ABC | Volume 112, Nº1, January 2019

Elias Nero et al ARVC/D - Diagnosis and treatment Arq Bras Cardiol. 2019; 112(1):91-103 Review Article An observational study evaluated the clinical impact of ICD in the natural history of ARVC/D patients. At an average follow- up of 3.3 years, 24% of the patients had as an arrhythmic manifestation an episode of VF/VFL that would have been fatal in the absence of an ICD. 26 Despite these results, it is important to note that the survival benefit with ICD is obtained at the expense of a high prosthesis cost, and a significant rate of complications during follow-up, mainly related to the occurrence of inappropriate therapies around 4%/year and changes in the electrodes. 33 Inappropriate interventions occur between 10% and 25% of the patients, mainly in young patients and usually due to sinus tachycardia or atrial tachyarrhythmia (Figure 1C). The high rate of adverse events related to the electrodes can be explained by the peculiar pathophysiology of ARVC/D that leads to progressive loss of myocardium and to fibrous and fatty replacement that can both generate difficulties in locating a suitable place to implant the leads, and affect the thresholds of command and sensitivity during clinical follow‑up. 4,5 Another aspect is that it became evident that ICDs may be inappropriately implanted in patients with a false diagnosis of ARVC/D based on misinterpretation of CMR studies. 4,5 Unicameral ICDs are recommended to minimize the risk of complications related to prolonged use of this device, especially in young patients. Although the number of inadequate interventions can be reduced by a dual chamber detection system, the additional lead predisposes to a greater risk of short‑and long-term complications. 22 Anti-tachycardia pacing is highly successful in terminating ventricular arrhythmia, and should be programmed into all devices. 42 The role of the subcutaneous ICD is under investigation. Based on the results of studies that defined independent predictors of major arrhythmic events (i.e. SAD, cardiac arrest due to VF, sustained VT and appropriate ICD interventions), ITF proposed an ICD indication flowchart based on three categories (Figure 4). 4,5,34 The recommendations for the implantation of the ICD for each risk category are based not only on the statistical risk, but also on the general health, socioeconomic, psychological and adverse factors of the device. Heart transplant It is rare for a ARVC/D patient to require a heart transplant. Transplantation would be indicated as final therapy in cases of severe heart failure, and when not responsive to pharmacological treatment and resynchronization therapy (in those patients with significant LV involvement), or in patients with intractable arrhythmias (eg, incessant VT, or VF storms refractory to catheter ablation and ICD therapy). 4,5 Prevention of progression The last aspect to be considered in patients with ARVC/D is the prevention of disease progression. It is important to note that no study examined aspects that signal the evolutionary characteristics and the rate of progression of ARVC/D. Progression is slow but steady. It is suggested that the restriction of physical exercise may interfere with the rate of disease progression. 15 A definitive curative treatment will require a deeper understanding of the biological mechanisms and environmental factors involved in the pathogenesis of ARVC/D. 5 Future perspectives Significant advances were achieved if we consider the 30 years or more of the diagnosis of this pathology. However, given its rarity, many gaps persist. It is possible to define some areas of interest that will allow better clinical management of patients and definition of the population at risk of sudden death: • Although not yet routinely available, the future possibility of genetic screening of patients and family members with clinical suspicion of ARVC/D may become of extreme relevance with potential implications for understanding the pathogenesis and management of affected individuals. • Further refinement in the detection of morphological abnormalities will allow a greater refinement in the algorithm for the identification of ARVC/D carriers and a better understanding of their natural history. An improvement in imaging techniques (magnetic resonance imaging and echocardiography), and the possibility of MR follow-up in patients who received MR-compatible ICD implantation. • Studies that try to analyze the phenotype-genotype correlation may clarify the natural history of the disease, and the greater propensity for the development of malignant arrhythmias and, therefore, define the best time to initiate a medical intervention. The denomination of this cardiomyopathy has been discussed for years. The debate between naming it RVAD or RVAC is the representation of two different views of its pathophysiology, degenerative process or developmental abnormality. Probably both visions are involved; although the terminology initially proposed by Fontaine – “dysplasia” - is probably questionable, this term has been used and accepted for 40 years, and it will persist, incorporated to the history and description of this cardiomyopathy. Tribute Guy Fontaine died on March 7, 2018 at the age of 82. He pioneered modern electrophysiology and cardiac arrhythmia therapy; a visionary investigator andmentor for many electrophysiologists. Fontaine began his contributions by studying the first cardiac pacemakers in the 1960s, and pioneered the study of catheter arrhythmias by introducing surgical cardiac mapping in 1972 for ablation of severe arrhythmias, WPW syndrome, and ventricular tachycardias, which allowed the recognition and study of RVAD, its main subject of research. He introduced catheter ablation with fulguration procedures, and studied 3D mapping methods thoroughly. Guy Fontaine is the author of more than 700 manuscripts and book chapters. He received numerous international awards for his contributions and continued active until his last day of life, despite of a severe disabling illness. 10