ARVC may be due to apoptosis of cardiomyocytes, myocardial inflammation, genetically determined myocardial atrophy and possibly viral involvement.
A characteristic finding is replacement of the right ventricular anterolateral free wall myocardium by fatty or fibrofatty tissue extending from the epicardium towards the endocardium.
Fatty replacement of the myocardium may be diffuse or segmental. Transmural infiltration is often associated with increased wall thickness.
Other findings are saccular aneurysms of the apex, infundibulum or postero-inferior wall.
Islands of surviving myocardium in between fatty or fibrofatty tissue predispose to re-entrant tachycardia.
Epidemiology
ARVC has an estimated prevalence of 1 per 5000 in the population.
Clinical manifestation
The most common clinical presentation consists of ventricular arrhythmias and related symptoms/events, which include palpitations, syncopal episodes (mostly occurring during physical exercise), and cardiac arrest.
Sudden cardiac death (SCD) may occur unexpectedly in previously asymptomatic individuals, mostly young people and competitive athletes, with a previously undiagnosed ARVC.
Diagnostic approach (Image 1)
Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. (2020). [Illustration]. https://www.internationaljournalofcardiology.com/article/S0167-5273(20)33293-9/fulltext
Echocardiography findings
Echocardiography has variable sensitivity and specificity for the diagnosis of ARVC and therefore only forms a part of the complete diagnosis.
There are Major and Minor echocardiographic criteria that should be evaluated to support the ARVC diagnosis (Image 2).
The Echocardiographic Assessment of the Right Ventricle with particular reference to Arrhythmogenic Right Ventricular Cardiomyopathy – A Protocol of the British Society of Echocardiography. (n.d.). [Illustration]. https://www.bsecho.org/common/Uploaded%20files/Education/Protocols%20and%20guidelines/ARVC.pdf
1. Qualitative assessment of regional wall motion abnormalities- Akinesia, Dyskinesia of Aneurysm
PLAX- analysis of the anterior wall of the RV
PLAX RV inflow- analysis of the anterior and inferior walls of the RV
PSAX AV level- analysis of the outflow tract of the RV
PSAX PV level- analysis of inferior, lateral, anterior and septal walls of RV
PSAX Base, Mid, Apex- analysis of inferior, lateral, anterior and septal walls of RV
Video 1 ARVC, PLAX view of the severely dilated right ventricle with significantly reduced systolic function.
Video 2 ARVC, PLAX view, dilated RV with akinesis of basal part and mid ventricular akinetic aneurysm (probably due to lipomatous changes of the myocardium)
Video 3 ARVC, A4C view, dilated RV with akinesis of basal part and mid ventricular akinetic aneurysm (probably due to lipomatous changes of the myocardium). Only apical ¼ has effective contraction. Note the extensive trabeculation.
Video 4 ARVC, PSAX at the level of mitral valve - severely dilated RV with diffuse hypokinesis and reduced radial contractility.
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Video 5 ARVC, PSAX view at the level of ventricles of severely dilated right ventricle - note the minimal radial contractility of the RV. Electrode is seen in the RV.
Video 6 ARVC, PSAX at mid ventricular level - note the extensive trabeculation of the RV myocardium typical in ARVC. The RV is dilated and has severely reduced systolic function.
Video 7 ARVC, A4C view, dilated RV with severely reduced systolic function, basal akinesis
Image 3 ARVC, dilated RVOT with aneurysm, PSAX view - diameters of the aneurysm 11x3mm
Video 8 ARVC, severely dilated RV with aneurysm of the apical ⅓ associated with severe tricuspid regurgitation
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Video 9 ARVC, severely dilated RV, spherical remodellation with severe systolic dysfunction in a young patient. PLAX view
VIdeo 10 ARVC, severely dilated RV, spherical remodellation with severe systolic dysfunction. Note the pronounced trabeculation of the RV. Massive wide-open tricuspid regurgitation. A4C view
2. Assessment of right ventricle outflow tract (RVOT)
We should measure the RVOT in 2D echocardiography in the end diastole.
- RVOT PLAX should be measured in a perpendicular line from the RV anterior wall to the level of the aortic valve.
- PSAX AV level - Proximal RVOT measured from anterior aortic wall directly up to the RV free wall (at the level of the aortic valve)
- PSAX PV level - Distal RVOT measured just proximal to PV
Image 4 Normal values for RV chamber size
Adapted from: Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016 Apr;17(4):412. doi: 10.1093/ehjci/jew041. Epub 2016 Mar 15. Erratum for: Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233-70. PMID: 26983884.
Image 5 RVOT diameter measured in PLAX view - severely dilated RVOT to 56 mm (normal range 20-30mm)
Image 6 Proximal RVOT diameter measured in PSAX view at the level of aortic valve - dilated RVOT to 43 mm.
Image 7 Distal RVOT diameter measured in PSAX view at the level of aortic valve - RVOT dilated to 33 mm.
Image 8 Distal RVOT diameter measured in PSAX view at the level of aortic valve just proximal to the pulmonic valve - dilated to 29 mm.
3. Assessment of tricuspid regurgitation and TAPSE
Tricuspid regurgitation is often associated with ARVC due to dilation of the tricuspid annulus.
This only worsens the function of the right heart.
The TR is assessed in all available views.
The tricuspid valve is best visualised using the:
- PLAX of RV inflow
- PSAX at the level of the aortic valve
- apical 4 chamber view
- subcostal views
- TOE – 4 chamber view at 0 degree in the basal transesophageal and esogastric junction
In A4C view using M-mode the Tricuspid Plane Systolic Excursion (TAPSE) should be used to demonstrate longitudinal dysfunction.
TAPSE < 16mm is considered abnormal.
Video 11 Severe tricuspid regurgitation in ARVC, A4C view with colour Doppler - secondary TR due to dilation of the tricuspid valve (TV) annulus (diameter 63 mm), non-coaptation of TV leaflets. Large regurgitant jet fills the majority of the PA.
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Video 12 Severe (3/4) tricuspid regurgitation in ARVC due to dilation of the TV annulus, A4C view with colour Doppler - note the central regurgitant jet.
Video 13 ARVC, massive secondary tricuspid regurgitation with TV annulus dilation so extensive there is no central coaptation of TV leaflets, resulting in wide-open tricuspid regurgitation. A4C view with colour Doppler.
Image 9 CW Doppler measurement of severe TR, A4C view - observe the dense signal and triangular shape of the CW signal. Peak velocity 2,35 m/s.
Image 10 Tricuspid Plane Systolic Excursion (TAPSE) in ARVC, significantly reduced longitudinal contraction - TAPSE 12 mm
4. Assessment of right ventricle diameter
In Apical 4CH Focused RV view we measure the Right ventricle diameter.
There are not any specific values to diagnose ARVC but all of RV measurements should be used to demonstrate dilatation.
RVD1 > 42mm, RVD2 > 35mm and RVD3 > 86mm are abnormal.
RVD1 – Basal RV diameter in the first third of the RV
RVD2 – Mid RV diameter in the middle third of the RV at the level of the LV papillary muscles
RVD3 – RV length from tricuspid annulus to the RV apex
Image 11 Assessment of right ventricle diameter in ARVC - severely dilated RV - RVD1 - 55mm, RVD2 - 59mm, RVD3 - 97 mm
Image 12 Assessment of right ventricle diameter in ARVC - severely dilated RV, RVD1 - 68 mm, RVD2 - 55 mm, RVD3 - 101 mm
5. Assessment of Fractional Area Change (FAC)
To measure FAC trace around the endocardium of the RV lateral wall at end diastole and end systole
FAC ≤ 33% in the presence of regional RV akinesia, dyskinesia or aneurysm is a major criterion
FAC > 33% to ≤ 40%in the presence of regional RV akinesia or dyskinesia is a minor criterion.
Image 13 Assessment of Fractional Area Change (FAC) in ARVC - the endocardium is traced in the end diastole (left) and end systole (right). The FAC is calculated at 21% - severely reduced systolic function.
Management
An implantable cardioverter-defibrillator (ICD) is recommended for secondary prevention of sudden cardiac death in patients with sustained ventricular tachycardia or ventricular fibrillation and for primary prevention in high-risk patients.
Antiarrhythmic therapy is recommended as an adjunct therapy to implantable cardioverter-defibrillator (ICD) in patients with frequent appropriate device discharges.
Beta-blockers are generally considered the first line of drug therapy. Beta-blocker therapy should be considered in all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC) irrespective of arrhythmias.
Antiarrhythmic agents include flecainide, propafenone, sotalol, and amiodarone, alone or in combination.
Sotalol is the most effective drug for inducible or noninducible ventricular tachycardia.
References
1. Towbin JA, McKenna WJ, Abrams DJ, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm. 2019 Nov;16(11):e301-e372. doi: 10.1016/j.hrthm.2019.05.007. Epub 2019 May 9. PMID: 31078652.
2. Corrado, D., Basso, C., & Judge, D. P. (2017a). Arrhythmogenic Cardiomyopathy. Circulation Research, 121(7), 784–802. https://doi.org/10.1161/circresaha.117.309345
3. Corrado D, Perazzolo Marra M, Zorzi A, Beffagna G, Cipriani A, Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Anastasakis A, Asimaki A, Bucciarelli-Ducci C, Haugaa KH, Marchlinski FE, Mazzanti A, McKenna WJ, Pantazis A, Pelliccia A, Schmied C, Sharma S, Wichter T, Bauce B, Basso C. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. Int J Cardiol. 2020 Nov 15;319:106-114. doi: 10.1016/j.ijcard.2020.06.005. Epub 2020 Jun 16. PMID: 32561223.
