Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Identify inherited cardiomyopathy and channelopathy red flags, investigate sudden unexplained death and organise expert family screening.
Inherited cardiomyopathies include hypertrophic, dilated and arrhythmogenic phenotypes; channelopathies include long-QT syndrome, Brugada syndrome and catecholaminergic polymorphic VT. Phenotype and genotype overlap, so evaluation is multidisciplinary.
After sudden arrhythmic death syndrome, the aim is not to assign a speculative label but to preserve samples, review expert pathology and systematically screen relatives. Findings must be communicated with psychological and reproductive support.
Pathogenic variants affecting sarcomeres, cytoskeleton, desmosomes or nuclear structures can produce hypertrophic, dilated or arrhythmogenic phenotypes. Fibrosis and ventricular remodelling create both pump failure and arrhythmic risk.
Variants affecting cardiac ion channels or calcium-handling proteins alter depolarisation, repolarisation or excitation–contraction coupling despite an apparently structurally normal heart. Long-QT, Brugada and catecholaminergic polymorphic VT phenotypes may remain concealed between triggers.
Storage, mitochondrial and neuromuscular disorders may involve myocardium or conduction tissue alongside renal, neurological, skeletal or sensory features. Recognising the wider phenotype guides appropriate genetic evaluation.
An inherited molecular abnormality may alter a structural protein, ion current or cellular metabolic pathway, even when no causal variant is yet identifiable. Dominant inheritance is common, but inheritance pattern and expression vary between conditions and within families.
Age, additional genetic factors and environmental exposure influence penetrance. Hypertrophy, dilatation, scar, conduction disease or an electrical abnormality may develop gradually and remain clinically silent.
Exercise, fever, sudden noise, medicines or electrolyte disturbance can interact with a susceptible substrate. The relevant trigger differs between conditions and may reveal previously concealed disease.
Triggered activity or re-entry can produce rapid ventricular tachycardia or fibrillation. Rapid VT may markedly reduce output, while ventricular fibrillation abolishes effective output and causes abrupt cerebral and coronary hypoperfusion.
Loss of cerebral perfusion causes syncope and may produce brief tonic movements mistaken for epilepsy. Sustained ventricular fibrillation is cardiac arrest and, without prompt CPR and defibrillation, leads to irreversible organ injury and death.
Sudden unexplained death before age 50, multiple premature deaths, unexplained drowning/road crash, cardiomyopathy or known familial variant.
Exertional or emotion-triggered syncope, palpitations with syncope, nocturnal agonal breathing or seizure-like episodes without neurological explanation.
Unexplained LV hypertrophy/dilatation, RV scar/dilatation, conduction disease, ventricular ectopy or disproportionate troponin/scar episodes.
Prolonged QT, Brugada type 1 pattern, bidirectional/polymorphic exercise-induced VT or unexplained ventricular fibrillation.
Skeletal myopathy, deafness, neuropathy, dysmorphism, renal/hepatic disease or learning disability may indicate a multisystem genetic diagnosis.
A prolonged upright posture, heat, pain, nausea and gradual prodrome favour reflex syncope. Collapse during exertion, supine events, palpitations or a family sudden death require cardiac assessment.
Focal onset, prolonged post-event confusion or a characteristic neurological history supports seizure. Arrhythmic cerebral hypoperfusion can still cause tonic movements, so sudden exertional episodes merit ECG and family review.
Coronary occlusion is a common acquired cause of ventricular arrhythmia and sudden collapse. Ischaemic symptoms, dynamic ST-segment change and coronary findings support it; troponin elevation alone after resuscitation is not specific for an acute occlusion.
Large emboli cause abrupt dyspnoea, syncope, hypoxaemia and sometimes cardiac arrest. Venous thromboembolic risk, right-heart strain and pulmonary vascular imaging identify the alternative mechanism.
Drug overdose, interacting QT-prolonging medicines and electrolyte disturbance can provoke ventricular arrhythmia without a primary inherited syndrome. A clear exposure and resolution after correction support an acquired cause, but a normal subsequent resting phenotype does not exclude concealed inherited susceptibility.
A concealed channelopathy or scarred cardiomyopathy may first present with ventricular tachycardia, fibrillation or cardiac arrest. Normal resting tests do not fully remove risk in a convincing family phenotype.
Inherited myocardial disease may progress from subtle remodelling to systolic, restrictive or right-ventricular failure. Declining function can coexist with arrhythmic risk and requires phenotype-specific surveillance.
Atrial enlargement and myocardial disease promote atrial fibrillation or flutter. Rapid rates may destabilise ventricular function, while atrial stasis can lead to systemic thromboembolism.
Some genetic cardiomyopathies and multisystem disorders damage the atrioventricular conduction system before severe pump failure. Bradycardia, syncope or sudden asystolic events may require pacing assessment.
Dominant inheritance and age-related penetrance mean asymptomatic relatives may carry clinically important risk. Failure to preserve post-mortem DNA or arrange appropriate family screening can miss opportunities to identify disease and reduce risk.
Testing an affected relative has a higher chance of an interpretable result than broad testing of an unaffected family member.
A negative panel does not erase a convincing familial cardiomyopathy; relatives may still need clinical surveillance.
Do not use a VUS to clear or diagnose relatives; segregation and future evidence may later change classification.
Transient cerebral hypoperfusion from ventricular arrhythmia can cause tonic movements; exertional or sudden episodes deserve ECG review.
Expert pathology and retained DNA can prevent speculative diagnoses and direct effective screening.
Reassuring a family after one normal ECG and echo.
Ordering a broad gene panel without phenotype or genetic counselling.
Using a variant of uncertain significance for predictive cascade testing.
Labelling exertional syncope as vasovagal without cardiac assessment.
Applying the same sports or ICD rule to every inherited condition.
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A 27-year-old dies suddenly and expert post-mortem examination finds no structural cause. What should be offered to first-degree relatives?
National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem ·