Is ventricular tachycardia (VT) a genetic (hereditary) condition?

Is Ventricular Tachycardia Genetic?

Yes, certain forms of ventricular tachycardia are definitively genetic, while others are not. The answer depends entirely on the underlying cause of the VT, with inherited channelopathies and cardiomyopathies representing the genetic forms, whereas idiopathic VT in structurally normal hearts typically lacks a familial basis.

Genetic Forms of Ventricular Tachycardia

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

CPVT is an inherited genetic disorder with clear autosomal transmission patterns. 1, 2

• Autosomal dominant form: Approximately 50% of cases are caused by mutations in the cardiac ryanodine receptor gene (RyR2) located on chromosome 1q42-43 1
• Autosomal recessive form: Caused by mutations in the calsequestrin gene (CASQ2), a calcium-buffering protein in the sarcoplasmic reticulum 1, 2
• The disease demonstrates clear familial clustering, with 33% of CPVT patients having a family history of sudden cardiac death 1
• Genetic testing confirms diagnosis in mutation carriers even before clinical manifestations appear 2
• Additional genes (KCNJ2, ANK2, TRDN, CALM1) have been identified but their role remains uncertain 2

Long QT Syndrome (LQTS)

LQTS represents another inherited channelopathy causing polymorphic VT (torsades de pointes). 1

• Autosomal dominant forms: Romano-Ward and Timothy syndromes are the most common patterns 1
• Autosomal recessive forms: Jervell Lange-Nielsen syndrome, often associated with congenital deafness and more severe phenotype 1
• Eight genes have been identified, with seven encoding cardiac ion channel subunits and one encoding an anchoring protein 1
• Genetic testing is useful in probands to provide accurate risk stratification and guide therapeutic strategies 1

Brugada Syndrome

This syndrome demonstrates genetic inheritance with incomplete penetrance. 1

• Mutations in the cardiac sodium channel gene (SCN5A) have been identified in a subset of patients 1, 3
• The disease shows autosomal transmission patterns, though specific mutations do not reliably predict clinical outcome 1
• Genetic analysis helps identify silent carriers for clinical monitoring and genetic counseling 1

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

ARVC has a well-established genetic basis affecting structural proteins. 1, 3

• Mutations in the cardiac ryanodine receptor gene have been identified in a subgroup of ARVC patients 3
• Naxos disease (a recessive form) involves mutations in the plakoglobin gene 3
• Genetic analysis is useful in families with RV cardiomyopathy for presymptomatic diagnosis and genetic counseling 1

Non-Genetic Forms of Ventricular Tachycardia

Idiopathic VT in Structurally Normal Hearts

These forms generally do NOT have a familial or genetic basis. 4

• Right ventricular outflow tract (RVOT) VT: The most common form of VT in apparently healthy people, associated with good prognosis and no genetic inheritance 1, 4
• Idiopathic left ventricular tachycardia (ILVT): Verapamil-sensitive fascicular VT without familial basis 4
• Idiopathic propranolol-sensitive VT (IPVT): No genetic component identified 4

VT Secondary to Acquired Structural Heart Disease

VT occurring after myocardial infarction, in dilated cardiomyopathy from non-genetic causes, or from inflammatory/infectious myocarditis is not inherited. 1, 5

Clinical Implications for Risk Assessment

When to Suspect Genetic VT

Look for these specific red flags that mandate genetic evaluation:

• Age of presentation: First syncopal episode before age 10-12 years strongly suggests genetic etiology 1, 2
• Trigger pattern: VT reproducibly induced by exercise, emotion, or stress (especially at heart rates >120 bpm) indicates CPVT 1, 2
• ECG morphology: Bidirectional VT (beat-to-beat alternating QRS axis by 180°) is pathognomonic for CPVT 1, 2
• Family history: Sudden unexplained cardiac death in young relatives (<40 years) or multiple family members with syncope 1
• Structurally normal heart: Absence of structural abnormalities on echocardiography and cardiac MRI despite recurrent VT 1
• Normal resting ECG: Particularly when VT is exercise-induced 2

When Genetic VT is Unlikely

• VT occurring in patients >40 years with coronary artery disease or prior myocardial infarction 1
• Monomorphic VT arising from RVOT in otherwise healthy adults without family history 1, 4
• VT associated with acute myocarditis, metabolic derangements, or drug toxicity 5

Genetic Testing Recommendations

Genetic analysis should be performed in all patients with suspected inherited arrhythmia syndromes. 1, 2

• Once a pathogenetic mutation is identified in a proband, cascade screening of family members becomes possible 1, 2
• Presymptomatic diagnosis allows early intervention with beta-blockers before clinical manifestations develop 1, 2
• Genetic counseling regarding transmission risk to offspring is essential 1
• Critical caveat: Genetic testing does not currently contribute to risk stratification in RV cardiomyopathy or predict which specific CPVT patients will experience cardiac arrest 1, 2

Management Differences Based on Genetic Etiology

For Confirmed Genetic VT (CPVT)

• First-line: Beta-blockers (nadolol preferred) plus exercise restriction for all genetically confirmed cases, even asymptomatic mutation carriers 1, 2
• Second-line: Add flecainide if recurrent syncope or VT occurs despite beta-blockers 2
• Third-line: Left cardiac sympathetic denervation for refractory cases 2
• ICD implantation is indicated for cardiac arrest survivors and those with syncope on beta-blockers 1, 2
• Electrophysiology studies are NOT useful because CPVT is not inducible with programmed ventricular stimulation 1, 2

For Non-Genetic Idiopathic VT

• Catheter ablation is first-line curative therapy for symptomatic RVOT VT 1
• Beta-blockers or calcium channel blockers can be used if ablation is declined 1
• ICD is rarely needed unless VT is sustained and hemodynamically unstable 1

Common Pitfalls to Avoid

• Do not assume all young patients with VT have genetic disease: Idiopathic RVOT VT is common in healthy teenagers and young adults without genetic basis 1, 4
• Do not rely on electrophysiology studies for CPVT diagnosis or risk stratification: The arrhythmia is not inducible with programmed stimulation 1, 2
• Do not withhold beta-blockers from genetically positive family members with negative exercise tests: Prophylactic therapy is indicated 2
• Do not assume a negative genetic test excludes inherited disease: Only 50% of CPVT cases have identifiable RyR2 mutations, and other genes remain undiscovered 1, 2