Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease of the cardiac muscle characterized by right ventricular dysfunction (global or regional) with or without left ventricular (LV) involvement in the presence of histological evidence of the disease and/or electrocardiographic abnormalities according to published criteria.¹

ARVC has age-dependent penetrance and is mainly characterized by episodes of ventricular arrhythmia that can progress to sudden cardiac death (SCD). The estimated prevalence ranges from 1:2,000 to 1:5,000, with a predominance in the Caucasian population and in people who practice strenuous exercise or competitive sports. Despite its low prevalence, ARVC represents approximately 5–20% of CSM cases in young people.²

Diagnosing ARVC is often difficult due to its heterogeneous clinical presentation, highly variable intra- and interfamilial expression, and incomplete penetrance.²; Right ventricular (RV) hypertrophy also occurs in athletes, making the diagnosis more challenging in this population.^3,4

A 47-year-old female marathon runner with no family history of CSM was admitted to the emergency department reporting palpitations and presyncope. Admission electrocardiography (ECG) showed ventricular tachycardia (VT) with a left bundle branch and lower axis block morphology (Figure 1A) for which she was subjected to electrical cardioversion (ECV). Post-ECV ECG showed sinus rhythm with precordial T-wave inversion in V1-V4 (Figure 1B). Findings of laboratory tests, including myocardial necrosis markers, were normal. Echocardiography (ECHO) showed enlarged right cardiac chambers and RV systolic dysfunction (reduced tricuspid annular plane systolic excursion and strain) (Figures 2 and 3). Cardiac catheterization revealed no obstructive coronary disease. The patient was discharged with instructions to suspend physical activity and undergo cardiac magnetic resonance (CMR). However, three months later she was readmitted with VT and hemodynamic instability and again underwent ECV. CMR showed RV with moderate dilation (RV end-diastolic volume index, 114 mL/m²;RV end-systolic volume index, 64 mL/m¹;), mild right ventricular systolic dysfunction (right ventricular ejection fraction, 43%; reference value, >45%), areas with dyskinesia and microaneurysm formation in the RV inferior wall, and dyskinesia in the RV outflow tract. The LV had preserved dimensions (LV end-diastolic volume index, 90 mL/m²; LV end-systolic volume index, 38 mL/¹;) (Figure 4 and Table 1).

Considering these findings and using the Task Force Criteria (TFC-2010), the patient was diagnosed with ARVC, for which an implantable cardioverter defibrillator (ICD) and amiodarone and beta-blocker therapy were indicated. The patient is currently without complaint and followed on an outpatient basis.

In 1994, the World Health Organization (WHO) classified ARVC as a non-ischemic cardiomyopathy. The condition generally manifests between the second and fourth decades of life.⁵ The most common clinical presentation is palpitations or exertional syncope. The clinical course of ARVC is characterized by arrhythmic events, which can lead to CSM and affect biventricular systolic function.³

RV hypertrophy is a common phenotypic expression and an essential component of the ARVC diagnosis. However, this finding is often seen in benign clinical conditions such as athlete’s heart. RV hypertrophy has been described in imaging studies of a large proportion of athletes, with more accentuated remodeling in resistance exercises. In these cases, RV hypertrophy may overlap with pathological dilation in patients with ARVC, making the diagnosis even more challenging.³

The diagnosis of ARVC is based on the TFC-2010, which combines family history and electrophysiological, morphofunctional, and histological criteria. Patients with four points are diagnosed with ARVC, while those with three points are identified as probable ARVC carriers, knowing that the major criterion is worth two points and the minor criterion is worth one point.⁶

Structural and functional assessments are essential to the diagnosis of ARVC. The initial investigation consists of non-invasive tests (ECG, high-resolution ECG [HRECG], ECHO and/or CMR, and 24-hour Holter monitoring).²

T-wave inversion in V1-V3 is the most common ECG finding in ARVC (up to 83% of patients) and a major criterion for its diagnosis.^2,7 Although ECG analysis is essential in the initial stratification, about 12% of patients with ARVC may have normal ECG findings, reinforcing the need for a diagnostic evaluation based on the TFC-2010.²

ECHO is the initial test in ARVC investigations. Findings suggestive of ARVC include global or segmental ventricular wall abnormalities associated with cavity dilation (mostly right) and RV hypertrophy with systolic dysfunction.² Systolic function assessments must be based on several parameters, as decreased fractional area change has been described in athletes, showing the importance of strain use.⁸

CMR assesses morphofunctional abnormalities and tissue characterization using late gadolinium enhancement, providing information on the presence and amount of fibrofatty replacement in the myocardium.^4,6 In addition to the parameters included in the TFC-2010, other characteristic ARVC abnormalities can be visualized, such as RV microaneurysms. Better accuracy (98%) is evidenced when segmental contractility changes and signs of pre- and postcontrast abnormalities (including LV fatty infiltration and late enhancement) are considered together.⁹

Twenty-four-hour Holter monitoring quantifies the number of ventricular extrasystole episodes and accesses the morphology of the arrhythmia, which may suggest its site of origin. The presence of ≥ 500 ventricular extrasystole episodes is considered a minor criterion.⁷

Endomyocardial biopsy is not routinely indicated for all patients with suspected ARVC; rather, it should be used only for probands with the sporadic form of ARVC and predominant LV involvement when the final diagnosis depends on the histological exclusion of phenocopies such as chronic myocarditis, sarcoidosis, or other myocardial disorders.⁴

Although the presence of mutation is part of the TFC-2010, the test results should be analyzed carefully, as a negative test does not exclude the possibility of disease and a positive result should lead to differentiation between causal mutations and non-pathogenic variants. Therefore, genotyping is used to identify the mutation considered causal in probands with phenotypic diagnostic criteria.⁹

The clinical management of ARVC aims to reduce the risk of SCD and improve quality of life by alleviating arrhythmic and heart failure symptoms.⁴ Sports activity increases the risk of SCD in adolescents and young adults with ARVC. Thus, it is important to highlight that these patients should not participate in competitive or endurance sports (class I); rather, they should practice only low-intensity recreational sports (class IIa).²

Current therapeutic options for ARVD include lifestyle changes, beta-blockers, antiarrhythmics, catheter ablation, ICD, and heart transplantation. Beta-blocker therapy should be instituted empirically in all patients with a clinical diagnosis of ARVC due to its ability to reduce the risk of ventricular arrhythmia and prevent myocardial disease progression.^2,7

Antiarrhythmic therapy should be considered adjunctive therapy to ICD in patients with multiple appropriate therapies (class I) and may be considered in patients with frequent ectopic activity and/or non-sustained VT (NSVT; class IIa).^2,6

The natural history of ARVC is characterized by the risk of CSD, hence the importance of stratifying patients by need for an ICD, which should be recommended in ventricular fibrillation and sustained VT (class I) and considered in the presence of unexplained syncope, NSVT, and severe RV or LV dysfunction (class IIa).^2,7

Cases such as this of ARVC in a marathon runner are difficult to diagnose, highlighting the importance of the integrated analysis of clinical, electrocardiographic, and morphofunctional factors. It is essential to be aware of physiological responses in athletes, paying attention to the reference values for this group (Table 2), to minimize diagnostic errors.