Arrhythmogenic right ventricular dysplasia (ARVD) is an cardiomyopathy with transmission of autosomal dominant type with incomplete penetrance and variable expression associated with malignant ventricular arrhythmias and sudden death in young, apparently healthy people, characterized by structural and functional abnormalities of the right ventricular zone given by replacement of the myocardium with fatty and fibrous tissue. Genes involved (chromosome 14q23) are responsible for the synthesis of cell junction proteins from the disc insertion like plakoglobin, plakophilin, desmoglein, desmocollin and desmoplakin. Other embodiments of the disease are explained by mutations in the ryanodine receptor 2 or genes involved in the synthesis of TGF (transforming growth factor). These anatomical changes are found in the right ventricle, in the dysplasia triangle formed by sub-tricuspid area, right ventricular apex and infundibulum (respectively lower wall, apical and infundibular). There is also an autosomal recessive version associated with plantar and palmar keratosis, hair wool called Naxos disease (from the Naxos island where the first cases were found).
In the past 25 years, has been identified the genetic disease and its substrate, the risk of sudden death has been developed by the diagnostic criteria and therapeutic measures were taken. The first description of the disease actually belongs to Giovanni Maria Lancisi in 1736, which, in his book entitled “De Motu Cordis Et Aneurysmatibus ” reports a family with affection transmission over 4 generations and manifested by palpitations, heart failure, expansion and right ventricular aneurysm and sudden death. In 1995 this condition was included in the revised classification of the World Health Organization among cardiomyopathies. The overall prevalence is between 1/2500 and 1/5000; there are areas such as Padua and the island of Naxos where sudden death rate is between 5 and 10% in people under 65 years. After the hypertrophic cardiomyopathy is the first cause of sudden death in young, male / female ratio being 2.7:1.
The natural history of ARVD is in 4 stages:
Phase 1 – the subclinical structural abnormalities are hidden; cardiac arrest may be the first and last manifestation of the disease; is the first cause of sudden death in athletes (Venice, Italy) and the second leading cause of sudden death in young people;
Phase 2 – electrical instability when occurring ventricular arrhythmias: from the isolated ventricular extra-systoles to sustained ventricular tachycardia with morphology of type block of left bundle-branch and ventricular fibrillation; morphology and axis of ventricular tachycardia suggests its site (bottom-axis the ejection tract and the upper axis -lower wall);
Phase 3 – right ventricular failure;
Phase 4 – biventricular failure, mimicking dilated cardiomyopathy.
ARVD diagnosis is often difficult; it is based on criteria like major and minor structural, histological, electrocardiographic and genetic. It requires two major criteria, or one major and two minor, or four minor. The role of an essential diagnostic it has the electrocardiographic. ARVD is a condition that develops over time and is influenced by age (evolution is subclinical until puberty) and it seems by other environmental variables such as athletics. Therefore, it is difficult to develop a diagnostic criterion.
The differential diagnosis it is made with idiopathic tachycardia of right ventricular outflow tract (RVOT), myocarditis, dilated cardiomyopathy and sarcoidosis.
Diagnostic criteria for ARVD
Global dysfunction and / or regional and structural abnormalities
1. Severe dilatation and reduction of the right ventricle ejection fraction with normal or only mildly impaired left ventricular;
2. Aneurysm of the right ventricle;
3. Severe segmental dilatation of the right ventricle;
1. Overall moderate in the right ventricle dilatation and / or ejection fraction decreased by keeping a normal function of the left ventricle;
2. Segmental moderate dilatation of the right ventricle;
3. Regional hypokinesia of the right ventricle.
1. Fibro-fatty meshes at the myocardial level proven by endomyocardial biopsy.
CRITERIA FOR ELECTRO-CARDIOGRAPHY
1. Inverted T waves in precordial leads (V2 and V3) in the absence of right bundle branch block and people over 14 years (present in 85% of patients)
1. Epsilon wave or QRS prolongation (minimum 110 MS) in leads V1-V2;
2. Presence of late potentials;
3. Ventricular Arrhythmias
1. Sustained ventricular tachycardia or unsupported by left bundle branch block (ECG demonstrated on Holter or exercise testing);
2. Ventricular extra-systole (over 1000/24 hours).
1. Proven family history autopsy or surgical;
1. Family history of premature sudden death (under 35 years) with suspected ARVD;
2. Family history (suspicion based on clinical criteria).
Had been proposed other electrocardiographic criteria such as QRS and QT dispersion, defined as the difference between the parietal block QRS duration in V1, V2 or V3 and V6 bigger than 25 MS, the distance between the nadir S-wave and the isoelectric line V1, V2 or V3 at least 55 MS (present in approximately 95% of patients with ARVD) or V1 + V2 QRS ratio V3/V4 + + V5 + V6 ≥ 1.2. An inverted T wave in the right precordial leads in young people over 14 years is almost pathognomonic. Symptoms caused by ventricular rhythm disturbances can be completely asymptomatic from fatigue, syncope or cardiac arrest. For early detection of grade 1 ARVD relatives need at least one of the criteria in Table II 8.
1. Inverted T waves in right precordial lead V2-V3;
2. Late potentials present on the electrocardiogram with an amplified signal;
3. Ventricular tachycardia of left bundle branch block (ECG demonstrated on Holter or exercise testing);
4. Ventricular extra-systole (over 200/24 hours).
Structural and functional criteria
1. Overall moderate of the right ventricle dilatation and / or ejection fraction lower by keeping a normal function of the left ventricle;
2. Segmental moderate dilatation of the right ventricle;
3. Regional hypokinesia of the right ventricle;
Echocardiography provides basic information about the right ventricle suggestive of ARVD:
Hypokinesia and dilatation;
Dilation of isolated outflow tract;
Moderating intense band reflector-gene;
Dyskinesia / akinesis of the infero-basal segments and apex;
Standard imaging method in the diagnosis of ARVD is the right ventricular angiography but because it is invasive, has the exposure to ionizing radiation and has inter-observer variability is not commonly used. This highlights the akinetic / dyskinetic areas from the triangle of dysplasia. Another method that puts the patient to radiation is the computer tomography and can highlight:
Presence of wide areas with epicardial fat or intra-myocardial;
The right ventricular dilatation, aneurysm, hypokinesia.
Magnetic resonance imaging is ideal in ARVD diagnosis, providing information anatomical, morphological, functional (systolic and diastolic function assessment) and hemodynamics. Although it may reveal fatty infiltration of the myocardium to over 50% of the elderly population, replacing the myocardium with fatty tissue and diffuse thinning of the ventricular wall must be considered major criteria of ARVD.
Diagnostic criteria outlined by nuclear magnetic resonance are:
High intensity areas indicating replacement of myocardium with fatty tissue (major criterion);
Fibro-adipose tissue islands which causes diffuse thinning of the ventricular wall (major criterion);
Free wall aneurysm or outflow tract (major criterion);
Dilatation of the right ventricular and outflow tract (if severe-major criterion; if medium or minor-minor criterion);
Regional contractility abnormalities (minor criterion);
Systolic dysfunction (major criterion) and diastolic (minor criteria) overall.
Although histological diagnosis provided by endomyocardial biopsy is crucial, it is controversial because the samples taken are usually obtained from the septum. The risks of this technique are perforation and cardiac tamponade. The risk of cardiovascular death associated with the presence of clinical signs of the right ventricular failure, at least one episode of ventricular tachycardia with morphology of left bundle branch block and left ventricular dysfunction. The occurrence of sudden death is not directly related to disease progression, sudden death may be the first manifestation of the disease 11. Factors for which the prognosis depends in ARVD are: young age, family history of death in young people (under 35 years), QRS dispersion ≥ 40 MS, negative T waves, ventricular involvement, ventricular tachycardia, syncope and history of cardiac arrest.
1. Antiarrhythmic drugs:
Is most commonly used;
Beta-blockers are useful in reducing sympathetic activity;
Sotalol, at a dose of 320-480 mg / day is more effective than beta-blockers or Amiodarone in patients with inducible ventricular tachycardia or with not.
2. Catheter ablation:
Is recommended in cases of intolerance to antiarrhythmic therapy or ventricular tachycardia with high recurrent;
Has a success rate of 30-65%, which is difficult to eliminate all multiple outbreaks occurring gradually over time;
Targeting pathological substrate is characterized in terms of the potential electrophysiological low amplitude and fractionated (low driving velocity given by).
3. Implantable cardioverter defibrillator:
Is recommended in patients at high risk of death: cardiac arrest survivors with a history of syncope, ventricular arrhythmias not controlled by antiarrhythmic therapy, family history of cardiac arrest in first-degree relatives;
Can suppress ventricular tachycardia by stimulating the anti-tachycardia or electric shock;
Provide a safe and effective therapy, over 75% of implanted patients benefiting from it by an average of 3.5 years of follow-up;
Has a low rate of complications both short and long-term;
May encounter difficulties of the ventricular placement probe evidenced by where R amplitude inappropriate, high stimulation threshold, detection and inadequate stimulation, failure to reduce ventricular arrhythmias leading to increased defibrillation threshold;
May be complicated by perforation of the ventricle (thin wall less resistant because of body fat).
4. The heart failure therapy:
Diuretics, beta blockers, ACE inhibitors and anticoagulants;
Cardiac transplantation in case of refractory to treatment.
Is a cause of sudden death in young people (more athletic);
The diagnosis can sometimes be difficult and it is based on criteria like major and
electrocardiographic criteria are essential, in addition to family history of sudden death and structural and functional abnormalities of the right ventricular;
The therapy is medical and / or depending on the severity of the interventional
degree of risk.