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Familial Ventricular Tachycardia

Familial ventricular tachycardia is a multifactorial entity composed of long QT interval syndromes, arrhythmogenic right ventricular dysplasia, and hypertrophic cardiomyopathy. Catecholaminergic polymorphic ventricular tachycardia is another entity that can sometimes have a familial nature.


Presentation

These conditions are usually diagnosed after a major cardiac event happened, but their presentation can be widely variable.

An arrhythmogenic right ventricular dysplasia (ARVD) patient can be asymptomatic for some time, but will eventually complain about palpitations, caused by ventricular arrhythmias ranging from isolated ventricular ectopic beats to nonsustained and sustained ventricular tachycardia [1]. Others seek medical consult for biventricular failure, atypical chest pain, peripheral edema or dyspnea [2]. Syncope and sudden cardiac death, resuscitated or not [3] can be another clinical picture. As the disease progresses, the heart enlargement becomes global and the clinical picture resembles that of dilated cardiomyopathy, including the presence of supraventricular arrhythmias like atrial fibrillation and flutter [4]. Symptoms can be induced by physical effort, therefore the physician needs to carefully weight the differential diagnosis of arrhythmogenic right ventricular dysplasia, catecholaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy. An autosomal-recessive inherited ARVD case also exhibits specific extracardiac traits such as curly hair and palmoplantar keratosis.

Long QT syndrome patients have heterogeneous presentations since symptoms depend on their genotype. Cardiac events may occur during night sleep, during exercise or after exposure to intense emotions, cold water or auditory stimuli. When the individual also has a hearing deficit, Jervell and Lang-Nielsen syndrome becomes a plausible diagnosis. Scoliosis and short stature are traits of long QT 7 (Andersen) syndrome, while LQT8 (Timothy syndrome) individuals exhibit associated congenital heart diseases, immune dysfunction and musculoskeletal disorders, associated with cognitive impairment. Bradycardia at rest is encountered in all types of long QT syndrome.

When faced with a potential long QT syndrome patient, the physician must inquire about family history of sudden cardiac death, especially in young individuals and about the use of medication known to increase the QT interval.

Hypertrophic cardiomyopathy should be suspected in individuals complaining about palpitations, angina, dyspnea- both induced by effort and paroxysmal nocturnal, syncope or dizziness. Unfortunately, sudden cardiac death following intense physical effort can also be the presenting manifestation, especially in children. The mechanisms of death in these patients are ventricular fibrillation and low output ventricular tachycardia. Effort initially induces a supraventricular arrhythmia, such as atrial fibrillation or supraventricular tachycardia that subsequently degenerate to a malignant ventricular arrhythmia.

The physical examination of a familial ventricular tachycardia patient reveals different findings, depending on the substrate of the disease. Long QT interval syndromes and arrhythmogenic right ventricular dysplasia may not be accompanied by cardiac auscultation modifications, but hypertrophic cardiomyopathy patients often have specific findings, like S3 gallop, double or triple apical impulse, which is often laterally displaced and a typical, crescendo-decrescendo systolic ejection murmur. This is best heard between the left sternal border and the apex and radiates to the suprasternal notch. One should not mistake this murmur for that caused by aortic stenosis because the hypertrophic cardiomyopathy murmur is not audible in the auscultation areas of the carotid arteries. The murmur is best heard while standing, after Valsalva and Mueller maneuvers or squatting and decreases after handgrip or vasodilator administration. When a systolic anterior motion of the mitral valve is present, an additional apex and axilla holosystolic murmur can be heard. Auscultation can be completed by a diastolic murmur when significant aortic regurgitation coexists.

Short Stature
  • Scoliosis and short stature are traits of long QT 7 (Andersen) syndrome, while LQT8 (Timothy syndrome) individuals exhibit associated congenital heart diseases, immune dysfunction and musculoskeletal disorders, associated with cognitive impairment.[symptoma.com]
Regurgitation
  • Auscultation can be completed by a diastolic murmur when significant aortic regurgitation coexists.[symptoma.com]
Left Ventricular Dysfunction
  • One showed diffuse hypokinesis of the left ventricle by echocardiography and left ventriculography, 2 showed progressive left ventricular dysfunction and 1 showed regional perfusion defects of the left ventricle shown by thallium scintigraphy.[ncbi.nlm.nih.gov]
  • Página 148 - Randomised trial of effect of amiodarone on mortality in patients with left ventricular dysfunction after recent myocardial infarction: EMIAT. ‎ Página 148 - Moss AJ, Zareba W, Hall WJ et al.[books.google.es]
S3 Gallop
  • Long QT interval syndromes and arrhythmogenic right ventricular dysplasia may not be accompanied by cardiac auscultation modifications, but hypertrophic cardiomyopathy patients often have specific findings, like S3 gallop, double or triple apical impulse[symptoma.com]
Diastolic Murmur
  • Auscultation can be completed by a diastolic murmur when significant aortic regurgitation coexists.[symptoma.com]
Keratosis
  • An autosomal-recessive inherited ARVD case also exhibits specific extracardiac traits such as curly hair and palmoplantar keratosis. Long QT syndrome patients have heterogeneous presentations since symptoms depend on their genotype.[symptoma.com]
Palmoplantar Keratosis
  • An autosomal-recessive inherited ARVD case also exhibits specific extracardiac traits such as curly hair and palmoplantar keratosis. Long QT syndrome patients have heterogeneous presentations since symptoms depend on their genotype.[symptoma.com]
Impulsivity
  • Long QT interval syndromes and arrhythmogenic right ventricular dysplasia may not be accompanied by cardiac auscultation modifications, but hypertrophic cardiomyopathy patients often have specific findings, like S3 gallop, double or triple apical impulse[symptoma.com]
Akinesia
  • The first condition is characterized by right ventricular outflow tract dilatation, morphologic abnormalities, such as a hyperreflective moderator band and trabecular derangement and motion anomalies: regional akinesia, dyskinesia or localized aneurysm[symptoma.com]

Workup

Arrhythmogenic right ventricular dysplasia diagnosis is very difficult to establish and is based on major and minor criteria [5] referring to depolarization, repolarization and conduction abnormalities, global or regional dyskinesia as shown by various imaging methods, tissue abnormalities demonstrated by endomyocardial biopsy, Holter reports showing arrhythmia and family history.

When faced with a familial ventricular tachycardia patient, the physician must first demonstrate the familial character of the disease, and this is achieved by thorough anamnesis.

Blood tests should include serum levels of potassium and magnesium in patients suspected to have long QT syndrome. Thyroid function should be checked in all patients because increased circulating levels of thyroxin predispose to arrhythmia. Anemia is known to exacerbate dyspnea and chest pain, so it should be ruled out. In patients with severe left ventricle dysfunction, renal and liver function tests, as well as brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and troponin T levels should be measured.

The electrocardiogram may be the most important test in familial ventricular tachycardia patients. Arrhythmogenic right ventricular dysplasia patients exhibit depolarization/repolarization and conduction abnormalities [6] such as inverted T waves in right precordial leads [7] and epsilon waves located in the same territory, terminal activation of QRS =55 ms in V1-V3 when a right bundle branch block is absent and ventricular ectopic beats that originate in the right ventricle, thus having a left bundle branch block morphology. The long QT syndrome is characterized by increased QT interval duration and the presence of T-wave alternans- an indicator for increased risk of cardiac arrhythmias. T wave may be notched- often in long QT 2 syndrome (LQT2) or have a wide base- especially in LQT1. When torsade de pointes is observed, the diagnosis becomes even more plausible. The corrected QT interval (QTc) is also an important parameter, obtained by dividing the measured QT interval by the square root of the R-R interval. If longer than 0.46 seconds, this value indicates an increased likelihood of long QT syndrome. The QT interval may fail to properly adapt to an increased heart rate in this condition, as shown by Holter monitorization.

In hypertrophic cardiomyopathy, the electrocardiogram shows left ventricular hypertrophy, ST-T wave abnormalities, axis deviation, conduction abnormalities and atrial enlargement. A prominent Q wave in the anterior precordial and lateral limb leads should not be mistaken for a chronic myocardial infarction, instead, it should be correlated with the echocardiography aspect.

Echocardiography provides valuable information in arrhythmogenic right ventricular dysplasia and hypertrophic cardiomyopathy. The long QT syndrome has no specific echocardiography traits. The first condition is characterized by right ventricular outflow tract dilatation [8], morphologic abnormalities, such as a hyperreflective moderator band and trabecular derangement [9] and motion anomalies: regional akinesia, dyskinesia or localized aneurysm. In hypertrophic cardiomyopathy, echocardiography is a key investigation because it is able to differentiate between obstructive and non-obstructive forms. The obstructive type is diagnosed when the septum thickness exceeds 15 mm, it is asymmetrically hypertrophied, with a septal to posterior wall thickness above 1.4:1 and the systolic anterior motion of the anterior mitral valve leaflet is present. The left ventricular outflow tract is, therefore narrowed, thus explaining the characteristic auscultation.

Additional imaging methods like heart catheterization and magnetic resonance imaging are needed when more information is required, as these methods offer ideal image quality and fully characterize both ventricles. Twenty-four–hour Holter monitoring is necessary in all familial ventricular tachycardia patients in order to determine the frequency and advent circumstances of the arrhythmia. In patients with suspected LQTS, Holter monitoring reveals maladaptation of the QT interval to increasing heart rate. In hypertrophic cardiomyopathy, this tests highlights nonsustained ventricular tachycardia, as well as other types of atrial arrhythmia. In arrhythmogenic right ventricular dysplasia, the presence of ventricular tachycardia with left bundle branch block aspect and the superior axis is considered a major criterion, whereas ventricular tachycardia with an inferior or indeterminate axis or more than 500 ventricular extrasystoles are minor criteria.

Genetic testing can be performed in all three pathological entities [10] [11].

Right Bundle Branch Block
  • bundle branch block is absent and ventricular ectopic beats that originate in the right ventricle, thus having a left bundle branch block morphology.[symptoma.com]
  • Another possible pattern is alternating left and right bundle-branch block (see Figure 2 in the paper by Smith et al ). Bidirectional ventricular tachycardia Causes This rhythm is most commonly associated with severe digoxin toxicity .[lifeinthefastlane.com]
  • Another possible pattern is alternating left and right bundle-branch block (see Figure 2 in the paper by Smith et al ). Bidirectional ventricular tachycardia Causes This rhythm is most commonly associated with severe digoxin toxicity.[litfl.com]
Torsades De Pointes
  • Long QT syndrome patients that undergo treatment have a better prognosis, with only 4-5% fatalities caused by torsade de pointes.[symptoma.com]
  • [雑誌論文] A type 2 ryanodine receptor variant associated with reduced Ca2 release and short-coupled torsades de pointes ventricular arrhythmia. 2017 著者名/発表者名 Fujii Y, Itoh H, Ohno S, Murayama T, Kurebayashi N, Aoki H, Blancard M, Nakagawa Y, Yamamoto S,[kaken.nii.ac.jp]
T Wave Abnormality
  • In hypertrophic cardiomyopathy, the electrocardiogram shows left ventricular hypertrophy, ST-T wave abnormalities, axis deviation, conduction abnormalities and atrial enlargement.[symptoma.com]
T Wave Alternans
  • The long QT syndrome is characterized by increased QT interval duration and the presence of T-wave alternans- an indicator for increased risk of cardiac arrhythmias.[symptoma.com]
Prominent A-Wave
  • A prominent Q wave in the anterior precordial and lateral limb leads should not be mistaken for a chronic myocardial infarction, instead, it should be correlated with the echocardiography aspect.[symptoma.com]
Ventricular Hypertrophy
  • In hypertrophic cardiomyopathy, the electrocardiogram shows left ventricular hypertrophy, ST-T wave abnormalities, axis deviation, conduction abnormalities and atrial enlargement.[symptoma.com]

Treatment

Treatment of any familial ventricular tachycardia patient should be individualized according to the substrate of the disease. In arrhythmogenic right ventricular dysplasia, the cornerstone of therapy is represented by beta blockers. If they do not control symptoms, other antiarrhythmic agents like amiodarone, sotalol, propafenone or flecainide can be added. Amiodarone is less used in young patients because of its adverse effects accompanying long-term use [12]. Sudden cardiac death is best prevented in high-risk patients by means of an implantable cardioverter-defibrillator [13]. This decision is aided by genetic testing: if autosomal-dominant genotypes of the disease are present, implantation is highly recommended [14]. Radiofrequency ablation sometimes proves useful, but not always due to the patchy nature of the morphological abnormalities [15].

Beta blockers are drugs of choice in long QT syndrome, as well, as they prevent cardiac events in 70% of patients. Propranolol, nadolol, atenolol and metoprolol should be chosen, depending of the type of the syndrome. LQT3 has a poorer response to beta blockers compared to the other types [16]. The implantable cardioverter-defibrillator represents a valid therapeutic option in long QT syndrome, especially in high-risk patients, like those with aborted cardiac arrest or recurrent syncope or torsade de pointes. Recurrent discharges of the device can be prevented by performing cervicothoracic stellectomy in refractory cases. Long QT syndrome patients must also be advised to avoid a variety of drugs that can further elongate the QT interval: certain antihistamines, antibiotics, antiarrhythmic, antifungal and psychotropic drugs.

Beta-blockers are also used in hypertrophic cardiomyopathy, in order to control symptoms of the disease and arrhythmia. High blood pressure should be strictly controlled, as it exacerbates patient complaints. However, diuretics, nitrates and sympathomimetic amines, as well as digitalis should be avoided. Septal reduction therapy and transvenous catheter ablation of the septal region are curative measures that improve clinical status.

Prognosis

Arrhythmogenic right ventricular dysplasia is an important risk factor for sudden cardiac disease, accounting for 11% of cases. Long QT syndrome patients that undergo treatment have a better prognosis, with only 4-5% fatalities caused by torsade de pointes. However, those who receive appropriate beta blocker therapy and still have ventricular arrhythmia events must receive an implantable cardioverter-defibrillator in order to improve outcomes. LQT3 has a lower rate of response to pharmacological treatment and thus poorer prognosis. Hypertrophic cardiomyopathy individuals are amongst the highest-risk group for ventricular fibrillation, therefore their risk reduction by medical, interventional or surgical methods is imperative.

Etiology

Arrhythmogenic right ventricular dysplasia is transmitted in an autosomal dominant or autosomal recessive manner and is caused by abnormalities of chromosomes 14, 12, 10, 7, 6, 3, 2, or 1 [17] encoding desmocollin-2, plakoglobin, plakophilin-2, desmoplakin or desmoglein-2 genes [18]. Long QT syndromes are caused by either one of over 370 known mutations concerning sodium potassium and calcium channels and ankyrin-B. Familial hypertrophic cardiomyopathy has autosomal dominant transmission, but sporadic cases of abnormalities of 6 different genes located on 4 chromosomes can also be encountered. Anomalies of beta cardiac myosin heavy chain gene, located on chromosome 14 is often the cause of the disease.

Epidemiology

Arrhythmogenic right ventricular dysplasia and long QT syndrome are considered to be underdiagnosed, so epidemiological data are scarce. 1 in 1000-5000 individuals are considered to suffer from the first disease, while 1 in 2000-5000 patients have the latter. Hypertrophic cardiomyopathy is encountered in 0.05-0.2% of the population.

Sex distribution
Age distribution

Pathophysiology

Ventricular tachycardia in arrhythmogenic right ventricular dysplasia is caused by structural changes of the myocardium, like fibrosis and fatty infiltration. In long QT syndromes, abnormal potassium currents lead to early afterdepolarization. Transmural dispersion of repolarization represents the substrate for torsade de pointes. Hypertrophic cardiomyopathy is also characterized by a myopathic process and subendocardial ischemia that represent the substrate for ventricular arrhythmia.

Prevention

Genetic advice is recommended before conception or during the pregnancy for all parents that have familial ventricular tachycardia cases in their families. Patients suffering from any of the diseases belonging to this pathology cluster must avoid arrhythmia triggers like competitive sports, loud noises, swimming or medication that prolong the QT interval. Fever must be promptly eradicated. Patients that experience repetitive syncope and work in areas where these episodes can represent danger for themselves or others should be advised towards a career change.

Summary

Familial ventricular tachycardia can be due to several pathological entities, namely arrhythmogenic right ventricular dysplasia, long QT interval syndromes, catecolaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy. The substrate of the arrhythmia is diagnosed using personal and familial medical history and specific techniques, like electrocardiography, Holter monitorization, echocardiography, cardiac catheterization or magnetic resonance imaging. Beta blockers are useful in all cases, but additional antiarrhythmic agents may also be necessary. Some cases benefit from implantable cardioverter- defibrillators or surgical interventions. Patients should receive information about recommended lifestyle changes.

Patient Information

Familial ventricular tachycardia is a potentially serious condition caused by genetic abnormalities. Patients may experience palpitations, loss of consciousness, breathing difficulties or other signs of heart failure. When the physician suspects that you may suffer from one of the diseases that compose this pathology cluster, he or she will order tests like an electrocardiogram, echocardiogram, magnetic resonance imaging or catheterism. Treatment consists of pills that reduce the frequency of arrhythmic episodes, device implantation or cardiac surgery. Prognosis is good in most cases.

References

Article

  1. Dalal D, Nasir K, Bomma C, et al. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation. 2005;112(25):3823-32.
  2. Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural history and risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2004;110(14):1879-84.
  3. Maron BJ, Carney KP, Lever HM, et al. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41(6):974-80.
  4. Tonet JL, Castro-Miranda R, Iwa T, et al. Frequency of supraventricular tachyarrhythmias in arrhythmogenic right ventricular dysplasia. Am J Cardiol. 1991;67(13):1153.
  5. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121(13):1533-41.
  6. Nasir K, Bomma C, Tandri H, et al. Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to disease severity: a need to broaden diagnostic criteria. Circulation. 2004;110(12):1527-34.
  7. Marcus FI. Prevalence of T-wave inversion beyond V1 in young normal individuals and usefulness for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. Am J Cardiol. 2005;95(9):1070-1.
  8. Nava A, Bauce B, Basso C, et al. Clinical profile and long-term follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2000;36(7):2226-33.
  9. Yoerger DM, Marcus F, Sherrill D, et al. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia: new insights from the multidisciplinary study of right ventricular dysplasia. J Am Coll Cardiol. 2005;45(6):860-5.
  10. Awad MM, Calkins H, Judge DP. Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat Clin Pract Cardiovasc Med. 2008;5(5):258-67.
  11. Elliott PM, Anastasakis A, Borger MA, et al, for the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. Eur Heart J. 2014;35 (39):2733-79.
  12. Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Circulation. 1992;86(1):29-37.
  13. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2013;61(3):e6-75.
  14. Hodgkinson KA, Parfrey PS, Bassett AS, et al. The impact of implantable cardioverter-defibrillator therapy on survival in autosomal-dominant arrhythmogenic right ventricular cardiomyopathy (ARVD5). J Am Coll Cardiol. 2005;45(3):400-8.
  15. Verma A, Kilicaslan F, Schweikert RA, et al. Short- and long-term success of substrate-based mapping and ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia. Circulation. 2005;111(24):3209-16.
  16. Ahn J, Kim HJ, Choi JI, et al. Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: A meta-analysis. PLoS One. 2017;12(10):e0185680.
  17. Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2010;55(6):587-97.
  18. Bauce B, Nava A, Beffagna G, et al. Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm. 2010;(1):22-9.

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Last updated: 2019-07-11 20:05