Arrhythmogenic Right Ventricular Dysplasia

Heiko Schmitt, M.D., PH.D.

Basic Information

Definition

Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy characterized by replacement of the normal myocardium with fibrofatty tissue, mainly of the right ventricle but also occasionally with involvement of the left ventricle. It is defined clinically by palpitations and syncope and potentially life-threatening ventricular arrhythmias.

Synonyms

Arrhythmogenic right ventricular cardiomyopathy
ARVC

ICD-10CM CODES
I42.8	Arrhythmogenic ventricular dysplasia

Epidemiology & Demographics

Prevalence

1:2000-5000 persons. It is one of the leading causes of arrhythmic cardiac arrest in young people and athletes

Predominant Sex and Age

Mean age, 31 yr (range, 12-50 yr), predominantly male

Risk Factors

Family history of ARVD (present in nearly 50% of affected patients)

Genetics

•

Autosomal dominant (most common) with variable penetrance and polymorphic phenotypic expression.
•

Autosomal recessive (rarely, e.g., Naxos disease).
•

Several different gene mutations in desmosomal proteins.
•

Gene mutations can be identified in 50% of affected individuals.

Physical Findings & Clinical Presentation

•

ARVD can present with palpitations, syncope, and chest discomfort and less commonly sudden cardiac arrest and signs of right ventricular failure such as dyspnea, edema, and fatigue. Patients may be clinically asymptomatic for many years.
•

Cardiac arrest after physical exertion may be the initial presentation.
•

Physical examination will be normal in most patients. Widely split S2 is an important diagnostic clue.

Etiology

ARVD is characterized by progressive replacement of mainly the right ventricular myocardium with fibrofatty tissue after apoptotic myocardial cell death caused by mutations of desmosomal protein.

Diagnosis

•

A major criteria equals 2 points; a minor criteria equals 1 point. The diagnosis of ARVD is considered definite if the patient has 4 points and probable with 3 points. See Table 1 for diagnostic criteria.

TABLE1 Global or Regional Dysfunction and Structural AlterationsFrom Marcus IM: Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia proposed modification of the Task Force criteria. Circulation 121:1533-1541, 2010.

Major
2D echo criteria
Regional RV akinesia, dyskinesia, or aneurysm and one of the following measured at end diastole
PLAX RVOT ≥32 mm or
PSAX RVOT ≥36
Fractional area change ≤33%
MRI criteria
Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and one of the following
Ratio of RV end-diastolic volume to BSA >100, <110 ml/m² (male) or >100 ml/m²
RV ejection fraction >40% ≤45%
RV angiography criteria
Regional RV akinesia, dyskinesia, or aneurysm
Minor
2D echo criteria
Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and one of the following measured at end diastole
PLAX RVOT ≥29 <32 mm or
PSAX RVOT ≥32 <36
Fractional area change >33% ≤40%
MRI criteria
Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and one of the following
Ratio of RV end-diastolic volume to BSA ≥110 ml/m² (male) or _≥100 ml/m²
RV ejection fraction ≤40%
Tissue characterization of wall
Major
Residual myocytes <60% by morphometric analysis (or <50% if estimated) with fibrous replacement of the RV free wall myocardium in >1 sample, with or without fatty replacement of tissue on endomyocardial biopsy
Minor
Residual myocytes 60%-75% by morphometric analysis (or 50%-65% if estimated), with fibrous replacement of the RV free wall myocardium in >1 sample with or without fatty replacement of tissue on endomyocardial biopsy
Repolarization abnormalities
Major
Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in individuals >14 y of age (in the absence of complete RBBB QRS ≥120 ms)
Minor
Inverted T waves in V1 and V2 in individuals >14 y of age (in the absence of complete RBBB) or in V4, V5, and V6
Inverted T waves in leads V1, V2, V3, and V4 in individuals >14 y of age in the presence of a complete RBBB
Depolarization or conduction abnormalities
Major
Epsilon wave (reproducible low-amplitude signals between end of QRS complex to onset of T wave) in the right precordial leads (V1-V3)
Minor
Late potentials by SAECG in ≥1 of 3 parameters in the absence of a QRSd of ≥110 ms on standard ECG
Filtered QRS ≥114 ms
Duration of terminal QRS <40 mV ≥38 ms
Root-mean-square voltage of terminal 40 ms ≤20 μV
Terminal activation duration ≥55 ms measured from the nadir of the end of the QRS, including R’, in V1, V2, or V3 in absence of complete RBBB
Arrhythmias
Major
Nonsustained or sustained VT of LBBB morph with superior axis
Minor
Nonsustained or sustained VT of RVOT configuration, LBBB morph with inferior axis or of unknown axis
>500 PVCs per 24 h (Holter)
Family history
Major
ARVD/C in first-degree relative who meets Task Force criteria
ARVD/C confirmed pathologically at autopsy or surgery in first-degree relative
Identification of pathogenic mutation categorized as associated or probably associated with ARVD/C in the patient under evaluation
Minor
History of ARVD/C in first-degree relative in whom it is not possible to determine whether the family member meets Task Force criteria
Premature sudden death (<35 y of age) caused by suspected ARVD/C in a first-degree relative
ARVD/C confirmed pathologically or by current Task Force criteria in second-degree relative
A major criteria equals 2 points, a minor criteria 1 point. The diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) is considered definite if the patient has 4 points and probable with 3 points. BSA, body surface area; MRI, magnetic resonance imaging; RBBB, right bundle branch block; RV, right ventricle; RVOT, right ventricular outflow tract; 2D, two dimensional; VT, ventricular tachycardia.

Differential Diagnosis

•

Cardiomyopathy with involvement of the right ventricle
•

Uhl’s anomaly: rare anomaly that presents mainly in childhood with signs and symptoms of right heart failure and characterized by a paper-thin right ventricle resulting from death of the myocytes throughout the right ventricle
•

Idiopathic RV tachycardia
•

Sarcoidosis
•

Right ventricular infarction

Workup

•

Initial workup includes history with focus on sudden death in the family, resting ECG, 24-Holter ECG, signal-averaged ECG, and imaging studies with echocardiography and MRI.
•

ECG will have diagnostic findings in 50% to 90% of patients with ARVD, including T-wave inversions in anterior precordial leads V₁-V₆, epsilon waves, and a QRS duration longer than 110 ms in V1 or >40 ms longer in V1 than v6. (Fig. 1).

FIG.1

Arrhythmogenic right ventricular cardiomyopathy—Epsilon wave.

This 12-lead ECG tracing with lead Vfn11 rhythm strip (A) shows sinus rhythm with T-wave inversion over the right precordial leads. In addition, there is an epsilon wave (small deflection at the end of the QRS complex), evident in lead V¹ (B), which is characteristic of arrhythmogenic right ventricular cardiomyopathy.

From Olshansky B, Chung MK, Pogwizd SM, et al.: Arrhythmia essentials, ed 2, Philadelphia, 2017, Elsevier.
•

Ventricular tachycardia (VT) with left bundle branch block pattern and frequent PVCs (>500 in 24 h) might be detected by 24-hr Holter monitoring.
•

An abnormal signal-averaged ECG is a minor diagnostic criteria.
•

Echocardiography will show right ventricular dilation with regional wall motion abnormalities, aneurysms, and depressed RV function that varies with the severity of the disease.
•

MRI (Fig. 2) is a noninvasive method to detect structural abnormalities (fibrofatty changes) and regional dysfunction. Cardiac MRI (CMR) is the most sensitive method to detect ARVD, but it has high false-positive rates. Cardiac CT angiogram (Fig. E3) will reveal thinning and aneurysmal dilation of the RV anterior wall and outflow tract.

FIG.2

Arrhythmogenic right ventricular cardiomyopathy. Spin-echo cardiovascular magnetic resonance without (A) and with (B), a fat-suppression prepulse. There is bright signal in the free wall of the right ventricle that suppresses with fat suppression (arrows).

From Sellke FW, del Nido PJ, Swanson SJ: Sabiston & Spencer surgery of the chest, ed 9, Philadelphia, 2016, Elsevier.

FIG.E3

Right ventricular aneurysm.

This cardiac computed tomography angiogram shows thinning and aneurysmal dilation of the RV anterior wall and outflow tract (arrows) in a patient with arrhythmogenic right ventricular dysplasia, cardiomyopathy, and ventricular tachycardia. Ao, Aorta; LV, left ventricle; PA, pulmonary artery.

Courtesy of Dr. Nasar Nallamothu, Prairie Cardiovascular Consultants, Springfield, Ill. From Issa Z et al: Clinical arrhythmology and electrophysiology, ed 2, Philadelphia, 2012, Saunders.

If the routine tests are not conclusive, endomyocardial biopsy and electrophysiologic testing can be considered. However, biopsies and radionuclide ventriculography are rarely performed in the U.S.

Treatment

No curative treatment is available. The treatment goal is focused on preventing sudden cardiac death, symptomatic treatment of right heart failure, and pharmacologic and invasive treatment of arrhythmias. Family members with a negative phenotype (either healthy gene carriers or those with an unknown genotype) do not need any specific treatment other than sports restriction; however, lifelong clinical assessment with the use of noninvasive tests at least every 2 years is warranted.¹

Nonpharmacologic Therapy

•

Avoidance of activity that may trigger ventricular tachycardia and may lead to disease progression.
•

ICD implantation needs to be considered in patients who have the definite diagnosis of ARVD. Patients with unexplained syncope, advanced disease, documented ventricular arrhythmias, or a family history of sudden cardiac death or who have been resuscitated from cardiac arrest are at high risk. A subcutaneous ICD might be an alternative option instead of transvenous implantation.
•

Radiofrequency catheter ablation is used in cases of refractory VT or frequent tachycardia after defibrillator placement.
•

Cardiac transplantation.
•

Fig. 4 describes a management algorithm for ARVD.

FIG.4

Arrhythmogenic right ventricular cardiomyopathy.

From Olshansky B, Chung MK, Pogwizd SM, et al.: Arrhythmia essentials, ed 2, Philadelphia, 2017, Elsevier.

Pharmacologic Treatment

•

Antiarrhythmic therapy with sotalol (first-line treatment) or amiodarone, often in combination with beta-blockers, is used for tachycardia suppression.

Referral

•

Early cardiology and electrophysiology referral
•

Consider referring for genetic counseling

Pearls & Considerations

Prevention

All first-degree relatives should be tested if ARVD is confirmed. Sports activity increases the risk of sudden cardiac death among adolescents and young adults with ARVC. The estimated overall mortality ranges from 0.08% to 3.6% per year.

Ferri – Arrhythmogenic Right Ventricular Dysplasia