Arrhythmias comprehensive panel

Although individually rare, inherited ion channel disorders collectively represent a substantial proportion of sudden cardiac deaths in young individuals, accounting for up to 40% of SCD cases in non‑athletes ≤35 years when structural heart disease is absent. has an estimated prevalence slightly above 1 in 2000, while varies globally (≈1 in 2000 to 1 in 5,000) depending on ethnicity. and are significantly rarer but carry disproportionately high arrhythmic risk.

Most cardiac channelopathies follow an autosomal dominant inheritance pattern with variable penetrance, enabling transmission from either parent to children with a 50% probability. Some rare recessive forms exist, such as certain Jervell–Lange‑Nielsen LQTS subtypes or autosomal recessive CPVT variants. Environmental and autonomic factors often modulate clinical expression, making family screening essential even in so‑called “mild” cases.

Diagnosis relies on ECG features, clinical history, family history, and specific provocation tests. Hallmark findings include QT interval prolongation or shortening (, ), coved ST‑segment elevation in , or exercise‑induced ventricular arrhythmias in CPVT. Many disorders require expert interpretation due to overlap with normal variants and autonomic influences. Genetic testing serves as a major adjunct to diagnosis, but sensitivity varies and negative results do not exclude disease. Since these conditions carry a high risk of sudden death—sometimes as the initial manifestation—early and accurate diagnosis is essential.

• In suspected inherited cardiac arrhythmia syndromes and ion channel disorders, molecular genetic testing can identify the causative pathogenic germline variant and thereby confirm or refine the clinical diagnosis. This is particularly relevant in channelopathies such as , , , and , where clinical features may be subtle, age-dependent, or overlapping.
• A molecular diagnosis can support risk stratification, clarify genotype-specific triggers and clinical manifestations, and guide individualised management. Depending on the gene and variant involved, genetic results may inform mechanism-based pharmacological therapy, avoidance of proarrhythmic medications, lifestyle and exercise recommendations, and the intensity of cardiac surveillance. Therapeutic decisions should always be made by the treating physicians in conjunction with the patient’s clinical findings and family history.
• Once a familial pathogenic variant has been identified, targeted cascade testing enables the detection of at-risk relatives before clinical events occur and allows non-carriers to be spared unnecessary follow-up. Genetic testing therefore contributes not only to diagnostic confirmation and personalized care of the index patient, but also to prevention, counselling, and family planning within the wider family.

• Dib Nehme R, Sinno L, Shouman W, Ziade JA, Ammar LA, Amin G, et al. Cardiac channelopathies: clinical diagnosis and promising therapeutics. J Am Heart Assoc. 2025;14(9):e040072. doi:10.1161/JAHA.124.040072. PMID: . PMCID: PMC12184234.
• Wilde AAM, Semsarian C, Márquez MF, Shamloo AS, Ackerman MJ, Ashley EA, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace. 2022;24(8):1307-1367. doi:10.1093/europace/euac030. PMID: . PMCID: PMC9435643.
• Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43(40):3997-4126. doi:10.1093/eurheartj/ehac262. PMID: .