Can arrhythmia (irregular heartbeat) be inherited, especially in individuals with a family history of sudden cardiac death or congenital heart defects?

Is Arrhythmia Hereditary?

Yes, certain arrhythmias are definitively hereditary, with inheritable arrhythmogenic disorders identified in up to 50% of families with sudden cardiac death victims, particularly channelopathies like long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. 1

Understanding Inherited vs. Acquired Arrhythmias

Not all arrhythmias are hereditary—the distinction is critical:

• Inherited arrhythmia syndromes result from genetic mutations in genes encoding cardiac ion channels or regulatory proteins, causing conditions like long QT syndrome (mutations in KCNQ1, KCNH2, SCN5A genes), Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia in structurally normal hearts 1, 2

• Inherited cardiomyopathies include hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, which cause arrhythmias through structural heart abnormalities 1

• Acquired arrhythmias from coronary disease, hypertension, or valvular disease are not genetically transmitted, though familial clustering may occur due to shared environmental and lifestyle factors 1

Inheritance Patterns

Autosomal dominant inheritance is the most common pattern, meaning a 50% chance of transmission to offspring with each pregnancy 1:

• Romano-Ward syndrome (long QT without deafness) follows autosomal dominant inheritance 1
• Brugada syndrome demonstrates autosomal dominant transmission 1

Autosomal recessive inheritance occurs rarely but carries higher severity:

• Jervell Lange-Nielsen syndrome (long QT with congenital deafness) requires mutations from both parents and often involves consanguineous marriages 1

When to Suspect Hereditary Arrhythmia

Family screening is strongly recommended when first-degree relatives experience: 1

• Sudden unexplained death in individuals under 40 years old with structurally normal hearts 1, 3
• Recurrent premature sudden deaths across generations 1
• Documented inherited heart disease (channelopathies or cardiomyopathies) 1

Critical distinction: A family member with a cardiac stent indicates acquired atherosclerotic disease, fundamentally different from genetic arrhythmia syndromes that cause sudden death in young individuals 4

Recommended Evaluation Protocol for At-Risk Family Members

Comprehensive cardiac evaluation includes: 1, 4

• Personal clinical history focusing on syncope (especially during exercise, emotion, or acoustic stimuli), seizures, palpitations, presyncope, or unexplained near-drowning 1, 3
• Detailed multigenerational family pedigree documenting exact circumstances of deaths, ages at cardiac events, and autopsy findings 3
• Baseline 12-lead ECG with standard and high precordial leads to detect QT prolongation, Brugada pattern, or cardiomyopathy signs 1, 4
• 24-hour ambulatory ECG monitoring 1, 4
• Exercise stress test (critical for detecting catecholaminergic polymorphic ventricular tachycardia) 1, 4
• Two-dimensional echocardiography and/or cardiac MRI to exclude structural abnormalities 1, 4
• Provocative testing with sodium channel blockers when Brugada syndrome is suspected 1

Genetic testing should be directed by a cardiologist with expertise in inherited arrhythmias, with diagnostic yield 4 times higher when there is a survivor of sudden cardiac arrest compared to families with only sudden death 1, 3

Risk Stratification in Identified Cases

Long QT syndrome risk factors: 1

• QTc exceeding 500 ms identifies highest risk patients (upper quartile) 1
• LQT1 and LQT2 patients with QTc >500 ms have highest symptom risk by age 40 1
• Males with LQT3 carry higher risk regardless of QT interval duration 1
• Gene-specific triggers exist: LQT1 during exercise/swimming, LQT2 during rest/emotion/acoustic stimuli, LQT3 during sleep 1

Family history of sudden cardiac death itself has NOT proven to be an independent risk factor for sudden death in long QT syndrome once the diagnosis is established 1

Critical Pitfalls to Avoid

• Never rely on symptoms alone—many inherited cardiac conditions remain asymptomatic until a fatal event occurs 4, 3
• A normal resting ECG does not exclude life-threatening conditions like catecholaminergic polymorphic ventricular tachycardia or early hypertrophic cardiomyopathy 3
• Do not confuse acquired coronary disease with inherited arrhythmia syndromes—premature coronary disease (deaths <55 years in men, <65 years in women) suggests familial hyperlipidemia rather than channelopathies 4, 3
• Currently only 40% of family members undergo recommended screening, partially due to lack of infrastructure and anxiety associated with recent bereavement 1

Management Implications

Beta-blockers (specifically propranolol and nadolol) are first-line therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia 3, 2

Implantable cardioverter-defibrillator is recommended for: 1, 3

• High-risk individuals with documented ventricular arrhythmias 3
• LQT2 and LQT3 patients with syncope, torsades de pointes, or cardiac arrest despite beta-blocker therapy 1
• Specific high-risk features based on genotype and QTc duration 1

Multidisciplinary approach within specialized centers is essential, addressing both medical management and psychosocial needs of patients and families dealing with life-threatening inheritable conditions 1