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Clinical presentation is characterized by ventricular arrhythmias at risk of sudden death. More rarely, right ventricular or biventricular dysfunction leading to heart failure is reported
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Generally referred as right ventricular disease, recognition of left-dominant and biventricular subtypes prompted the use of the broader term AC.
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Effort is a trigger of disease onset and progression as well as ventricular arrhythmias.
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Disease causing genes mostly encode for desmosomal proteins, although
Diagnostic Criteria, Genetics, and Molecular Basis of Arrhythmogenic Cardiomyopathy
Section snippets
Key points
Clinical features
Clinical manifestations vary with age and disease stage. Despite the similar prevalence of mutation carriers in both genders, the clinical expression of the disease is usually more severe in men, with a higher prevalence of male than female patients who fulfill the diagnostic criteria (up to 3:1).3, 5 Palpitations, syncope, and cardiac arrest are common symptoms in young adults or adolescents, and the most typical signs of AC are ventricular arrhythmias with left bundle branch block (LBBB)
Diagnostic criteria
Because there is no single gold standard, AC diagnosis requires multiple criteria, combining different sources of diagnostic information, such as morphofunctional (by echocardiography and/or angiography and/or cardiac magnetic resonance [CMR]), histopathological on endomyocardial biopsy, ECG, arrhythmias, and familial history, including genetics (Fig. 1).
The original diagnostic criteria15 were revised in 201016 to improve diagnostic sensitivity, by maintaining diagnostic specificity (Box 1).
Genetics
Although AC has been recognized as an inherited disease since the 1980s,29 the first disease-causing gene was identified in 2000, when the investigations carried out on a similar disorder in the Naxos Island marked the turning point in the understanding of the genetic background. In a cohort of people with palmoplantar keratoderma, wooly hair, and AC cosegregating in a recessive pattern, a haplotype on chromosome 17q21 was first identified, and further analysis led to the discovery of a
Pathogenesis
Experimental animal and cellular models are useful tools to explore how mutant desmosomal proteins lead to cardiomyocyte death and subsequent repair with fibrous and fatty tissue.4, 7, 60, 61
Future perspectives
The most important goals of clinical management of AC patients are sudden cardiac death prevention and improvement quality of life by decreasing or suppressing palpitations, VT recurrences, or ICD discharges.12 Current therapeutic approaches, which are discussed in detail elsewhere and out of the scope of this review, regard lifestyle modifications, pharmacologic treatment, catheter ablation, ICD implantation, and exceptionally, heart transplantation. However, they are all palliative tools of
Acknowledgments
This work has been supported by TRANSAC, University of Padua Strategic Grant CPDA133979/13, Padua, Italy; Registry for Cardio-Cerebro-Vascular Pathology, Veneto Region, Venice, Italy; Target Project, Regional Health System (RF-2014-00000394), Venice, Italy; PRIN Ministry of Education (2015ZLNETW), University and Research, Rome, Italy.
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2021, International Journal of CardiologyCitation Excerpt :Arrhythmogenic Cardiomyopathy (AC) is a familial heart disease at risk of stress-related arrhythmic sudden cardiac death (SCD) in the young and athletes [1,2]. In about 50% of genetically diagnosed cases, AC is caused by mutations in desmosomal genes, while the remainder patients either carry pathogenic variants in genes with various functions (i.e. ion channels, sarcomeric and signaling proteins) or are mutation-negative in standard test panels [3–5]. AC diagnosis is based on clinical/pathologic criteria, including morpho-functional cardiac abnormalities, tissue characterization on endomyocardial biopsy, electrocardiographic changes, ventricular arrhythmias and family history [6].
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Disclosure Statement: The authors have nothing to disclose.