12 | Chapter 1 and SCD may also be the first clinical manifestation.11 The clinically overt stage is preceded by a “concealed phase” in which no, or only subtle electrical or structural disease manifestation can be identified. The “electrical phase“ is characterized by T-wave inversions and terminal QRS prolongation on electrocardiogram (ECG), premature ventricular complexes (PVCs) and ventricular tachycardia originating from the RV. In the “structural phase”, changes on tissue level lead to regional wall motion abnormalities and in the end-stage potentially heart failure.12 Diagnosis No single test has sufficient sensitivity and specificity to serve as gold standard for ARVC diagnosis. To standardize the clinical diagnosis, a combination of clinical tests was defined in the Task Force Criteria (TFC) from 1994, and later modified in 2010.13 Criteria were divided into six categories: structure/function, tissue characterization, repolarization abnormalities, depolarization abnormalities, arrhythmias, and family history. Criteria considered to have high specificity were classified as major, other criteria as minor. At least two major, 1 major with 2 minor, or 4 minor criteria are required for a definite diagnosis. In general, low specificity of abnormalities associated with ARVC confronts clinicians with the challenge of differentiating ARVC from conditions like idiopathic RV outflowtract tachycardia, cardiac sarcoidosis and other causes of a volume overloaded RV. (Table 1) Treatment and risk stratification With no curative treatment options, current therapeutic strategies aim for symptom reduction and prevention of disease progression and SCD. Restriction of intense sports activity is regarded important in both ARVC patients and family members at risk, since exercise has been shown to provoke arrhythmias and accelerate disease progression. Unfortunately, it remains unclear to what extent exercise should be reduced to prevent harmful effects, while maintaining the physical and mental health benefits of exercise in general.14,15 Despite limited supportive data, beta-blockers are currently recommended in all patients since adrenergic stimulation seems to play a role in provoking ventricular arrhythmias.16 A central component of clinical management of ARVC patients and family members at risk is consideration of an implantable cardioverter defibrillator (ICD). Patients who benefit most from an ICD are those who have had an episode of ventricular fibrillation or sustained ventricular tachycardia. It remains a clinical challenge to select patients who will benefit from primary preventive ICD implantation. Different multivariable models have been developed to assist clinicians in this decision, of which the ARVC risk calculator published in 2019 (www.ARVCrisk.com) is currently the most extensively validated model.17 This tool estimates the 5-year risk of developing a first episode of sustained ventricular arrhythmia in patients with a definite ARVC diagnosis according to the 2010 TFC. Family screening Since ARVC is an inherited cardiomyopathy, family members of ARVC patients may be at risk of developing the disease. With the identification ARVC-causing genetic variants, integration of targeted genetic testing into clinical practice is proliferating. Given the autosomal dominant inheritance, first-degree relatives have a 50% chance of carrying the genetic predisposition for ARVC. However, even in family members carrying the same pathogenic variant as the index patient, cardiac screening is a major challenge because of incomplete penetrance and variable disease expression. Since life-threatening arrhythmias can already occur early in the disease, detection of the earliest signs of disease manifestation in family members is an ongoing quest.
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