Self-assessment questions

ACM is characterised by fibrofatty myocardial replacement, ventricular arrhythmias and sudden-death risk; it may be right, left or biventricular.

Guidance describes ARVC as right-dominant, ABVC as biventricular and ALVC as left-dominant.

PKP2 is listed as the most common gene and is associated with classic RV-dominant ARVC.

Ring-like LGE in at least three Bull’s Eye segments is highlighted as a hallmark of ALVC, especially DSP/FLNC/PLN.

Guidance states that endurance and high-intensity exercise can accelerate disease and should be avoided in diagnosed ACM.

Guidance states definite ACM requires 2 major, or 1 major + 2 minor, or 4 minor criteria from different categories.

Beta-blockers are listed as Grade I first-line therapy for patients with arrhythmias, dosed as high as tolerated.

Guidance lists flecainide as an add-on if beta-blocker alone is insufficient and states not to use it as monotherapy.

Guidance lists survivors of cardiac arrest or sustained VT causing syncope/haemodynamic compromise as Class I ICD indications.

Guidance lists myocarditis and cardiac sarcoidosis among phenocopies/mimics that can fulfil diagnostic criteria but are not genetic ACM.

An appropriate shock is a secondary-prevention event and carries a six-month Group 1 restriction. A primary-prevention implant requires one month, and an inappropriate shock two weeks provided the cause has been corrected.

Any ICD is a permanent bar to Group 2 licensing. A pacemaker alone may be compatible with Group 2 if the underlying condition allows, subject to DVLA assessment. Group 2 standards also generally treat any syncope or near-syncope within five years as disqualifying.

Pregnancy raises sympathetic tone and volume load, which can increase arrhythmic risk. Beta-blockers are continued at the maximum tolerated dose and epidural analgesia is generally preferred because it blunts the catecholamine response. Mode and timing of delivery are decided by the Pregnancy Heart Team on the basis of functional status and arrhythmia history rather than a fixed rule. Resuscitation equipment including a defibrillator should be available for delivery.

ACM carries among the stricter exercise restrictions of the cardiomyopathies because of the “exercise paradox”: endurance and high-intensity exercise can accelerate disease progression, and even moderate exercise may worsen the phenotype. Moderate-intensity recreational activity may still be considered after specialist review and shared decision-making, so this is individualised rather than an absolute prohibition.

The general matrix row for gene-positive, phenotype-negative individuals permits low, moderate and vigorous intensity with annual review, treating competitive sport as a shared decision. ACM is the important exception to read carefully: exercise dose is associated with age-related penetrance and arrhythmic risk in desmosomal variant carriers, so this population warrants individualised specialist advice rather than the generic row.

A negative genetic result does not exclude inherited disease. Genotype-negative disease is well recognised in ACM/ARVC, HCM, DCM and Brugada syndrome. Where the proband has no identifiable pathogenic variant, cascade genetic testing is not possible and relatives are followed with clinical screening instead.

DCM is defined by LV or biventricular dilatation and systolic dysfunction after excluding abnormal loading conditions and coronary artery disease.

Guidance lists LVEF <45% and LVEDD >117% predicted, with exclusion of alternative causes.

TTN truncating variants, especially in the A-band, are the commonest genetic finding in DCM.

LMNA cardiomyopathy commonly shows conduction/arrhythmic disease before overt DCM and carries high arrhythmic risk.

Guidance lists ACEi/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist and SGLT2 inhibitor. The 2026 ESC heart failure guideline renames this group foundational medical therapy (FMT); “GDMT” and “four pillars” are retired terms, though the four drug classes themselves are unchanged.

Guidance lists primary-prevention ICD for LVEF ≤35% despite ≥3 months of foundational medical therapy, with NYHA II–III and suitable life expectancy. The ≤35% device threshold comes from the ESC 2022 ventricular arrhythmia/SCD guideline and is unchanged by the 2026 heart failure phenotype revision.

The DCM section notes that LGE presence, location and extent inform SCD risk beyond LVEF alone.

Guidance lists myocarditis, alcohol, tachycardia-mediated cardiomyopathy, peripartum, chemotherapy, thyroid and nutritional causes as acquired causes to exclude.

Guidance lists LMNA ICD consideration when at least two risk factors are present: NSVT, LVEF <45%, male sex and non-missense variant.

Guidance lists LVEF <30% or NYHA III–IV as mWHO IV, where pregnancy is contraindicated.

For Group 1, DCM that is asymptomatic with LVEF above 40% is compatible with driving, with annual review. If symptomatic or LVEF is 40% or below, the driver must notify DVLA and cease driving if symptomatic. Group 2 requires LVEF of 45% or more with no symptomatic heart failure and no significant arrhythmia.

A primary-prevention ICD requires one month off Group 1 driving. This differs from the secondary-prevention situation: after an appropriate shock the restriction is six months, and after an inappropriate shock it is two weeks provided the cause has been corrected.

Notification is the patient’s responsibility. The patient must also stop driving if told to do so or if the condition worsens, attend reviews as required (typically every one to three years) and inform their car insurer of the medical condition.

ACE inhibitors, ARBs and sacubitril/valsartan are fetotoxic and are stopped pre-conception. Spironolactone is antiandrogenic and is avoided or switched to eplerenone, and SGLT2 inhibitors are stopped because human data are inadequate. Beta-blockers and, where needed, furosemide and digoxin are generally continued.

Low molecular weight heparin is the anticoagulant of choice in pregnancy because it does not cross the placenta, though it requires dose adjustment and monitoring. DOACs are contraindicated: they cross the placenta, show fetal and embryo toxicity in animal studies and have no human safety data. Warfarin has a specific, restricted role in mechanical valve disease only.

Competitive sport is advised only when LVEF is above 50% with no LGE and a normal exercise test, and is contraindicated below 50%. Vigorous exercise is contraindicated if LVEF is under 45% or the patient is symptomatic, and any exercise is contraindicated during decompensation. LMNA variants warrant careful monitoring regardless of LVEF.

Only a pathogenic or likely pathogenic variant that has been shown to fit the phenotype enables cascade testing of relatives. A VUS is not a diagnosis, must not be used to justify predictive testing, and does not alter the need for clinical family screening, which continues on phenotype regardless of the variant’s classification.

Fabry disease is an X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A activity.

Fabry disease is caused by pathogenic variants in GLA on Xq22.1.

Fabry disease is X-linked; males are hemizygous and females can be variably affected due to X-inactivation.

Guidance states enzyme activity is often normal in females, so GLA sequencing is mandatory for diagnosis and cascade screening.

Classic Fabry disease includes angiokeratomas, acroparesthesias, hypohidrosis/corneal verticillata, renal, cardiac and cerebrovascular disease.

Guidance lists concentric LVH, inferolateral mid-wall LGE and low T1 values as Fabry CMR features.

Fabry therapy includes agalsidase alfa/beta enzyme replacement and migalastat chaperone therapy for amenable GLA variants.

Migalastat is an oral chaperone used only for amenable GLA variants and is dosed every other day.

Guidance recommends alpha-Gal A enzyme testing in all males with unexplained LVH, especially with red flags.

Migalastat has no human pregnancy data and is stopped pre-conception. Continuation of enzyme replacement therapy may be considered where clinically indicated after specialist discussion, though the supporting evidence is reassuring but limited to case series. ACE inhibitors and ARBs are stopped pre-conception, and echocardiography with renal function is monitored each trimester.

Phenotype precedes genotype. Acquired causes and phenocopies must be excluded before an inherited diagnosis is assigned, because the clinical syndrome guides test selection. Fabry disease is a treatable phenocopy of HCM, so recognising it changes management as well as the genetic pathway followed.

HCM is defined as LV hypertrophy that is not solely explained by loading conditions such as hypertension or valvular disease.

The ESC diagnostic threshold in adults is LV wall thickness ≥15 mm in one or more myocardial segments, not explained solely by loading conditions.

With a family history of HCM, a lower threshold of ≥13 mm is used.

MYBPC3 and MYH7 are the two commonest sarcomeric genes listed, together forming a major proportion of genotyped HCM.

Guidance lists NSVT, unexplained syncope, massive LVH and family history of SCD among HCM high-risk markers.

Guidance identifies the HCM Risk-SCD calculator for adults ≥16 years.

Guidance states that anticoagulation is mandatory in HCM with AF regardless of CHA2DS2-VASc score.

Guidance warns not to combine verapamil with beta-blockers because of risk of complete AV block and haemodynamic collapse.

Guidance notes mavacamten is contraindicated in pregnancy and should be interrupted if LVEF falls below 50%; CYP2C19 status affects dosing.

Guidance highlights amyloidosis, Anderson-Fabry disease and mitochondrial disorders as HCM phenocopies.

Whether DVLA notification is required depends on the condition, current symptoms and licence group, not a single blanket rule. For an isolated HCM diagnosis a Group 1 (car/motorcycle) driver generally does not need to notify DVLA unless another disqualifying feature is present. A Group 2 (bus/lorry) driver must notify DVLA of the diagnosis. Each case is assessed individually. Disqualifying features to look for include syncope, sustained arrhythmia and significant left ventricular outflow tract obstruction.

Group 2 licensing applies a higher medical standard than Group 1 because of the greater public-safety risk, and the burden of proof is on the applicant to demonstrate fitness rather than merely the absence of disqualifying features. Specialist review is typically annual and DVLA may issue shorter-duration licences. The Group 2 standard requires an LVOT gradient below 30 mmHg, wall thickness under 30 mm, no syncope, no non-sustained VT, a normal blood-pressure response to exercise and an LVEF of 45% or more.

Mavacamten has no human pregnancy data and animal reproductive toxicity, so it is stopped pre-conception with effective contraception. Disopyramide is uterotonic and may stimulate contractions, particularly in the first trimester. Beta-blockers (bisoprolol or metoprolol preferred) are generally continued, with verapamil an option if beta-blockers are not tolerated.

mWHO classifies maternal cardiovascular risk from I (no detectable increase in mortality, local obstetric care) to IV (extremely high maternal risk requiring detailed individualised counselling before conception). The class listed for a condition is a starting point rather than a fixed assignment: risk should be individualised by a Pregnancy Heart Team using modifiers such as ventricular function, arrhythmia history, aortic dimensions and genotype. The class guides where care is delivered and how often review occurs.

High-risk features warranting restriction include prior exertional syncope or presyncope, sustained ventricular arrhythmia or cardiac arrest, a family history of sudden cardiac death in young relatives, severe LVH of 30 mm or more, extensive LGE (15% or more of LV mass), LVOT gradient above 50 mmHg, apical aneurysm, LVEF below 50%, NSVT, an abnormal BP response to exercise, or an HCM Risk-SCD score of 6% or more.

Low intensity is below 3 METs and under 50% of maximum heart rate, with conversation held easily. Moderate is 3–6 METs at 50–70% of maximum heart rate. Vigorous is above 6 METs at 70–85%, where talking is difficult. Competitive sport is defined separately by organised training and a performance focus.

Genetic testing is most informative in an affected proband with a well-defined phenotype. Phenotype comes before genotype: the clinical syndrome guides which test is chosen, not the reverse. The aim is to confirm a diagnosis, refine prognosis in selected conditions, enable cascade testing and support reproductive counselling.

Marfan syndrome is an autosomal dominant connective tissue disorder caused by FBN1 variants.

Guidance states first-degree relatives have a 50% risk of inheriting the pathogenic variant.

Revised Ghent criteria include aortic root dilatation/dissection plus ectopia lentis in the absence of family history.

Echocardiography measures aortic-root dimensions at the sinuses of Valsalva using age/BSA Z-scores.

Guidance lists beta-blockers such as atenolol as first-line medical therapy to reduce aortic growth rate.

Guidance lists losartan as additive to beta-blocker but to avoid in pregnancy and switch before conception.

Guidance lists prophylactic aortic-root replacement at ≥50 mm, or ≥45 mm if risk factors are present.

Guidance lists family history of dissection, rapid growth >3 mm/year or concurrent surgery as factors for a lower ≥45 mm threshold.

Guidance lists aortic root >45 mm, prior aortic dissection or rapid growth as mWHO IV/contraindicated/highest risk scenarios.

Guidance advises avoiding heavy lifting, isometric exercise, contact sports and competitive sports; low-intensity aerobic activity is generally acceptable.

Both Group 1 and Group 2 licensing in Marfan syndrome and aortopathy are assessed individually rather than against a fixed diameter, considering blood pressure control, aortic dimensions and absence of a dissection history. Always check the current DVLA cardiovascular guidance.

Losartan and ACE inhibitors are teratogenic and are stopped pre-conception, while the beta-blocker is continued. Aortic imaging is typically every four to six weeks during pregnancy, and postpartum imaging is repeated because dissection risk persists after delivery. Risk should be individualised by an aortopathy and Pregnancy Heart Team rather than judged against a single diameter cut-off.

Vigorous exercise is contraindicated at all root sizes under ESC 2020. Moderate-intensity activity is restricted to a root below 40 mm and to non-contact activity, and contact or collision sport and competitive sport are contraindicated. Low-intensity exercise is permitted.

Cascade testing depends on first identifying a pathogenic or likely pathogenic variant in the proband and confirming that it fits the phenotype. A variant of uncertain significance does not support predictive testing. Relatives who test negative for a confirmed familial variant can usually be discharged from cardiac surveillance for that condition.

LQT1 arises from loss-of-function variants in KCNQ1 (Iₖₛ current). KCNH2 causes LQT2, SCN5A causes LQT3, and RYR2 is the principal CPVT gene.

LQT1 accounts for roughly 50% of genotype-positive cases, LQT2 for about 35–40%, and LQT3 for about 10%; the remaining genotypes are individually rare.

Exercise, and swimming in particular, is the characteristic LQT1 trigger, which is why avoiding competitive swimming is a genotype-specific precaution in LQT1.

LQT2 events are characteristically provoked by sudden loud noises or abrupt awakening, and LQT2 carries the highest arrhythmic risk in the postpartum period.

LQT3 (SCN5A, persistent late sodium current) characteristically causes events at rest or during sleep, with a long isoelectric ST segment and a late T wave. Mexiletine is the genotype-directed add-on where indicated.

LQT2 is associated with low-amplitude notched or bifid T waves; LQT1 typically shows broad-based T waves, and LQT3 a long isoelectric ST segment with a late T wave. Morphology supports, but does not replace, genetic testing.

A Schwartz score of ≥3.5 in the absence of a secondary cause indicates a high probability of LQTS. The score combines ECG, clinical and family-history criteria.

A repeated QTc ≥500 ms with no secondary cause can support the diagnosis; a QTc ≥480 ms carries more weight when there is unexplained syncope. Borderline values alone are not diagnostic.

Normal electrolytes are a general measure in LQTS: target K⁺ 4–5 mmol/L, and 4.5–5 mmol/L in LQT2 where Iₖᵣ is particularly sensitive to hypokalaemia. Avoid hypokalaemia, hypomagnesaemia and high-dose diuretics.

Nadolol is preferred for its long action and consistent levels; it is not routinely stocked in the UK and is arranged through hospital pharmacy. Propranolol is the usual alternative. Sotalol prolongs the QT interval and is not used here.

A normal QTc does not exclude LQTS in a genotype-positive person. Drug precautions, electrolyte targets and follow-up still apply, and the QT-prolonging drug list should still be checked before any prescription.

Genotype, symptom history, QTc and current therapy are weighed together rather than mapped onto one fixed class. LQT2 carries the highest event risk in pregnancy and especially postpartum, so beta-blockade is continued and close follow-up maintained for around nine months after delivery.

Only the Type 1 pattern is diagnostic: coved ST elevation of at least 2 mm followed by a negative T wave in one or more right precordial leads. Type 2 and Type 3 patterns are not diagnostic on their own and require provocation testing or further assessment.

Lead placement matters: recording V1–V2 in the 2nd and 3rd intercostal spaces unmasks a Type 1 pattern that standard placement can miss. This applies to family screening ECGs as well.

SCN5A is identified in only around 20–30% of cases, a lower yield than the other channelopathies. Testing is still recommended, because an identified variant enables cascade screening; a negative result does not exclude the diagnosis.

Despite autosomal dominant inheritance affecting both sexes equally, clinical events show a marked male predominance, on the order of 8–10:1.

Provocation testing carries real risk and is not appropriate for an asymptomatic person with a Type 2 pattern and no family history, where a positive result would not change management proportionately. It remains appropriate where the pre-test probability and clinical consequences justify it.

A drug-induced Type 1 pattern in isolation, without symptoms or family history, is not diagnostic and is a recognised pitfall of the drug challenge test. Such patients are in the lower-risk group and an ICD is generally not indicated.

Fever is a recognised trigger for ventricular fibrillation in Brugada syndrome, accounting for a small but important proportion of presentations, and should be treated promptly. This advice applies in pregnancy as well.

Programmed electrical stimulation has limited and controversial incremental value in Brugada syndrome. It may be considered in selected asymptomatic patients with a spontaneous Type 1 pattern, but not as a stand-alone ICD indication.

Quinidine blocks Iₜₒ, normalising ST elevation and suppressing VF triggers. In the UK it is an unlicensed or SPECIALS product needing specialist pharmacy sourcing, and it requires QTc monitoring because it can paradoxically prolong the QT interval. Isoprenaline is used for acute electrical storm.

Autosomal dominant gain-of-function variants in RYR2, the cardiac ryanodine receptor, account for around 55–65% of CPVT. SCN5A and KCNQ1 are long QT and Brugada genes; LAMP2 causes Danon disease.

CASQ2 (calsequestrin 2) CPVT is autosomal recessive and uncommon, at roughly 2–5% of cases. The recessive pattern changes the cascade-screening conversation with the family, since parents are usually unaffected carriers.

A normal resting ECG does not exclude CPVT: the diagnosis rests on reproducible exercise-induced ventricular ectopy or bidirectional or polymorphic VT, so the exercise test must be taken to maximal exertion and should not be curtailed.

Bidirectional VT, in which the QRS axis alternates on successive beats, is characteristic of CPVT, though polymorphic VT is also seen. Ectopy typically emerges at a reproducible heart rate threshold and increases with workload.

Digoxin toxicity is the classic mimic, producing bidirectional VT through a comparable mechanism of calcium overload. Drug history and a digoxin level belong in the assessment before the arrhythmia is attributed to CPVT.

Beta-blockade at the maximum tolerated dose is first-line for every diagnosed patient, symptomatic or not, with nadolol preferred. Abrupt withdrawal can be fatal. An ICD does not replace medical therapy.

Flecainide is added when there are breakthrough events or very high risk, and is always combined with a beta-blocker. QRS widening beyond about 25% prompts review, and the dose is reduced in renal impairment.

Beta-blocker monotherapy gives significant but incomplete protection, at around 60–70% event reduction; adding flecainide raises this to roughly 80–90%. Left cardiac sympathetic denervation adds further protection where drug therapy is insufficient.

Painful shocks increase sympathetic tone and can precipitate further arrhythmia, including VF storms. Medical therapy is maximised first, and beta-blockers are continued after implantation. Secondary prevention after cardiac arrest, or syncope despite optimal therapy, remain clear indications.

A QTc of ≤320 ms is a stand-alone diagnostic criterion. A QTc of 320–360 ms supports the diagnosis when accompanied by features such as a pathogenic variant, a family history, or unexplained cardiac arrest.

The yield is low, at roughly 20%, so a negative result does not exclude the diagnosis. A gene-validity reappraisal has reduced the number of genes considered to have robust evidence.

Gain-of-function variants in KCNH2 increase Iₖᵣ, shortening repolarisation; this is SQT1, the gene with the strongest evidence. Loss of function in the same gene causes LQT2, the opposite phenotype.

Acquired QT shortening from hypercalcaemia, hyperkalaemia, acidosis or digoxin must be excluded first. Accurate measurement across several leads, using more than one correction formula, is equally important.

The Gollob score is an earlier proposed diagnostic scoring system. It is described separately from the current guideline criteria, which use QTc thresholds together with clinical and family-history features, so the two should not be conflated.

Short QT syndrome is inherited in an autosomal dominant pattern, giving first-degree relatives a 50% prior risk, so family screening is essential. Where a pathogenic variant is identified, cascade genetic testing can be offered alongside ECG assessment.

Perugini grade 2–3 uptake with no monoclonal protein detected gives a non-biopsy diagnosis of ATTR-CM with near-complete specificity. Both halves are required: imaging alone is not enough.

Bone scintigraphy can be positive in AL amyloidosis too, so a monoclonal protein alongside a positive scan invalidates the non-biopsy pathway. Biopsy with typing by mass spectrometry or immunohistochemistry is then required.

All three components are needed. Protein electrophoresis alone is insufficient and is a recognised way for a low-level plasma-cell dyscrasia to be missed, which would make a positive bone scan misleading.

Wild-type and hereditary ATTR are indistinguishable on imaging. Sequencing separates them, and identifying ATTRv triggers cascade screening of first-degree relatives.

ATTRwt is the commonest cardiac form in the elderly and is acquired rather than inherited, so it carries no implications for relatives. Hereditary ATTRv and AL are the other two forms to distinguish.

V122I is the commonest ATTRv variant in Black patients, with a carrier frequency around 3–4%. V30M is common in Portuguese and Japanese populations. Inheritance is autosomal dominant, so first-degree relatives should be screened.

The mismatch between thick walls on imaging and low voltages on the ECG is the classic clue, because infiltrate rather than myocyte hypertrophy causes the wall thickening. Bilateral carpal tunnel syndrome, lumbar canal stenosis and intolerance of ACE inhibitors or beta-blockers are other recognised red flags.

Tafamidis is a TTR stabiliser and was the first therapy shown to reduce mortality and cardiovascular hospitalisation in ATTR-CM. Because benefit is greatest early, disease-modifying therapy should not be deferred. Acoramidis is a newer stabiliser, and vutrisiran is a gene silencer with cardiovascular benefit in HELIOS-B.

A relatively fixed stroke volume and marginal blood pressure mean these agents are frequently not tolerated, and digoxin binds amyloid fibrils. Loop diuretics, often at high doses, remain the mainstay for congestion, and an MRA is recommended in symptomatic heart failure irrespective of ejection fraction.

Untreated AL amyloidosis with cardiac involvement carries a median survival of around six months, so referral is urgent. Daratumumab-based regimens are first-line following ANDROMEDA, and the Mayo stage drives prognosis and transplant eligibility.

Danon disease results from variants in LAMP2 on Xq24 and is inherited in an X-linked dominant pattern. LAMP2 is integral to autophagy, and its loss produces intracytoplasmic vacuoles containing autophagic material.

Hemizygous males lack LAMP2 entirely and have early, severe disease with high mortality. Females are affected but later and more variably because of X-inactivation mosaicism, and they must not be dismissed as unaffected carriers.

The triad is complete in about 42% of males and is rare in females, so its absence does not exclude the diagnosis. Skeletal myopathy is present in roughly half of cases and cognitive impairment in about 56%, predominantly in males.

Pre-excitation is found in roughly 40% of patients with no clear difference between the sexes, and conduction abnormalities in around 58%. Severe LVH combined with pre-excitation and a raised creatine kinase in a young male is highly suggestive, though LAMP2 testing is still needed to confirm it.

Around 29% of affected females present with a dilated phenotype, against under 4% of males, so restricting LAMP2 testing to hypertrophic phenotypes will miss them. All first-degree female relatives should be screened.

There is no disease-modifying therapy; standard heart-failure treatment is given but disease is often refractory, with about 44% reaching end-stage cardiomyopathy and around 20% requiring transplantation. An ICD is commonly considered even with preserved ejection fraction, though the Danon-specific evidence is limited and extrapolated. Gene therapy and substrate reduction remain investigational.

Pompe disease is an autosomal recessive lysosomal storage disorder caused by acid α-glucosidase deficiency, leading to lysosomal glycogen accumulation. α-galactosidase A deficiency is Fabry disease, LAMP2 loss is Danon disease, and TTR misfolding causes hereditary amyloidosis.

The infantile form combines severe cardiomyopathy with massive hypertrophy, a short PR interval and muscle weakness, and is fatal within the first year without treatment. The other presentations point towards CPVT, cardiac amyloidosis and Danon disease respectively.

Juvenile and adult-onset disease is dominated by proximal weakness and respiratory muscle involvement, with cardiac involvement less prominent, so respiratory assessment and non-invasive ventilation are central to management.

The dried blood spot is a screening test; a low result must be confirmed by a second method — an enzyme assay on alternative tissue, or GAA gene sequencing. In infantile-onset disease, CRIM status should also be determined before enzyme replacement therapy, because it predicts the immune response to treatment.

Outcomes in infantile-onset disease depend on early treatment and CRIM status, so enzyme replacement should not be delayed. Alglucosidase alfa dramatically improved survival in the infantile form; avalglucosidase alfa met non-inferiority for respiratory function in COMET, and the choice of agent follows licensing and specialist guidance.

A short PR interval alongside voltage criteria for LVH is characteristic in Fabry disease. Low voltage with thick walls points instead towards cardiac amyloidosis. Conduction disease and bradyarrhythmia can develop later and may require pacing.

Lyso-Gb3 is the disease-specific biomarker, checked alongside renal function at follow-up. Serum free light chains belong to the amyloidosis pathway and a raised creatine kinase points towards Danon or Pompe disease.

Enzyme replacement and chaperone therapy improve outcomes but do not reverse established fibrosis, so the window for benefit closes as late gadolinium enhancement develops. T1 mapping on CMR can detect involvement before overt hypertrophy appears.

Genetic counselling by an appropriately trained professional, including genetic education and psychosocial support, is a Class I recommendation for families with an inherited or suspected inherited cardiomyopathy regardless of whether testing is planned. Counselling is a process of helping families understand and adapt to the medical, psychosocial and familial impact of a genetic condition; it includes a three-generation family history, discussion of inheritance and the need for clinical evaluation, and pre- and post-test sessions when testing does go ahead.

The ESC 2023 guideline lists the key pre-test discussion points: a detailed family history, genetic education, the process and logistics of testing, all possible outcomes, implications for clinical care, lifestyle and employment, implications for the family, the risk of reclassification, secondary genetic findings, potential insurance implications (country dependent), and psychosocial support. Pre- and post-test counselling is a Class I recommendation for every person undergoing cardiomyopathy genetic testing, irrespective of panel size, prior counselling of relatives, or the eventual result. The JCGM 2019 guidance makes the same points for UK practice: consent discussions should cover familial implications, the possibility of unexpected findings and that interpretation may be updated later.

The Class I indication for testing a proband depends on it enabling diagnosis, prognostication, therapeutic stratification, reproductive management, or cascade evaluation of relatives. Where none of these applies, the guideline still allows testing to be considered (Class IIb, Level C) when it will have a net benefit to the patient, taking into account the psychological impact and the patient's own preference. The right to know is respected, but the decision should follow counselling rather than an automatic order.

Genetic testing of a deceased individual found to have a cardiomyopathy at post-mortem is a Class I (Level C) recommendation when a genetic diagnosis would facilitate management of surviving relatives. In England this is delivered through the National Genomic Test Directory on the matching condition panel (R131 for HCM), which explicitly includes deceased individuals with pathologically confirmed HCM. Consent for using stored tissue is governed by the Human Tissue Act 2004 and comes from the nominated representative or a person in a qualifying relationship, not from the deceased.

Where a deceased person made no decision in life and appointed no nominated representative, consent comes from the person in the highest-ranking qualifying relationship listed in section 27(4): spouse, civil partner or partner; then parent or child; then brother or sister; then grandparent or grandchild; then niece or nephew; then step-parent; then half-sibling; then friend of long standing. The wife therefore decides. A relative who cannot be contacted or does not wish to decide is passed over, but a relative who actively declines is not. The Act covers England, Wales and Northern Ireland; Scotland has its own Human Tissue (Scotland) Act 2006. The clinical value to the sister does not change the legal position, though counselling should explore why consent is being withheld.

Section 45 makes it an offence to hold bodily material intending to analyse its DNA without qualifying consent, unless the analysis is for an excepted purpose. The excepted purposes in Schedule 4 include medical diagnosis or treatment of the person whose body manufactured the DNA, coroners' functions, crime prevention and court orders; they do not extend to diagnosing or managing a different person such as a relative. Testing a living relative's sample to inform someone else's care therefore needs that relative's consent, and the JCGM recommends that the routine use of stored family samples for quality assurance and relatives' testing is discussed at the time of the original test.

For CPVT and long QT syndrome, the consensus recommends predictive testing of at-risk children from birth onward, because life-threatening events can occur in early childhood and effective preventive treatment (beta-blockade and lifestyle advice) exists. This is the key distinction from HCM, DCM and ACM, where testing is generally recommended from 10–12 years and considered earlier only with early-onset disease in the family. The JCGM principle is the same: testing a child is justified when the result changes the child's own care during childhood.

The ESC 2023 guideline gives cascade testing in paediatric relatives a Class IIa recommendation, to be considered in the light of the underlying cardiomyopathy, the expected age of onset, how the disease has presented in the family, and the clinical and legal consequences of testing a child. The 2022 EHRA consensus recommends predictive testing in HCM from over 10–12 years, and earlier where there is a family history of early-onset disease. ESC Table 12 lists the issues specific to children: autonomy, consent appropriate to understanding, the right to know or not to know, incomplete and age-related penetrance, school and employment, and transition to adult services. There is no UK legal age bar; the decision is a best-interests one made with the family.

Those under 16 are presumed not to have capacity, but an adolescent may be assessed as competent to decide for themselves (Gillick v West Norfolk and Wisbech AHA [1986]) and can then give valid consent. Young people aged 16 or 17 are presumed to have capacity under the Mental Capacity Act 2005. Where a child lacks competence, consent comes from a person with parental responsibility, acting in the child's best interests. In Marfan syndrome a positive result changes childhood care (aortic surveillance and beta-blockade), so testing in childhood is appropriate.

The JCGM 2019 guidance, building on the 2010 British Society for Human Genetics report on testing children, advises that predictive testing for conditions that will only be relevant in adulthood should generally be deferred until the young person can make their own decision, unless an intervention in childhood would change the course of the disease. The child's best interests are the primary justification; benefit to a parent is not. Hereditary ATTR amyloidosis has an onset decades away and no childhood intervention. Parents' requests are best reframed as a discussion about the optimal time to test rather than a refusal.

An adult lacking capacity may have a test carried out if it is in their best interests under section 4, which requires consideration of their past and present wishes, beliefs and values and consultation with carers and others interested in their welfare. Best interests are not confined to clinical benefit; the JCGM (Case 7, a woman with DCM in exactly this situation) notes there is legal precedent for treating testing whose main aim is to help relatives as capable of being in the person's best interests, provided discomfort and distress are weighed, and recommends multidisciplinary discussion. Next of kin have no legal authority to consent for an adult; only a health and welfare attorney or a court-appointed deputy can, and even they must act in best interests.

The first statutory principle is the presumption of capacity. The others are that all practicable steps must be taken to help the person decide, that an unwise decision does not of itself show incapacity, that anything done for a person who lacks capacity must be in their best interests, and that the least restrictive option should be preferred. Capacity is decision-specific and time-specific: the test is whether an impairment of the mind or brain leaves him unable to understand, retain, use or weigh the relevant information, or communicate the decision. A diagnosis of learning disability does not decide the matter, and a parent cannot consent for an adult.

GMC guidance recognises that genetic information about one patient may be relevant to relatives. If the patient refuses to share it, the doctor must balance the duty to make the patient's care their first concern against the duty to help protect others from serious harm; disclosure without consent can be justified where failure to disclose may expose others to a risk of death or serious harm. Unusually, the GMC adds that where practicable the patient's identity should not be disclosed when contacting and advising others about the risks they face. The JCGM frames the familial variant as information confidential to the family rather than to the individual, so the brother can be alerted that the family carries a treatable arrhythmia risk without his sister's clinical details being shared.

The JCGM sets out a sequence: consider whether a breach is necessary at all, since relatives can often be told of a familial risk without revealing in whom the variant was found; if a breach is necessary, attempt to obtain consent, discuss the case with experienced colleagues (for example a clinical ethics committee or the Genethics forum), tell the patient that you intend to disclose and why, contact the relative where practical, keep the disclosure to the minimum needed to communicate risk, and record the balancing carried out and the justification. NHS tracing can identify a relative's GP so that disclosure is mediated by someone the relative knows.

The JCGM regards a disease-causing variant in a family as information confidential to the family rather than to the person in whom it was first found. The molecular details can therefore be shared with the laboratory testing a relative, while the cousin's personal clinical information (her diagnosis, symptoms and results) remains confidential to her. Where a patient has told relatives about a familial risk and a relative then presents, this itself suggests permission, and demanding further verification of consent is usually unnecessary. Good practice is to discuss and document at the original consent that the result may be used for relatives, so that the question does not arise later.

In ABC, the daughter of a man with Huntington's disease sued after she was not told of her risk in time to make her own reproductive decisions. The High Court held that the clinicians owed her a duty of care to balance her interest in being informed against her father's confidentiality, because geneticists routinely acquire reliable information of clinical significance about their patients' relatives. On the facts the balance struck was reasonable, so the duty was not breached and causation was not established. The case does not create a duty to disclose in every situation; it requires the balancing to be carried out and documented, which is exactly what GMC and JCGM guidance already ask for. Every daughter of a man with Fabry disease inherits the variant, so the risk here is certain rather than probabilistic.

Under the Code, insurers will not require or pressure anyone to take a genetic test, and will only ask for a predictive result for conditions approved under the Code and above the financial limits (life £500,000; critical illness £300,000; income protection £30,000 a year). The only approved test is a predictive test for Huntington's disease in life insurance applications over £500,000, so a predictive channelopathy result need not be disclosed. The Code is a voluntary agreement that is a condition of ABI membership, is open-ended and reviewed every three years. Family history can still be asked about and taken into account.

The Code protects predictive genetic tests in people without symptoms. It expressly does not cover diagnostic genetic tests, which confirm or exclude a diagnosis in someone with symptoms, signs or abnormal investigations; those results form part of the medical information an insurer may ask about, in the same way as an echocardiogram. Applicants must take reasonable care not to misrepresent their health under the Consumer Insurance (Disclosure and Representations) Act 2012. The £500,000 threshold relates only to predictive Huntington's disease tests. Counselling before testing should therefore distinguish clearly between a diagnostic test in an affected person and a predictive test in a healthy relative.

Commitment 3 of the Code states that insurers will not ask an applicant to disclose the result of a predictive genetic test of another person, such as a blood relative, nor a result obtained exclusively in research, nor one taken after the policy started. Insurers remain lawfully entitled to ask about family medical history and may price on it. If an applicant volunteers a favourable predictive result, for example a negative test that rules out a risk suggested by the family history, the insurer may use it to offer better terms, but an unfavourable result volunteered by mistake is ignored unless the Huntington's disease exception applies.

From 2001 to 2018 the UK Genetic Testing Network (UKGTN) evaluated and advised on NHS genetic tests. From October 2018 the National Genomic Test Directory, the central feature of the NHS Genomic Medicine Service, took over and now lists every commissioned test with its eligibility criteria, the genes covered and the testing method. The rare and inherited disease directory is reviewed regularly (version 9 covers 2026/27). Inherited cardiac condition indications carry R codes: R127 long QT syndrome, R128 Brugada syndrome, R129 CPVT, R130 short QT syndrome, R131 HCM, R132 DCM and ACM, R133 ACM/ARVC, and R138 for sudden death with a normal post-mortem or idiopathic VF.

The NHS Genomic Medicine Service consolidates NHS genomic testing into a single national network of seven Genomic Laboratory Hubs working to common standards. Each directory indication has an R code with eligibility criteria and named requesting specialties; for Brugada syndrome (R128, a 13-gene panel) these are cardiology and clinical genetics. The directory expects all inherited cardiac condition tests to be performed alongside expert phenotypic assessment in an inherited cardiac conditions clinic, with clinical genetics support, and only where the result is likely to change management for the proband or family.

When a sudden death remains unexplained after autopsy and toxicology, the consensus advises post-mortem genetic testing targeted to channelopathy genes where the circumstances or family history suggest a primary electrical disease; hypothesis-free exome or genome sequencing should not be performed in a decedent or an unexplained cardiac arrest survivor. In England this is the R138 indication (sudden death with a normal post-mortem under 40, or under 60 with a relevant family history), delivered on an inherited cardiac conditions panel using blood or tissue retained at autopsy. Exertional death in a young person raises CPVT and long QT syndrome in particular. Relatives are offered clinical evaluation in parallel, and a pathogenic result then allows targeted cascade testing.

A coroner's post-mortem and the retention of material for the coroner's purposes do not need consent. Once those purposes are complete, however, continued storage or use of the tissue for a scheduled purpose such as genetic testing requires appropriate consent under the Human Tissue Act 2004: from a decision the person made in life, from their nominated representative, or from someone in a qualifying relationship in the section 27(4) order. The Human Tissue Authority notes that continued retention may be in the clinical interests of relatives when a genetic condition is suspected, so the options should be raised with the family before the retention period expires. The ESC gives testing of a deceased person with cardiomyopathy at post-mortem a Class I recommendation when it would help surviving relatives.

A secondary or incidental finding is an actionable result unrelated to the reason for testing and should be handled through the clinical genetics pathway with counselling and clinical assessment, not simply appended to the original report. The JCGM advises that consent for genomic testing should cover the possibility of unexpected findings and how they will be dealt with. The ESC 2023 guideline notes that the American College of Medical Genetics recommends evaluating cardiomyopathy genes for secondary findings whenever broad clinical sequencing is undertaken, but that there is no international consensus and that opportunistic screening of cardiac genes should currently be confined to research. Fabry disease is X-linked, so a confirmed finding has implications for his daughters, mother and sisters; that conversation belongs with him, not directly with relatives.

Pompe disease is autosomal recessive. The ESC 2023 guideline states that when inheritance is clearly other than autosomal dominant, evaluation of relatives should be individualised, and that heterozygous carriers of a clearly recessive cardiomyopathy could be discharged from periodic surveillance. Carriers do not develop the disease, so preventive enzyme replacement has no place. Counselling remains important: a carrier's children are at risk only if the other parent is also a carrier, so partner carrier testing and, where relevant, reproductive options should be discussed with a genetics professional.

The ESC gives a Class IIa recommendation to discussing reproductive genetic testing options with all families who have a genetic diagnosis, and a Class I recommendation that counselling on the risk of inheritance is offered to all men and women before conception. Options include preimplantation genetic testing for a monogenic disorder (PGT-M) after IVF, which in the UK is regulated by the Human Fertilisation and Embryology Authority and licensed for conditions with high penetrance and significant morbidity, and prenatal diagnosis by chorionic villus sampling from 10–14 weeks or amniocentesis after 15 weeks. If prenatal testing is chosen it should be done early enough in the pregnancy to allow decisions about continuation or planning of delivery (Class I). Counselling must be non-directive; nothing is required.

Interpretation of a genetic result can change in either direction as evidence accumulates, so the ESC 2023 guideline states that systematic reclassification and communication back to families is crucial, and the 2024 AHA/ACC HCM guideline makes serial re-evaluation of variant significance a Class 1 recommendation. An upgrade to likely pathogenic enables targeted cascade testing that was previously impossible and can reopen a family. The JCGM advises that consent conversations should explain that interpretation may be updated and that the patient may be recontacted, while not promising automatic recontact unless the service has a reliable mechanism; patients with uncertain findings should be encouraged to seek an updated interpretation periodically.

The 2022 EHRA consensus notes that several companies offer direct-to-consumer sequencing that includes inherited cardiac genes in people without symptoms, and that the benefits and harms of this have not been established. A consumer result is a prompt for referral, not a diagnosis: the ESC 2023 guideline requires that genetic testing is performed with access to a multidisciplinary team with expertise in variant interpretation (Class I), and cascade testing depends on a confirmed pathogenic variant that fits the clinical context. Confirmation in an NHS Genomic Laboratory Hub, pre- and post-test counselling, and assessment for cardiac amyloidosis come first; disease-modifying therapy is for established amyloid cardiomyopathy, not for carriers.

Danon disease is X-linked. A man passes his X chromosome to every daughter and his Y chromosome to every son, so all daughters inherit the LAMP2 variant and no sons do. Because LAMP2 loss behaves as X-linked dominant, heterozygous daughters are at risk of cardiomyopathy, typically presenting later and less severely than males. A 50% risk to each child applies to autosomal dominant conditions, and 25% to autosomal recessive ones. Counselling on the risk of inheritance before starting a family is a Class I recommendation in the ESC cardiomyopathy guideline.

Evaluation of familial inheritance with a three-generation family history is a Class 1 recommendation, and the 2023 ESC guideline lists obtaining a three-generation pedigree among the core tasks of genetic counselling. The pedigree identifies the most clearly affected person to test first, shows whether disease is familial, and defines which relatives are at risk whatever the genetic result. Sudden deaths, unexplained drownings and road accidents, and diagnoses in relatives should be asked about explicitly. Testing begins with the proband; broad testing of unaffected relatives before the proband is avoided.