Catecholaminergic polymorphic ventricular tachycardia (CPVT)

CPVT is a primarily autosomal dominant inherited disease. Rare variants in the CASQ2 (calsequestrin) and TECRL (trans-2,3-enoyl-CoA reductase-like) genes are detectable in about 3-5% of patients and lead to an autosomal recessive inherited form of CPVT.

A thorough clinical history is essential for diagnosing CPVT, particularly in individuals with a structurally normal heart and normal resting ECG who experience exertion‑ or stress‑induced palpitations, presyncope, syncope, seizure‑like episodes, sudden cardiac arrest, or have a family history of juvenile sudden cardiac death. CPVT typically manifests with two forms of polymorphic VT: a constantly shifting QRS morphology or the characteristic, though rare, bidirectional VT, which may also occur in digitalis intoxication. Exercise stress testing is the primary diagnostic tool and typically reveals a progression from isolated monomorphic ectopy to bigeminy and subsequently to polymorphic ventricular arrhythmias as workload increases. Exercise triggers polymorphic or bidirectional VT in about 63% of cases, meaning a negative exercise test does not exclude CPVT. In patients with high clinical suspicion but a negative standard exercise test, more specialised provocation protocols can be employed, and genetic testing represents an additional key diagnostic tool for confirming CPVT.

Main differential diagnoses include:

• type 1 (LQT1): exercise-triggered syncope without inducible arrhythmia on stress testing; KCNQ1
• Short-coupled ventricular tachycardia (SC-TdP): polymorphic VT in a structurally normal heart without adrenergic trigger; no established causal gene

• Confirming the clinical diagnosis at the molecular level resolves diagnostic uncertainty and supports integration of the genetic finding into the overall clinical picture.
• Identifying the underlying pathogenic variant enables specific and individualised surveillance and clinical management; it is the prerequisite for targeted medical care, which is determined by the treating physicians in consultation with the affected individual.
• Once the family-specific pathogenic variant is identified, predictive testing of at-risk relatives clarifies their individual genetic status and informs reproductive and preventive decision-making.

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