Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC, ARVD) (2023)

Cardiomyopathy / Arrhythmogenic Right Ventricular Dysplasia (ARVC, ARVD)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy that predominantly affects the right ventricle. CVDA is defined by the gradual loss of myocardial cells, which are replaced by adipose and fibrous tissue. This process begins at the epicardium and gradually moves to the endocardium. As fibro-fat replacement progresses, the ventricular wall thins and the ventricle begins to dilate. About 50% of cases have biventricular cardiomyopathy, with the disease being less pronounced in the left ventricle. Rarely is the condition confined to the left ventricle. Causes of ARVCventricular tachycardiaand sudden cardiac arrest; The disease is one of the most common causes of sudden cardiac arrest in adolescents and athletes (hypertrophic cardiomyopathyis the most common cause).

Genetic mutations in ARVC

At least 13 genes have been implicated in ARVC. Most of these are genes that encodeDesmosomal Protein. The desmosome is part of theDisc-Interleavemechanically and electrically connects the myocardial cells. Most mutations are inherited in an autosomal dominant manner, with variable penetrance and expressivity. There are recessive forms, but they are rare (Naxos disease, Carvajal syndrome). The prevalence of ARVC in Europe is between 0.02 and 0.05% (Corrado and others). ARVC is more malignant in males, the reason for this remains elusive.

Genetic mutations can be confirmed in about 60% of people with ARVC. Mutations in the desmosomal genePKP2is most common. Mutations in non-desmosomal genes are less common. The following genes are associated with ARVC:

• CTNNA3
• AGAIN
• DSC2
• DSG2
• DSP
• Jupp
• LMNA
• PKP2
• PLN
• RYR2
• TGFB3
• TMEM43
• TTN

Clinical features of ARVC

ARVC is typically occult (asymptomatic) in childhood and adolescence and becomes symptomatic between the second and fourth decades of life. Likewise, the right ventricle can appear functionally and morphologically normal in the first two decades of life in echocardiography and cardiac magnetic resonance imaging.

The most common initial presentation is palpitations or syncope. However, ARVC can cause ventricular tachycardia, which can degenerate into ventricular fibrillation at any age. Exercise or other activities that cause adrenergic stimulation increase the risk of syncope, ventricular arrhythmias, and sudden cardiac arrest.

ARVC can cause ventricular tachycardia, ventricular fibrillation, and sudden cardiac arrest at any age. Palpitations, syncope, or cardiac arrest—particularly during physical activity—in a young adult with T-wave inversions in V1–V4 or other ECG changes (see below) should raise suspicion of ARVC.

The gradual loss of the myocardium leads to ventricular dilatation andheart failure. Biventricular heart failure is less common.

ECG in ARVC

• T-wave inversionin leadership V1 to V4.
• then epsilon, a late depolarization/potential that occurs between the end of the QRS complex and the onset of the T-wave, in leads V1 and V2 (Figure 1).
• Terminal Activation Duration (TAD), defined as the interval between the nadir (lowest point) of the S-wave and the end of the depolarization, is prolonged (> 55 ms in V1-V2). See Figure 2.
• Epsilon wave and extended DAT strongly suggest ARVC.
• Low electrode voltage of the limbs.
• Patients with ARVC are commonpremature ventricular contractions (PVC)who can proceedmonomorphic ventricular tachycardia (VT).
• Ventricular tachycardia in ARVC has an LBBB morphology with negative T waves in V1 through V4.
• PVCs and ventricular tachycardia can be induced by any physical adrenergic stimulation, such as physical activity.

Echocardiography in ARVC

Echocardiography shows global dilatation of the right ventricle. The left ventricle and septum are usually spared. Regional wall motion abnormalities—ie, hypokinesia, dyskinesia, and kinesia—can also be seen. A ventricular aneurysm develops with pronounced fibro-fat replacement.

Because echocardiography is not sufficient to visualize the right ventricle, cardiac magnetic resonance (MR) is the imaging technique of choice. Delayed gadolinium enhancement can be used to estimate the extent of fibro-fat replacement.

Differential diagnoses for ARVC

• Idiopathic TVV-SVD (ventricular tachycardia originating from TVVD).
• Sarcoidosis.
• congenital heart defectwith right ventricular strain.

Diagnostic criteria for ARVC

The diagnosis is based on clinical data, ECG, genetic analysis and cardiac magnetic resonance imaging. Current criteria (supported by ESC, AHA, ACC) use major and minor criteria divided into 6 categories. Based on the findings, the likelihood of ARVC can be classified as possible, borderline, or definite:

• final ARVC: 2 majors or 1 major and 2 minors or 4 minors from different categories
• Borderline-ARVC: 1 major and 1 minor or 3 minors from different categories.
• Possible ARVC: 1 major or 2 minors from different categories

Table 1. Criteria for ARVC

The categories are numbered from 1 to 6.

• CATEGORY 1: Global or regional dysfunction and structural change†
  • Ökokardiographie 2D
    • main criteria: Regional RV akinesia, dyskinesia, or aneurysm and any of the following (end diastole): PLAX SVOT ≥ 32 mm (≥ 19 mm per square meter when corrected for body surface area), PSAX RVOT ≥ 36 mm (≥ 21 mm per square meter when corrected for body surface area). corrected) or a fractional area change of ≤33%.
    • Minor criteria: Regional RV akinesia or dyskinesia and one of the following (end diastole): PLAX SVOT 29 to <32 mm (16 to <19 mm per square meter with body surface area correction), PSAX RVOT 32 to <36 mm (18 to <21 mm per square meter when correcting the body surface) or 34 to 40% change in area percentage.
  • MRI (Magnetic Resonance Imaging)
    • Key criteria: regional RV akinesia or dyskinesia or dyssynchronous RV contraction and one of the following: RV end-diastolic volume to body surface area ratio ≥ 110 mL per square meter (male patients) or ≥ 100 mL per square meter (female patients). patients) or RV ejection fraction ≤ 40%.
    • secondary criteria: Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and any of the following: RV end-diastolic volume to body surface area ratio 100 to < 110 mL per square meter (male patients) or 90 to < 100 mL per square meter (female patients). patients) or RV ejection fraction 41 to 45%.
  • right ventricular angiography
    • main criteria: RV regional Akinesia, Dyskinesia or Aneurysm.
• CATEGORY 2: Tissue Characterization
  • main criteria: <60% residual myocytes on morphometric analysis (or <50% if estimated) and fibrous replacement of RV free-wall myocardium, with or without adipose tissue replacement, in at least one endomyocardial biopsy specimen.
  • secondary criteria: 60 to 75% residual myocytes by morphometric analysis (or 50 to 65% if estimated) and fibrous replacement of RV free-wall myocardium, with or without adipose tissue replacement, in at least one endomyocardial biopsy specimen.
• CATEGORY 3: Repolarization abnormalities
  • main criteria: Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in patients older than 14 years (without complete right bundle branch block, QRS ≥ 120 ms).
  • secondary criteria: Inverted T waves in leads V1 and V2 in patients older than 14 years (without complete right bundle branch block) or in V4, V5, or V6; inverted T-waves in leads V1, V2, V3, and V4 in patients older than 14 years (in the presence of complete right bundle branch block).
• CATEGORY 4: Depolarization and conduction disturbances
  • main criteria: Epsilon wave (reproducible low-amplitude signals from the end of the QRS complex to the beginning of the T-wave) in the right precordial leads (V1, V2 and V3).
  • secondary criteria: ECG late potentials of the mean signal in at least one of the three parameters without QRS complex duration of ≥110 ms in the standard ECG; Duration of filtered QRS complex ≥ 114 ms; Terminal QRS complex duration < 40 μV (low amplitude signal duration), ≥ 38 ms; Terminal mean square voltage 40 ms, ≤20 μV; Duration of terminal QRS complex activation, ≥55 ms, measured from the nadir of the S wave to the end of the QRS complex, including R', in V1, V2, or V3, without complete right bundle branch block.
• CATEGORY 5: Arrhythmias
  • main criteria: Sustained or non-sustained ventricular tachycardia with left bundle branch block and upper axis pattern (negative or indeterminate QRS complex in leads II, III and aVF and positive QRS complex in lead aVL).
  • secondary criteria: Nonsustained or sustained ventricular tachycardia of RV outflow configuration with left bundle branch block and lower axis pattern (positive QRS complex in leads II, III and aVF and negative QRS complex in lead aVL) or unknown axis or > 500 ventricular premature beats per 24 hours (with Holter monitoring).
• CATEGORY 6: Family history
  • main criteria: ARVC confirmed in a first-degree relative meeting current task force criteria, ARVC pathologically confirmed at autopsy or surgery in a first-degree relative, or identification of a pathogenic mutation thought to be associated or likely to be associated with ARVC in the patient examined classified‡ .
  • secondary criteria: History of ARVC in a first-degree relative in whom it is not possible or practical to determine if current Task Force criteria are met, sudden premature death (< 35 years) due to suspected ARVC in a first-degree relative, or ARVC pathologic or confirmed by current task force criteria in a second-degree relative.

Table adapted fromMark is aEU.

The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is considered definitive when the patient meets two major criteria, one major and two minor, or four minor criteria from different categories; the diagnosis is considered borderline if the patient meets one major and one minor criterion or three minor criteria from different categories, and the diagnosis is considered possible if the patient meets one major or two minor criteria from different categories. ECG denotes electrocardiogram, PLAX long axis view, parasternal view, PSAX parasternal short axis view, RV right ventricle and RV outflow tract VSVOT.

†Hypokinesia is not included in this or subsequent definitions of regional RV motility abnormalities for the proposed modified criteria.
‡A pathogenic mutation is an ARVC-associated DNA change that alters or is expected to alter the encoded protein that is not observed or rare in a large non-ARVC control population, and alters or is expected to alter the structure or function of the protein or has been shown to be associated with the disease phenotype in a conclusive pedigree (i.e., a pedigree that provides conclusive evidence of Mendelian inheritance of the disease phenotype).

ARVC treatment

ARVC treatment focuses primarily on preventing sudden cardiac arrest. There are no randomized controlled trials supporting the use of antiarrhythmic drugs. Beta-blockers do not have antiarrhythmic effects, but are still prescribed for most patients with ARVC because they can reduce the effect of adrenergic stimulation on the heart. An ICD should be considered in patients with syncope, left ventricular dysfunction, or risk factors for sudden cardiac arrest. Right heart failure is treated as HFREF (Reduced Ejection Fraction Heart Failure).