Arrhythmogenic cardiomyopathy

Formerly known as Arrhythmogenic Right Ventricular Cardiomyopathy or Arrhythmogenic Right Ventricular Dysplasia.

Introduction

  • It is a heritable heart-muscle disorder that predominantly affects the right ventricle, but variants affecting the left ventricle (even predominantly) have been described and the name of the disease has therefore been changed to reflect current state of knowledge

  • The underlying pathological process is replacement of myocardium with fibrous and fatty tissue forming a fibrofatty scar, 

  • This change is most frequently localised in the so-called “triangle of dysplasia” formed by the inflow tract (sub tricuspid region), outflow tract (infundibular region), and apex of the right ventricle. It is a result of an inflammatory process and progresses over time. Exercise further accelerates this process

  • Subsequently, potentially life threatening ventricular arrhythmias may develop. Disease progression may result in right or biventricular heart failure
  • In most cases it is caused by mutations in genes encoding desmosomal proteins (plakoglobin), desmoplakin, plakophilin-2, desmoglein-2 and desmocollin-2

  • Clinical presentation includes symptoms such as palpitations or effort-induced syncope  typically in adolescents or young adults

  • Diagnosis consists of a combination of family history, clinical presentation, ECG (including signal averaged ECG), echocardiography, MRI, right ventricular angiography and end-myocardial biopsy.

ECG characteristics

There are two categories of ECG characteristics that form diagnostic criteria (some are major criteria - bold, some are minor, presented criteria are simplified):

1) Repolarization, depolarisation and conduction abnormalities

  • Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in individuals  14 years of age (in the absence of complete right bundle-branch block QRS  120 ms)

or

  • Inverted T waves in leads V1 and V2 in individuals >14 years of age (in the absence of complete right bundle-branch block) or in V4, V5, or V6

or

  • Inverted T waves in leads V1, V2, V3, and V4 in individuals >14 years of age in the presence of complete right bundle-branch block
  • Epsilon wave (reproducible low-amplitude signals between end of QRS complex to onset of the T wave) in the right precordial leads (V1 to V3)
  • Late potentials on signal averaged ECG

2) Arrhythmias

  • Nonsustained or sustained ventricular tachycardia of left bundle-branch morphology with superior axis (negative or indeterminate QRS in leads II, III, and aVF and positive in lead aVL)
  • Nonsustained or sustained ventricular tachycardia of RV outflow configuration, left bundle-branch block morphology with inferior axis (positive QRS in leads II, III, and aVF and negative in lead aVL) or of unknown axis
  • 500 ventricular extrasystoles per 24 hours (Holter)


Picture 1 Epsilon wave

Management

  • Current therapeutic approaches to ARVC are palliative and partially alleviate symptoms and the risk of sudden cardiac death but do not prevent the development or progression of the disease process
  • Important recommendation is restriction from intense sports activity
  • Pharmacotherapy includes beta blockers and for patients with arrhythmias a combination of beta blockers and amiodarone/sotalol
  • Patients with sustained, monomorphic ventricular tachycardia are indicated for catheter ablation (endo and/or epicardial approach)
  • Patients who have had an episode of ventricular fibrillation or sustained ventricular tachycardia probably benefit from ICD implantation

ECG 1 T wave inversions in leads V1-V3 in a patient with Arrhythmogenic cardiomyopathy

ECG 2 Epsilon wace best visible in lead V1 but present in leads V1-V3, T wave inversions in V1-V4

ECG 3 Epsilon waves in leads V1-V3, T wave inversions in V1-V4

Picture 2 Carto 3D mapping revealed extensive scar (low voltage area) on a lateral wall of right ventricle (from tricuspid annulus to RVOT) - 3 types of ventricular tachycardias (KT 1, KT 2, KT 3) provoked during EP study


Picture 3 Mid diastolic potentials present during VT (arrows)

Picture 4 Termination of arrhythmia during ablation

References

  1. Jarcho, John A., Domenico Corrado, Mark S. Link, and Hugh Calkins. 2017. “Arrhythmogenic Right Ventricular Cardiomyopathy”. New England Journal Of Medicine 376 (1): 61-72. https://doi.org/10.1056/NEJMra1509267.
  2. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010 Apr 6;121(13):1533-41. doi: 10.1161/CIRCULATIONAHA.108.840827. Epub 2010 Feb 19. PMID: 20172911; PMCID: PMC2860804.
  3. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekvål TM, Spaulding C, Van Veldhuisen DJ; ESC Scientific Document Group. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015 Nov 1;36(41):2793-2867. doi: 10.1093/eurheartj/ehv316. Epub 2015 Aug 29. PMID: 26320108.