Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive loss of cardiomyocytes, fibrofatty replacement of the myocardium, ventricular electrical instability, and risk of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. The classic phenotype predominantly involves the right ventricle, especially the outflow tract, free wall, and infero-apical region, but the modern view recognizes that the same disease biology may also involve the left ventricle or both ventricles. For this reason, the broader term arrhythmogenic cardiomyopathy (ACM) describes a continuum in which the classic right-sided form represents one of the most recognizable expressions, not the only possible one.
The disease is rare, but has major clinical relevance because it may present with ventricular arrhythmias in adolescents, young adults, or apparently healthy athletes. Epidemiological estimates vary according to the population and diagnostic criteria, with approximate prevalences ranging from 1:2000 to 1:5000 in the general population. Transmission is most often autosomal dominant with incomplete penetrance and variable expressivity, whereas recessive forms, such as Naxos disease and Carvajal syndrome, associate arrhythmogenic cardiomyopathy with cutaneous or hair abnormalities. Diagnosis is complex because in the early phases echocardiography may show little abnormality, the patient may have only ventricular ectopy or electrocardiographic changes, and sudden death may precede the appearance of evident right ventricular dilatation.
The most typical cause of arrhythmogenic right ventricular cardiomyopathy is genetic. In most identifiable familial cases, pathogenic variants involve genes encoding desmosomal proteins, the intercellular adhesion structure that mechanically connects cardiomyocytes and contributes to tissue stability during contraction. The genes most frequently involved are PKP2, DSG2, DSC2, DSP, and JUP, which encode plakophilin-2, desmoglein-2, desmocollin-2, desmoplakin, and plakoglobin, respectively. Variants in TMEM43, DES, PLN, FLNC, LMNA, CDH2, and other genes may produce overlapping arrhythmogenic phenotypes, with predominant right-sided, left-sided, or biventricular involvement. The presence of a pathogenic variant alone is not enough to predict a uniform course, because penetrance, age at onset, and arrhythmic risk depend on genotype, sex, physical exercise, genetic modifiers, and the structural disease burden.
The desmosome has an essential function in the heart because cardiomyocytes undergo millions of cycles of stretching and shortening. When desmosomal proteins are altered, mechanical adhesion between cells becomes vulnerable, especially in regions exposed to greater wall stress. Detachment or fragility of intercellular contacts promotes cell death, reparative inflammation, and replacement by fibrous and fatty tissue. This replacement is not a simple fat deposit, but the result of a pathological process in which contractile myocardium is progressively replaced by noncontractile tissue that is electrically heterogeneous. The right ventricle is particularly vulnerable because it has a thin wall, complex geometry, and is highly affected by hemodynamic stress during intense exercise.
Pathogenesis is not exclusively mechanical. Desmosomal proteins interact with ion channels, gap junctions, the cytoskeleton, and intracellular signaling pathways. Loss of desmosomal function may alter connexin-43 localization, reducing electrical coupling between cardiomyocytes and creating conduction slowing. Plakoglobin may translocate from the desmosome to the nucleus and interfere with the Wnt/beta-catenin pathway, favoring adipogenic and fibrogenic programs. Mechanical stress, inflammation, apoptosis, and cell necrosis contribute to damage progression. The result is tissue in which viable areas, fibrosis, and adiposis alternate irregularly, generating electrical heterogeneity, slow conduction, and predisposition to re-entry circuits.
Definite genetic causes must be distinguished from factors that increase the likelihood of clinical expression. Intense and prolonged physical exercise, especially endurance exercise, is the most important environmental modifier. In carriers of desmosomal variants, high-load sports activity increases wall stress, right ventricular stretch, adrenergic tone, and mechanical demand on intercellular junctions, anticipating onset, increasing penetrance, accelerating remodeling, and increasing arrhythmic risk. Exercise-induced or exercise-favored arrhythmogenic phenotypes also exist in the absence of an identified desmosomal variant, but caution is required in these cases: not every right ventricular dilatation in an athlete is ARVC, and not every exertional arrhythmia indicates an inherited cardiomyopathy.
Clinical risk factors include family history of arrhythmogenic cardiomyopathy, sudden death at a young age, unexplained syncope, ventricular tachycardia, frequent ventricular ectopy, repolarization abnormalities in the right precordial leads, history of intense sports activity, male sex, carriage of multiple variants, variants in genes associated with higher risk, and left ventricular involvement. Family history may be subtle because penetrance is incomplete: a carrier parent may have only minimal electrocardiographic abnormalities, whereas a child develops ventricular tachycardia or sudden death. For this reason, the genealogy must look not only for already known diagnoses, but also for unexplained accidents, syncope, drownings, deaths during sports, pacemakers, defibrillators, and early heart failure.
Structural damage often follows a regional distribution. In the classic model, the first areas involved are the right ventricular outflow tract, the inferior region, and the apex, once described as the triangle of dysplasia. Fibrofatty replacement may determine wall thinning, dyskinesia, akinesia, localized aneurysms, and progressive right ventricular dilatation. However, the disease does not necessarily remain confined to the right ventricle. Left ventricular involvement may be early, late, or dominant, especially in some DSP, FLNC, PLN, LMNA, and desmin variants. When the left ventricle is involved, the picture may mimic myocarditis, arrhythmic dilated cardiomyopathy, or nondilated left ventricular cardiomyopathy, with subepicardial or mid-wall fibrosis and arrhythmias disproportionate to systolic function.
Arrhythmic pathophysiology is central and may precede pump dysfunction. In the early phases, global ventricular structure may be almost normal, but microscopic disorganization, loss of electrical coupling, and small areas of fibrosis already create an arrhythmogenic substrate. Ventricular ectopic beats may originate from the right ventricle and show left bundle branch block morphology, often with superior axis when the origin is inferior or subtricuspid. Sustained ventricular tachycardia may be monomorphic due to scar-related re-entry or may degenerate into ventricular fibrillation. Exercise increases adrenergic tone, heart rate, wall load, and electrical dispersion, explaining why many events occur during or shortly after intense activity.
Mechanical progression leads to right ventricular dilatation and dysfunction. When the free wall loses cardiomyocytes and is replaced by fibrofatty tissue, contraction becomes regionally and globally inefficient. Dilatation of the tricuspid annulus may cause functional tricuspid regurgitation; increased systemic venous pressures produce edema, jugular venous distension, hepatomegaly, and ascites. If the left ventricle becomes involved, reduced left ventricular ejection fraction, pulmonary congestion, and biventricular heart failure may appear. However, compared with classic dilated cardiomyopathy, arrhythmic risk may be high even when systolic dysfunction is only mild or moderate.
The inflammatory phase deserves attention because it may mimic acute myocarditis. Some patients, especially those with DSP variants, may present with chest pain, elevated troponin, myocardial edema on cardiac magnetic resonance, and a subepicardial enhancement pattern, with normal coronary arteries. These episodes may be interpreted as recurrent viral myocarditis, but may actually represent inflammatory expressions of genetic arrhythmogenic cardiomyopathy. The distinction is crucial because it changes follow-up, sports restriction, family screening, and arrhythmic risk stratification.
Recessive forms show how important the desmosome is outside the heart as well. In Naxos disease, linked to JUP variants, arrhythmogenic cardiomyopathy is associated with palmoplantar keratoderma and woolly hair. In Carvajal syndrome, often linked to DSP variants, involvement may be more markedly left-sided and associated with skin and hair signs. These phenotypes demonstrate that the heart, skin, and hair follicle share similar mechanical adhesion structures, and that extracardiac manifestations may guide early diagnosis.
The final result is a disease in which risk does not depend on a single parameter. Ventricular arrhythmias, scar extent, right ventricular dysfunction, left-sided involvement, family history, syncope, genotype, sex, physical activity, and ectopic burden all contribute to prognosis. The logical sequence is therefore clear: a genetic or structural vulnerability of intercellular junctions makes the myocardium fragile; mechanical stress and pathological cellular signals favor cardiomyocyte death and fibrofatty repair; the heterogeneous scar generates arrhythmias; progressive muscle loss produces ventricular dysfunction and heart failure. Arrhythmia is not an accessory feature of the disease, but one of its earliest and most dangerous biological manifestations.
Arrhythmogenic right ventricular cardiomyopathy may remain silent for years or manifest suddenly with ventricular arrhythmias. History taking must begin from the reason for evaluation: palpitations, syncope, presyncope, chest pain, dyspnea, family history, electrocardiographic abnormalities, ventricular ectopy on Holter monitoring, sports eligibility assessment, or resuscitated cardiac arrest. The disease should not be searched for only in patients with heart failure, because often the initial problem is electrical and the ventricle may still appear only minimally altered on basic imaging.
Palpitations are a frequent manifestation. The patient may report missed beats, thumps in the chest, rapid heartbeat, sudden episodes of regular tachycardia, or a sensation of the heart accelerating during exertion, stress, or recovery. Ventricular ectopic beats may be isolated, occur in couplets, appear in runs, or organize into nonsustained ventricular tachycardia. When ventricular tachycardia is sustained, symptoms depend on rate, duration, and ventricular function: palpitations, dizziness, dyspnea, chest pain, sweating, hypotension, or syncope. In some cases, the first manifestation is ventricular fibrillation or cardiac arrest.
Syncope is a symptom of major prognostic importance. A sudden loss of consciousness, without prodromes, during exercise, intense emotion, or in the supine position must be considered potentially arrhythmic until proven otherwise. Presyncope also deserves careful monitoring, especially when associated with palpitations. In young people and athletes, syncope is sometimes interpreted as vasovagal, but the presence of family history, ventricular ectopy, T-wave inversion in the right precordial leads, exercise-induced arrhythmias, or right ventricular abnormalities must immediately change the level of suspicion.
Dyspnea and reduced exercise tolerance appear when ventricular dysfunction becomes hemodynamically relevant or when frequent arrhythmias reduce efficiency and output. In phases with predominant right-sided involvement, the patient may describe fatigue, reduced performance, ankle swelling, abdominal heaviness, painful hepatomegaly, ascites, or weight gain from fluid retention. When the left ventricle is involved, dyspnea due to pulmonary congestion, orthopnea, and symptoms more similar to heart failure with reduced ejection fraction may appear. This clinical variability reflects the distribution of damage, not the presence of different diseases.
Chest pain is not the dominant symptom of the classic form, but it may be present, especially in phenotypes with an inflammatory component or left ventricular involvement. Episodes of pain with elevated troponin and normal coronary arteries may be mistaken for isolated myocarditis. If these episodes are recurrent, if ventricular arrhythmias coexist, if magnetic resonance imaging shows subepicardial or mid-wall enhancement, or if there is a family history, the possibility of arrhythmogenic cardiomyopathy must be explicitly considered. This is particularly important in carriers of DSP variants, in whom the phenotype may be more left-sided and myocarditis-like.
The sports history must be collected precisely. It is not enough to ask whether the patient practices sports; it is necessary to document the type of activity, years of practice, weekly hours, intensity, competition, endurance activity, episodes of symptoms during exercise, use of supplements or stimulants, and recent changes in performance. Intense physical activity is relevant both as a trigger for arrhythmic events and as an accelerator of penetrance in genetic carriers. A young athlete with ventricular ectopy of suspicious morphology, syncope, or repolarization abnormalities must not be reassured simply because they are well trained.
Family history is an essential part of the visit. At least three generations must be reconstructed, looking for sudden death before the age of 35 to 40 years, cardiac arrest, ventricular tachycardias, defibrillator implantation, cardiomyopathy, heart failure, transplantation, unexplained syncope, unclear road accidents, drownings, poorly defined epilepsy, deaths during sports, and diagnoses of recurrent myocarditis. Cutaneous or hair signs suggestive of syndromic forms, such as woolly hair or palmoplantar keratoderma, must also be sought. Since penetrance is incomplete, the absence of a formal diagnosis in relatives does not exclude familial disease.
On physical examination, many patients, especially in the early phases, have no evident signs. Blood pressure may be normal, cardiac auscultation may be silent, and signs of heart failure are not necessarily present. This apparent normality is one of the reasons for diagnostic difficulty. In patients with right ventricular dysfunction, jugular venous distension, dependent edema, hepatomegaly, ascites, and a murmur of functional tricuspid regurgitation may appear. In patients with left-sided involvement, pulmonary crackles, a third heart sound, signs of low output, and pulmonary congestion may appear.
Cardiac examination may reveal an irregular rhythm due to frequent ectopy, pauses, or episodes of tachycardia. A tricuspid murmur increases with inspiration and suggests annular dilatation or advanced right-sided dysfunction. The absence of murmurs is not reassuring. General examination must assess cutaneous, muscular, and neurological signs, because some arrhythmogenic cardiomyopathies overlap with dystrophies, desminopathies, laminopathies, or cardiocutaneous syndromes. Muscle weakness, contractures, skin abnormalities, woolly hair, keratoderma, neuropathy, or a history of myopathy must orient investigations beyond the heart alone.
In children and adolescents, presentation may be even more difficult. The disease may be absent on imaging but already present genetically, or may manifest with electrocardiographic abnormalities, ectopy, syncope, or sudden death. Surveillance of minor relatives must be adapted to the familial genetic variant, the age of onset in the family, the level of sports activity, and initial findings. In recessive cardiocutaneous phenotypes, dermatological manifestations may precede cardiac ones and allow early cardiological surveillance.
The realistic clinical sequence is therefore different from that of many mechanical cardiomyopathies. Suspicion often arises from an electrical event, an electrocardiographic finding, or family history; physical examination may be normal; diagnosis requires demonstration of a coherent pattern among arrhythmias, imaging, genetics, family history, and, rarely, histology. For this reason, the visit must not end with reassurance based only on the absence of heart failure, but with arrhythmic risk assessment and evaluation of the need for further investigations.
The diagnosis of arrhythmogenic right ventricular cardiomyopathy is multiparametric. No single test is sufficient in all cases, because the disease may initially be electrical, then structural, then biventricular or left-sided. The diagnostic pathway must integrate electrocardiography, rhythm monitoring, echocardiography, cardiac magnetic resonance, family history, genetic testing, and, in selected cases, endomyocardial biopsy or electrophysiological study. Diagnosis must also distinguish true ARVC from physiological athlete remodeling, myocarditis, sarcoidosis, tachycardiomyopathy, congenital heart disease, and other causes of right ventricular dilatation or arrhythmias.
The 12-lead electrocardiogram (ECG) is a first-level test. Suggestive findings include T-wave inversion in leads V1-V3 or beyond, epsilon waves in the right precordial leads, terminal activation delay of the QRS complex in the right precordial leads, incomplete or complete right bundle branch block, prolongation of the terminal portion of the QRS, ventricular ectopic beats with left bundle branch block morphology, and repolarization abnormalities not explained by other causes. Epsilon waves are specific but not very sensitive; their absence does not exclude the disease. T-wave inversion in the right precordial leads is more significant after puberty, because in children it may be a normal finding.
Holter monitoring and prolonged monitoring are fundamental. The finding of more than 500 ventricular ectopic beats in 24 hours, runs of nonsustained ventricular tachycardia, or sustained ventricular tachycardia with left bundle branch block morphology points toward a right ventricular origin. The axis of tachycardia helps localize the site of origin and has value in diagnostic criteria. In patients with intermittent symptoms, 24-hour Holter monitoring may not be enough; prolonged external recorders or implantable loop recorders may be used in selected cases. Monitoring is also useful during follow-up, because an increase in arrhythmic burden may precede structural progression.
Echocardiography assesses right ventricular size, function, and regional motion. It must look for right ventricular outflow tract dilatation, reduced fractional area change, akinesia, dyskinesia, regional aneurysms, global dilatation, functional tricuspid regurgitation, and left ventricular involvement. The examination is technically difficult because the right ventricle has complex geometry and a thin wall; for this reason, a normal echocardiogram does not exclude ARVC in the early phases. Echocardiography remains important for family screening, serial follow-up, hemodynamic assessment, and comparison with magnetic resonance imaging.
Cardiac magnetic resonance (CMR) is the most important imaging test for characterizing the right ventricle and left ventricular involvement. It allows measurement of right ventricular volumes and ejection fraction, identification of regional kinetic abnormalities, aneurysms, dilatation, wall thinning, and fibrosis. Late gadolinium enhancement (LGE) is particularly useful for recognizing left ventricular scar and biventricular or left-dominant phenotypes. CMR must be interpreted by experienced operators, because isolated epicardial or intramyocardial fat is not sufficient to diagnose ARVC, and the athlete may have right ventricular dilatation without disease.
The 2010 Revised Task Force Criteria are official diagnostic criteria that have historically been central for the predominantly right-sided form. They classify major and minor findings into different categories and allow a definite, borderline, or possible diagnosis. In summary, definite diagnosis requires two major criteria, or one major and two minor criteria, or four minor criteria from different categories; borderline diagnosis requires one major and one minor criterion, or three minor criteria from different categories; possible diagnosis requires one major criterion, or two minor criteria from different categories. The evaluated categories are the following:
The 2020 Padua criteria expanded the diagnostic reasoning because they more explicitly include right-dominant, biventricular, and left-dominant phenotypes, giving greater weight to tissue characterization by CMR and to the presence of pathogenic genetic variants. This evolution is important because the 2010 criteria were highly useful for the classic right-sided form, but less sensitive for forms with early or dominant left-sided involvement. In practice, when a left-sided arrhythmogenic phenotype is suspected, diagnosis requires particular caution: the presence of subepicardial or mid-wall LGE, ventricular arrhythmias, and a pathogenic variant must be distinguished from myocarditis, dilated cardiomyopathy, sarcoidosis, and other nonischemic cardiomyopathies.
Genetic testing has an important role, but must be interpreted rigorously. It is indicated in patients with a definite or suspected clinical diagnosis, familial cases, young patients with suggestive ventricular arrhythmias, biventricular or left-sided phenotypes, and when the result may guide screening of relatives. It must be preceded and followed by genetic counseling. A pathogenic variant in a coherent gene supports the diagnosis and allows cascade testing in relatives; a variant of uncertain significance must not be used as proof of disease; a negative test does not exclude ARVC if the clinical phenotype is convincing. Genetic panels must prioritize genes with a robust gene-disease relationship, because indiscriminate inclusion of weak genes increases the risk of incorrect interpretations.
Endomyocardial biopsy is not necessary in most patients, but may be useful when the diagnosis remains uncertain or when ARVC must be distinguished from sarcoidosis, myocarditis, infiltrative diseases, or tumors. The main limitation is the regional and often epicardial distribution of damage: an endocardial sample from the septum may fail to capture the involved free wall and reduce sensitivity. Biopsy must be performed in expert centers and interpreted with histology, immunohistochemistry, and, when indicated, assessment for inflammation or infectious agents.
Electrophysiological study may help in selected cases, especially to document inducibility of tachycardias, define arrhythmic mechanisms, plan ablation, or evaluate patients with syncope and discordant data. However, it is not a universal diagnostic tool nor a substitute for clinical stratification. Inducibility of ventricular tachycardia must be interpreted together with clinical history, spontaneous arrhythmias, ventricular function, CMR, genotype, and family history. In some patients, arrhythmia originates from epicardial substrates, making more complex ablation strategies necessary.
Blood tests do not diagnose ARVC, but help exclude alternative diagnoses or aggravating factors. Troponin and C-reactive protein may be useful if an inflammatory or myocarditis-like component is suspected; electrolytes, thyroid function, renal function, targeted toxicology, and inflammatory markers help in the evaluation of arrhythmias. If the picture suggests sarcoidosis, thoracic imaging, magnetic resonance, positron emission tomography (PET), and systemic assessments are performed. If congenital heart disease of the right ventricle is suspected, such as Ebstein anomaly or shunt, imaging must be adapted.
The differential diagnosis with athlete’s heart is one of the most delicate. Endurance sports activity may determine right ventricular dilatation, increased volumes, and occasional arrhythmias, but generally preserves function, lacks pathological regional abnormalities, lacks suggestive LGE, lacks family history, and shows reduction of findings after detraining. By contrast, ARVC tends to associate complex ventricular arrhythmias, ECG abnormalities, regional dyskinesias, fibrosis, family history, or positive genotype. The distinction must be entrusted to expert centers, because an error may lead either to unnecessary sports exclusion or to failure to prevent potentially fatal events.
The differential diagnosis includes myocarditis, cardiac sarcoidosis, dilated cardiomyopathy with arrhythmic phenotype, tachycardiomyopathy, idiopathic right ventricular outflow tract ectopy, congenital heart disease, pulmonary hypertension, chronic pulmonary embolism, Uhl disease, tricuspid valve abnormalities, and arrhythmogenic left ventricular phenotypes. Idiopathic outflow tract ectopy is usually benign, monomorphic, and occurs in the absence of structural and familial abnormalities; ventricular tachycardia due to ARVC, instead, is located within a pathological substrate and requires prognostic assessment. The final diagnosis must therefore describe phenotype, extent, genotype, arrhythmic risk, and family implications.
The treatment of arrhythmogenic right ventricular cardiomyopathy has the main goal of preventing sudden cardiac death and reducing arrhythmic burden, without neglecting heart failure, structural progression, and family screening. Therapy does not aim to “cure” fibrofatty replacement that is already present, but to reduce events, limit triggers, control arrhythmias, treat ventricular dysfunction, and identify at-risk relatives early. Management must be individualized because an asymptomatic carrier, an athlete with sustained ventricular tachycardia, a patient with left ventricular involvement, and a subject with advanced right-sided heart failure have different needs.
Restriction from intense physical exercise is a therapeutic cornerstone. In patients with definite ARVC and in carriers of at-risk pathogenic variants, competitive sports and high-intensity endurance activity must be avoided, because they increase penetrance, progression, and arrhythmic risk. The goal is not to impose absolute sedentary behavior, but to replace intense exercise with low-intensity activity, personalized and discussed with the cardiologist. This point must be explained clearly to the patient, especially if young or athletic, because reducing sports load is one of the most important and most difficult interventions to accept.
Beta-blockers are often used to reduce adrenergic tone, heart rate, ectopy, and exercise-induced arrhythmias, especially in patients with documented arrhythmias or increased risk. They do not eliminate the arrhythmic substrate and do not replace the defibrillator when indicated, but may reduce triggers and symptoms. Antiarrhythmic medications may be necessary in patients with recurrent tachycardias, defibrillator shocks, or high arrhythmic burden. Sotalol and amiodarone are among the most used options in selected settings, but require assessment of efficacy, side effects, ventricular function, QT interval, age, and comorbidities. The choice must be specialist-led, because pharmacological arrhythmia treatment in ARVC is often a containment strategy, not definitive protection from sudden death.
The implantable cardioverter-defibrillator (ICD) is the most effective treatment for interrupting potentially fatal ventricular tachycardia or ventricular fibrillation. It is indicated for secondary prevention after cardiac arrest, ventricular fibrillation, or hemodynamically relevant sustained ventricular tachycardia not attributable to a reversible cause. In primary prevention, the decision integrates suspected arrhythmic syncope, nonsustained ventricular tachycardia, ectopic burden, right or left ventricular dysfunction, disease extent, genotype, sex, age, family history, and results from risk models. The ICD protects from lethal arrhythmia, but does not prevent cardiomyopathy progression and may involve inappropriate shocks, infections, lead complications, and psychological impact.
Risk stratification is dynamic. Patients with previous cardiac arrest or sustained ventricular tachycardia have high risk and require strong protection. In subjects without major events, clinical variables such as age, sex, syncope, nonsustained ventricular tachycardia, number of ventricular ectopic beats, T-wave inversion, right ventricular function, left ventricular function, and genotype are considered. Predictive models, such as those developed to estimate the 5-year risk of ventricular arrhythmias in patients with ARVC, can support decision-making, but do not replace clinical judgment, especially in left-sided phenotypes, nonclassic variants, and patients with incomplete data.
Catheter ablation has an important role in controlling recurrent ventricular tachycardias, but it must not be interpreted as a definitive cure for the disease. Ventricular tachycardia in ARVC often arises from subepicardial or intramural scars, and simple endocardial ablation may not be sufficient. In expert centers, endocardial, epicardial, or combined approaches may be used, guided by electroanatomical mapping and imaging. Ablation is particularly useful for reducing recurrences, ICD shocks, and arrhythmic burden, but the substrate may progress and generate new circuits over time.
Treatment of heart failure follows the hemodynamic phenotype. If right ventricular dysfunction predominates, management includes control of congestion with diuretics, attention to preload, treatment of functional tricuspid regurgitation when relevant, and assessment of arrhythmias that worsen function. If left ventricular dysfunction is present, the principles of heart failure with reduced ejection fraction are applied, using angiotensin receptor-neprilysin inhibitor (ARNI), angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta-blockers, mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter type 2 inhibitors (SGLT2i), and diuretics according to tolerance and indications. In advanced cases, heart transplantation or mechanical support may be considered.
Family management is part of treatment. In first-degree relatives, genetic counseling, ECG, Holter monitoring, echocardiography, cardiac magnetic resonance when appropriate, and targeted genetic testing if the familial variant is known are indicated. Genotype-positive and phenotype-negative subjects must be followed over time, because the disease may appear after years and penetrance increases with age and exercise. The frequency of follow-up depends on age, genotype, family history, level of physical activity, and initial findings. Family communication must be clear: a positive test does not always equal manifest disease, but requires surveillance and caution regarding intense activity.
Pregnancy requires individualized assessment. Many women with stable disease can complete pregnancy, but arrhythmias, ventricular function, antiarrhythmic therapy, ICD, history of heart failure, and genotype must be discussed before conception. During pregnancy, plasma volume, heart rate, and hemodynamic load increase; these factors may favor arrhythmias or worsening in vulnerable patients. Management must coordinate cardiology, obstetrics, anesthesia, and genetics, including discussion of hereditary risk.
Prognosis is heterogeneous. Many patients diagnosed early, protected by sports restriction, monitoring, and ICD when indicated, have long survival. Prognosis worsens in the presence of cardiac arrest, sustained ventricular tachycardia, arrhythmic syncope, left ventricular involvement, biventricular dysfunction, high ectopic burden, extensive LGE, high-risk genotypes, multiple variants, continued intense sports activity, and progressive heart failure. Sudden death can be significantly prevented when risk is recognized, but the disease remains chronic and requires ongoing follow-up.
Prognosis must not be communicated as an inevitable destiny. Natural history can be modified by early diagnosis, reduction of intense exercise, arrhythmic protection, control of tachycardias, heart failure management, and family screening. However, risk must not be trivialized: absence of symptoms does not equal absence of substrate, and normality of a single test does not exclude future progression. Modern ARVC management is therefore a medicine of active surveillance, in which prevention of the arrhythmic event matters as much as treatment of symptoms that have already appeared.
The most feared complication is sudden cardiac death. It may result from rapid ventricular tachycardia or ventricular fibrillation, often triggered by exercise, adrenergic tone, ectopy, or progression of the scar substrate. The risk is particularly relevant in young people and athletes, because the disease may still be only minimally evident structurally but already arrhythmogenic. Prevention requires early recognition, restriction from intense activity, risk stratification, and ICD when indicated. Cardiac arrest may be the first manifestation, which is why family history and screening of relatives have real preventive value.
Sustained ventricular tachycardias are a frequent complication in symptomatic patients. They may be monomorphic, related to scar-based re-entry circuits, or degenerate into more unstable arrhythmias. They cause palpitations, syncope, shock, hospitalizations, ICD interventions, and worsening quality of life. Recurrences are common because the substrate may be extensive, epicardial, and progressive. Antiarrhythmic medications and ablation reduce the burden, but do not eliminate the biological vulnerability of the myocardium.
ICD shocks are both a therapeutic and clinical complication. Appropriate shocks interrupt dangerous arrhythmias, but signal an electrically active disease. Inappropriate shocks may result from supraventricular tachycardias, oversensing, lead problems, or nonoptimized programming. Both may have a significant psychological impact, with anxiety, avoidance of physical activity, sleep disturbance, and reduced quality of life. Accurate programming, arrhythmia control, and device follow-up are therefore integral parts of care.
Progression toward right ventricular dysfunction produces right-sided heart failure. Loss of contractile myocardium, cavity dilatation, and functional tricuspid regurgitation increase systemic venous pressures. Jugular venous distension, dependent edema, congestive hepatomegaly, ascites, early satiety, and reduced exercise tolerance appear. Right-sided heart failure may be underestimated if attention is focused only on left ventricular function. In advanced cases, chronic congestion damages the liver, kidney, intestine, and nutritional status.
Left ventricular involvement is a complication and, in some patients, an early component of the disease. When it appears, it increases the risk of heart failure, ventricular arrhythmias, extensive LGE, and differential diagnosis with myocarditis or dilated cardiomyopathy. Left-sided dysfunction changes therapy because it introduces typical indications for heart failure with reduced ejection fraction and may influence the ICD decision. In DSP phenotypes and other left-sided forms, progression may be accompanied by inflammatory episodes and elevated troponin.
Supraventricular arrhythmias, including atrial fibrillation, may appear with atrial dilatation, heart failure, age, or atrial scar. They are not the most specific manifestation of the disease, but may worsen hemodynamics, symptoms, and thromboembolic risk. In patients with impaired ventricular function, rapid atrial fibrillation may precipitate heart failure or increase inappropriate ICD interventions. Management requires rhythm or rate control, anticoagulation when indicated, and review of device programming.
Thromboembolic events are less central than in other cardiomyopathies, but may occur in the presence of severe ventricular dysfunction, aneurysms, atrial fibrillation, marked dilatation, or advanced heart failure. Stasis in dysfunctional chambers may promote intracavitary thrombi; embolism may involve the cerebral or systemic circulation. Prevention is not automatic in all patients with ARVC, but depends on rhythm, ventricular function, presence of thrombi, and individual risk.
Incorrect diagnosis is an indirect but relevant complication. Mistaking ARVC for idiopathic ectopy may leave the patient exposed to intense sports and arrhythmic risk. Mistaking athlete’s heart for ARVC may instead produce sports exclusion, anxiety, unnecessary procedures, and inappropriate family screening. Confusing left-sided phenotypes with isolated myocarditis may prevent genetic counseling and protection of relatives. For this reason, diagnosis must rely on multiparametric criteria and not on a single suggestive finding.
Psychological and social complications are frequent. Diagnosis at a young age, suspension from competitive sports, ICD implantation, fear of shocks, familial risk, and implications for children and siblings may generate anxiety, depression, isolation, or family conflicts. The athlete may experience sports restriction as a loss of identity. Counseling must therefore be both clinical and psychological, with rational explanation of risk and safe alternatives for physical activity.
Family complications derive from the inherited nature of the disease. An unrecognized proband may have unsupervised carrier relatives. Conversely, a misinterpreted genetic variant may classify as diseased subjects who only have a variant of uncertain significance. Family management requires genetic counseling, targeted testing when the variant is pathogenic, serial controls, and cautious interpretation. Prevention of familial sudden death often depends on the quality of this pathway.
Complications of advanced treatments include device infections, lead dislodgement or fracture, inappropriate shocks, venous access complications, antiarrhythmic toxicity, recurrence after ablation, epicardial complications, bleeding, coronary injury, or post-procedural pericarditis. In patients with advanced heart failure, mechanical support and transplantation carry specific risks, but may be life-saving options. The presence of complications does not reduce the value of therapies when indicated; it requires correct selection, expert centers, and rigorous follow-up.
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