Phenotypes in Arrhythmogenic Cardiomyopathy

Arrhythmogenic Cardiomyopathy was better known as Arrhythmogenic Right Ventricular Dysplasia or ARVD and sometimes as Arrhythmogenic Right Ventricular Cardiomyopathy or ARVC earlier. When left ventricular [1] and biventricular involvement became increasingly recognized, the terminology has been revised to Arrhythmogenic Cardiomyopathy. A study published in JACC has compared the phenotypic expression and clinical outcomes in patients with arrhythmogenic cardiomyopathy [2]. Of the 446 patients, 44% had arrhythmogenic right ventricular cardiomyopathy, while 23% had arrhythmogenic left ventricular cardiomyopathy. 33% had biventricular form of arrhythmogenic cardiomyopathy.

Those with right ventricular and biventricular phenotypes had significantly higher incidence of life threatening arrhythmias compared to the left ventricular phenotype of arrhythmogenic cardiomyopathy. Heart failure, heart transplantation and death by cardiac causes were more often seen in individuals with  biventricular phenotype compared to isolated left or right ventricular phenotype.

Arrhythmogenic cardiomyopathy is a heritable disease with myocyte necrosis and fibrofatty replacement leading to ventricular dyfsunction and life threatening ventricular arrhythmias. Sometimes arrhythmogenic cardiomyopathy patients can present with acute chest pain and elevation of myocardial enzymes and has been called as ‘hot phase’. These require differentiation from acute myocardial infarction and have normal coronary arteries [3]. Higher incidence of hot phases were noted in left ventricular and biventricular phenotypes.

PKP2 (plakophilin-2) mutations dominated in ARVC phenotype while DSP (desmoplakin) mutations predominated in ALVC forms. Those with PKP2 mutations had reduced life threatening arrhythmia free survival and higher arrhythmic risk than DSP group.

References

1. Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D, Pennell DJ, McKenna WJ. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol. 2008 Dec 16;52(25):2175-87. doi: 10.1016/j.jacc.2008.09.019. PMID: 19095136.
2. Bariani R, Rigato I, Celeghin R, Marinas MB, Cipriani A, Zorzi A, Pergola V, Iliceto S, Basso C, Marra MP, Corrado D, Gregori D, Pilichou K, Bauce B. Phenotypic Expression and Clinical Outcomes in Patients With Arrhythmogenic Cardiomyopathies. J Am Coll Cardiol. 2024 Feb 27;83(8):797-807. doi: 10.1016/j.jacc.2023.12.015. PMID: 38383094.
3. Bariani R, Cipriani A, Rizzo S, Celeghin R, Bueno Marinas M, Giorgi B, De Gaspari M, Rigato I, Leoni L, Zorzi A, De Lazzari M, Rampazzo A, Iliceto S, Thiene G, Corrado D, Pilichou K, Basso C, Perazzolo Marra M, Bauce B. ‘Hot phase’ clinical presentation in arrhythmogenic cardiomyopathy. Europace. 2021 Jun 7;23(6):907-917. doi: 10.1093/europace/euaa343. PMID: 33313835; PMCID: PMC8184227.