#4 | January 2024

Arrhythmogenic right ventricular cardiomyopathy

This is the third of our series of articles on cardiomyopathies, and concerns arrhythmogenic cardiomyopathy (AC). This describes any form of non-hypertrophic, progressive cardiomyopathy characterised by fibro-fatty infiltration of the ventricular myocardium [1]. It has, as the quote below implies, an inherited familial pattern.

"(...) diseases may be handed down from parents to children (and ...) disorders of the heart can be handed down (…) from the very moment of conception (...)".

Giovanni Maria Lancisi (1654–1720) on arrhythmogenic cardiomyopathy [2]

Overview

  • It is relatively rare, causing ~1% of all cardiomyopathies and has a prevalence of 1:2,500 to 1:5,000. In the UK, this equates to ~13,000 to 26,000 prevalent cases. The prevalence is higher in parts of Italy (Padua and Venice "Venetian disease"), and Greece (particularly the Island of Naxos where this has given rise to the term "Naxos disease" [3] [4].
  • According to Delmar and McKenna, AC is a disease that bridges the gap between those of inherited arrhythmia and heart muscle disorders [5].
  • The disorder accounts for 5% to 10% of sudden unexplained deaths in individuals less than 65 years of age, with overt disease commonly manifesting in early adulthood.
  • Onset before age 15 is rare and as per Groeneweg (2015) onset before 10 never occurs, peak manifestation is around age 25 [6].
  • However, one-fifth of all AC patients present after age 50, and ~3% after 65. Such late presentation does not confer a benign prognosis and is associated with high arrhythmic risk [7].
  • Males are more effected than females by a ratio of 2.7: 1 [8].
  • Medical understanding of the familial nature of arrhythmogenic cardiomyopathy (AC) has a surprisingly long history. The Italian physician Giovanni Maria Lancisi (1654–1720) reported on four generations of a family in the 18th century who had palpitations, heart failure, and sudden death. Autopsies of the affected individuals showed classically right sided structural abnormalities of the right side of the myocardium [2].
  • In 1977 Guy Fontaine while investigating patients with ventricular tachycardia noted that they had a condition characterised by fatty replacement of the free wall of the right ventricle, which was the site of origin of the tachycardia, whereas the left ventricle generally appeared normal [9]. This led in 1982 to "arrhythmogenic right ventricular dysplasia" (ARVD), being clinically described as a distinct disease characterised by the replacement of myocytes with that of "fibro-fatty" tissue, and recognition that the process usually triggered by desmosomal dysfunction. Mutations in genes that encode cardiac desmosome cause 60% of incidence [10].

Desmosomes

These are protein chains that link and stick neighbouring cells together. They exist throughout the body but are found in organs or tissues, such as the heart and skin, which are subject to significant mechanical force. In people with AC, these proteins have not developed properly and cannot keep the heart muscles together under stress. The damage resulting from this abnormality causes the heart muscle cells to die and become fibrous and scarred [11].

In established disease, aneurysmal dilatation is present in 50% of the cases. An aneurysm occurs in the diaphragm, apical area, and infundibulum, known as the triangle of dysplasia. The left ventricle is involved in 50% to 67% of cases. Involvement of the left ventricle suggests a poor prognosis [8].

Diagnosis

AC usually presents with palpitations, syncope, or cardiac arrest. Then, premature ventricular complexes (PVC) or ventricular tachycardia (VT) with LBBB morphology and T-wave inversion in V1- V3 leads on basal electrocardiogram (ECG) are the most common index of suspicion. Less-common presentations are RV or biventricular dilatation, with or without heart failure symptoms, mimicking dilated cardiomyopathy. Clinical manifestations vary with age and stage of disease.

Men usually develop a more severe phenotype, most likely because of the effect of vigorous sporting activity on disease onset and progression and influence of sex hormones.

Other diagnosis such as idiopathic RV outflow tract tachycardia, myocarditis, sarcoidosis and congenital heart diseases need to be ruled out

The ‘classic phenotype’ presents as:

  • Right precordial T wave inversion and arrhythmia in right ventricle
  • Familial instances of ventricular fibrillation and sudden cardiac death
  • Echocardiogram shows severe right ventricle dilatation and systolic dysfunction
  • Reduced right ventricular function

Clinical presentation is characterised by ventricular arrhythmias and risk of sudden death.

Underwriting considerations

Traditionally all applicants with established and diagnosed AC have been declined insurance due to the risk of sudden death and long-term risk of heart failure; however, recent studies have shown if individuals are treated (with implantable cardiac devices), monitored regularly and adequate risk stratification is followed some applicants can be offered terms albeit with heavy extra mortality. Morbidity products however remain problematic.

Individuals identified through family history and genetic studies who remain asymptomatic can also be offered terms albeit with appropriate ratings.

Author

Paul Edwards

Underwriting Research & Systems Development Manager

Hannover Re UK Life Branch

References

  1. Corrado D et al. International Experts, Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis, European Heart Journal, ehz669, 2019. Available from: https://doi.org/10.1093/eurheartj/ehz669. Viewed on 16 January 2024.
  2. Marrone D, Zampieri F, Basso C, Zanatta A, Thiene G. History of the discovery of Arrhythmogenic Cardiomyopathy. Eur Heart J. 2019 Apr 7;40(14):1100-1104. doi: 10.1093/eurheartj/ehz145. PMID: 30955041.}
  3. Corrado D, Basso C, Judge D.P. Arrhythmogenic Cardiomyopathy. Circulation Research Volume 121, Issue 7, 15 September 2017; Pages 784-802. Available from https://doi.org/10.1161/CIRCRESAHA.117.309345. Viewed on 16 January 2024.
  4. Fontaine, G et al. Arrhythmogenic Right Ventricular Cardiomyopathies:Clinical Forms and Main Differential Diagnoses. Circulation. 1998;97:1532–1535.
  5. Delmar M & Mckenna W.J. The cardiac desmosome and ARCM: from gene to disease Circulation Research, Sept, 2010.
  6. Groeneweg J.A. Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members Circulation: Cardiovascular Genetics Vol. 8, No. 3, 2015.
  7. Bhonsale A. Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation Heart Rhythm. 2017 Jun;14(6):883-891. doi: 10.1016/j.hrthm.2017.02.013. Epub 2017 Feb 12.
  8. Shah SN, Umapathi KK, Oliver TI. Arrhythmogenic Right Ventricular Cardiomyopathy. [Updated 2019 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470378/. Viewed on 16 January 2024.
  9. Marcus F.L. Profiles in Cardiology. Guy Fontaine: A Pioneer in Electrophysiology Clin. Cardiol. 21, 145-146 (1998).
  10. Calkins H, Corrado D & Marcus F. Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy Circulation. 2017;136:2068–2082. DOI: 10.1161/CIRCULATIONAHA.117.030792.
  11. British Heart Foundation. Inherited heart conditions: Arrhythmogenic right ventricular cardiomyopathy. 2009. Available from: https://www.bhf.org.uk/informationsupport/publications/heart-conditions/m111e-inherited-heart-conditions---arrhythmogenic-right-ventricular-cardiomyopathy. Viewed on 16 January 2024.

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