Arrhythmogenic Cardiomyopathy

Meet the patient

A 19-year-old rower slumps over the finish line unconscious, and comes round in the ambulance with an ECG showing T-wave inversion across V1 to V3 and a tiny notch riding the end of his QRS. He has palpitated through training for six months, always in the last kilometre, and an uncle died suddenly at 41 playing football. The registrar calls it benign RVOT ectopy and reaches for reassurance.[1][4]

Two exam questions are now live, and the second is the one that buries patients: is this ARVC or benign RVOT VT? (the axis and the QRS settle it in thirty seconds) and may he go back in the boat? (no — not until arrhythmogenic cardiomyopathy is excluded). Hold those two questions and everything below slots into place.[1][6]

The one spectrum, three faces — and why ARVC grew into ACM

Arrhythmogenic cardiomyopathy is an inherited heart-muscle disease in which ventricular myocardium is progressively replaced by fibro-fatty scar — classically in the right ventricle, but increasingly in the left, and often both. It used to be called arrhythmogenic right ventricular cardiomyopathy (ARVC); the umbrella widened to ACM once it became clear the left ventricle is involved in over half of cases.[1][5]

Four pillars hold the disease up, and examiners want them named in order: a genetic substrate (usually autosomal-dominant desmosomal mutation); a structural phenotype of fibro-fatty substitution beginning at the RV inflow, outflow and apex; an electrical phenotype of slow conduction — epsilon waves, late potentials, re-entrant VT; and a clinical phenotype of palpitations, syncope and sudden death in the young, almost always exertion-related.[1][8]

The criteria have tightened with the science: the 1994 ESC Task Force gave way to the quantitative 2010 Modified Task Force Criteria (Marcus), then to the 2020 Padua CMR criteria (Corrado) that finally let the MRI carry its weight.[3]

The triangle of dysplasia — why the right ventricle takes the beating

The right ventricle is preferentially scarred because it is the thinnest-walled chamber under the highest wall stress when you exercise. Repeat that sentence in a viva and you have earned the mechanism marks.[1]

The disease homes in on three regions — the RV inflow, the RV outflow tract, and the RV apex — the triangle of dysplasia, where wall stress is highest and the myocardium shears apart first under load. Endurance sport is not a bystander here: it is the loading condition that detonates the genotype, which is exactly why a marathon multiplies arrhythmic risk around five-fold in a carrier.[1][6]

Etymology for viva gold: dysplasia, from Greek dys (bad) plus plasis (formation) — badly formed. The name predates the genetic era; the original Italian pathologists saw a ventricle that looked malformed, fatty and thin, and the word survived the discovery that the malformation is acquired, gene by gene, year by year.[8]

Three faces on imaging, one family of genes

Classify ACM along three axes — phenotype, genotype, and phase — and never blur them. The first axis is which ventricle is scarred.[1]

[1]

The second axis is genotype — and this is the cluster to memorise. Desmosomal genes account for roughly half to two-thirds of index cases; the rest are non-desmosomal.[1]

The desmosomal cluster, in descending yield: PKP2 (plakophilin-2) — the single commonest, around 40 percent of familial ARVC, almost always truncating variants; DSP (desmoplakin) — left-dominant and biventricular forms, and the gene behind exercise-triggered myocarditis; DSG2 (desmoglein-2) and DSC2 (desmocollin-2) — perhaps 5 to 10 percent each; and JUP (plakoglobin) — recessive, and the cause of Naxos disease.[8][9]

Two named syndromes travel with this cluster and examiners love them: Naxos disease — recessive JUP, the triad of woolly hair, palmoplantar keratoderma and ARVC with near-complete penetrance by adolescence; and Carvajal syndrome — recessive DSP, the same skin-and-hair triad but with left-dominant cardiomyopathy.[8]

The classic trap — the genotypes that kill with a preserved EF. LMNA, DSP, PLN and TMEM43 carry sudden-death risk that the ejection fraction under-represents; the ESC 2022 guideline therefore permits an ICD at LVEF above 35 percent when these genotypes carry high-risk features. The EF is a lagging indicator here, and waiting for it to fall is how patients die.[2]

The non-desmosomal tail: TMEM43 (Newfoundland founder, near-lethal in untreated males), LMNA (overlap with DCM and conduction disease), PLN p.Arg14del (Netherlands and Spain founder, biventricular with mid-wall LV scar), plus DES, CDH2, CTNNA3, SCN5A, TTN and RBM20. Compound and digenic heterozygosity — two hits in the same or paired desmosomal genes — produces earlier onset and a more savage phenotype, which is why severity clusters within a family.[9][10]

The four phases — concealed, electrical, failing, burnt-out

ACM moves through four named phases, and a patient can die in any of them — including the first. This is the phase rule examiners want reproduced.[1]

1. Concealed phase — silent structural change, normal tests, no symptoms; the first presentation may be sudden cardiac death on the track.
2. Overt electrical phase — palpitations, syncope, non-sustained or sustained VT, almost always exertion-triggered.
3. RV dysfunction phase — right-heart failure with raised JVP, oedema, hepatomegaly.
4. Biventricular burnt-out phase — indistinguishable from dilated cardiomyopathy, both ventricles failing, arrhythmias refractory.[1]

How common, who, and how lethal

[1] [4]

ACM accounts for roughly 5 percent of sudden cardiac death in the under-35s in the United States — but for over 20 percent of athletic sudden death in the Veneto region of Italy, a founder-effect, high-penetrance belt where the disease was first mapped. The geography is exam gold.[4][6]

Risk accelerators to name on autopilot: male sex (3 to 1 in overt disease — partly biological, partly because men compete harder), competitive endurance sport (marathon, cycling, rowing, swimming — the five-fold multiplier), family history of SCD under 50, and Mediterranean or founder ancestry (Veneto, Naxos, the Dutch PLN cluster, Newfoundland, South Africa).[4][6]

Why the scar forms — the wounded-healer hypothesis

The unifying model is the wounded healer: a mechanically weak desmosome tears under load, the dying myocytes are replaced by fat and fibrous tissue, and that scar both conducts slowly and re-enters. Five steps, each with a clinical fingerprint.[8]

Step 1 — a defective desmosome. A mutation in PKP2, DSP, DSG2, DSC2 or JUP weakens the intercalated disc. Desmosomes anchor desmin filaments to the cadherins (desmoglein, desmocollin) through plakoglobin and plakophilin, and bolt them to the cytoskeleton through desmoplakin. Break any link and the junction turns friable.[1]

Step 2 — exercise shears the myocytes apart. The thin-walled, high-stress right ventricle takes the load; repetitive stretch during endurance sport detaches cardiomyocytes, fastest at the triangle of dysplasia. This is the mechanistic reason sport is not a lifestyle choice here, it is a disease accelerator.[1]

Step 3 — death and inflammatory repair. Detached myocytes die by apoptosis and necrosis. A macrophage infiltrate clears the debris — often misread histologically as myocarditis — and the gap is patched with fibroblasts and, characteristically, adipocytes.[1][10]

Step 4 — fat, through Hippo and Wnt. Desmosomal dysfunction shunts plakoglobin out of the junction and into the nucleus, where it suppresses canonical Wnt signalling and fires up the Hippo effector YAP/TAZ, diverting cardiac progenitors toward fat. That is the histological signature — surviving myocyte strands swimming in fat.[8]

Step 5 — slow conduction and re-entry. The fibro-fatty scar insulates surviving muscle, conducting slowly and fractionally — the surface epsilon wave and the late potentials on signal-averaged ECG. Slow conduction plus unidirectional block is the substrate for re-entrant VT, with a macro-re-entrant circuit around RV scar exiting near the apex or inflow — the classical LBBB VT with a superior axis.[1]

How the patient walks in — and the trap of the normal examination

The presentation tracks the four phases and is wildly variable, even within one family. A normal examination does not exclude ACM — the diagnosis is driven by the ECG and imaging, not the stethoscope.[1][4]

Palpitations are the commonest symptom, roughly a third to a half of patients; they may be isolated PVCs, NSVT, or sustained VT. Syncope or pre-syncope that is exertion-related presages sudden death and mandates urgent evaluation — do not file it as vasovagal. Sudden cardiac arrest is the first presentation in perhaps 5 to 10 percent, often during or just after exercise. In the burnt-out phase, right-heart failure dominates — oedema, raised JVP, hepatomegaly, effort intolerance.[1]

The classic trap — a normal exam in early disease. Between events the patient looks and sounds well. Auscultation only turns abnormal late (an S3, a wide fixed-split S2, tricuspid regurgitation in RV failure). The dermatological phenotypes are the exception: Naxos brings woolly hair and palmoplantar keratoderma, Carvajal the striate keratoderma — spot the skin and you have the genotype.[1]

The symptom that decides the work-up is exertion. An athlete with palpitations or syncope during sport is assumed to harbour ACM, HCM, long QT, an anomalous coronary or myocarditis until proven otherwise. The trigger is the clue, not the symptom.[6]

Read the ECG like the consultant does — EPSILON, with a scene

The ECG is the cornerstone of diagnosis, and the findings cluster into one memorable signature. Picture the consultant turning to the board after the arrest: she writes seven letters and says if you cannot rule ARVC in or out with this, you have not looked hard enough.[1]

The high-yield findings, then the mnemonic:[1]

• Epsilon wave — a low-amplitude blip riding the end of the QRS, best in V1 to V3; pathognomonic, but only there in about a third of overt cases.
• T-wave inversion V1 to V3 without complete RBBB — the single commonest repolarisation abnormality (half to four-fifths of overt disease), and a major Task Force criterion in anyone over 14 years.
• Prolonged S-wave upstroke — at least 55 ms in V1 to V3, even without a frank epsilon wave.
• Localised QRS prolongation in V1 to V3 with a relatively normal V6 (the parietal block).
• Terminal activation delay — at least 55 ms from the S-wave nadir to the QRS end in V1 to V3.
• Low limb-lead voltages in advanced disease; frequent PVCs of LBBB morphology with superior axis, NSVT or sustained VT.
• Late potentials on signal-averaged ECG — filtered QRS over 114 ms, RMS40 under 20 microV, LAS over 38 ms — a minor Task Force criterion.[1]

[1]

The scene that fixes the mnemonic: epsilon wave on the strip, prolonged S-upstroke in V1, superior-axis VT on the monitor, inverted T waves across the precordial leads, late potentials on the signal-averaged ECG, an idiopathic label you have now refused, the triangle of dysplasia on the MRI, and no RBBB to explain any of it. Seven findings, one disease.[1]

Two ECG subtleties examiners test: incomplete or complete RBBB is common and does not exclude ACM (TWI extending into V4 to V6 still points to it), and TWI in V1 to V3 in a child under 14 years may be a normal juvenile pattern — do not over-diagnose ACM before adolescence unless other criteria are present.[1]

The 30-second bedside fork — ARVC VT or benign RVOT VT?

This is the single most decisive bedside discriminator in the topic, and it is decided by the axis and the QRS. Get it wrong and you reassure a patient who is about to die, or you implant a defibrillator in someone who needed an ablation and a cup of tea.[1]

[1]

The discriminator line: superior axis plus notched QRS plus scar on the MRI equals ARVC; inferior axis plus smooth QRS plus adenosine-sensitive equals benign RVOT VT. One sentence, full marks.[1]

The wider differential — and the mimics that also scar the RV

Several diseases produce VT, syncope and an abnormal RV, and each carries a different management. Name them with a discriminator, not a list.[2]

[1]

The classic trap — recurrent viral myocarditis that is actually DSP

When one patient keeps presenting with exertion-triggered, troponin-positive chest pain and patchy late gadolinium enhancement, it is not bad luck with viruses — it is desmoplakin. Poller and colleagues showed that truncating DSP variants cause familial recurrent exercise-triggered myocarditis that masquerades as viral illness, and the clue to stop calling it myocarditis and start calling it genetics is a family history of sudden death or dilated cardiomyopathy.[10]

The same trap runs the other way: the older patient labelled idiopathic dilated cardiomyopathy may be a burnt-out ARVC — a prior history of palpitations or syncope, RV predominance, and an epsilon wave redirect the diagnosis and the family screen.[5]

Make the diagnosis with the 2010 Task Force math (and the Padua numbers)

The diagnostic strategy is the 2010 Modified Task Force Criteria in six categories — and the arithmetic is the exam favourite. A definite diagnosis needs two major, or one major plus two minor, or four minor from different categories; borderline is one major plus one minor (or one major, or two to three minor); possible is a single minor.[1]

The six categories, with the thresholds that score marks:[1]

1. Imaging (global or regional dysfunction). Echo major: RVOT PLAX at least 32 mm or PSAX at least 36 mm, or fractional area change 33 percent or below; LV-dominant major is regional akinesia with LVEF 35 to 53 percent. CMR (Padua 2020) major: RVEF 40 percent or below with RVEDVi at least 110 mL/m² in men or at least 100 mL/m² in women; LVEF 45 percent or below with LVEDVi at least 95 mL/m² (men) or 80 mL/m² (women).[3]
2. Tissue characterisation (biopsy). Residual myocytes below 60 percent by morphometry is major; 60 to 75 percent is minor. Biopsy the septum — the free wall risks perforation — and histology shows fibro-fatty replacement with surviving myocyte strands, pathognomonic.[1]
3. Repolarisation. Major: TWI V1 to V3 or beyond, without complete RBBB, in anyone over 14 years. Minor: TWI V1 to V2, TWI V4 to V6 (left-dominant), or TWI V1 to V4 with complete RBBB.[1]
4. Depolarisation or conduction. Major: epsilon wave. Minor: late potentials on SAECG; terminal activation duration at least 55 ms in V1 to V3; V1 to V3 over V6 QRS ratio at least 1.2.[1]
5. Arrhythmia. Major: sustained or non-sustained VT of LBBB morphology with superior axis. Minor: LBBB VT with inferior axis; frequent PVCs of LBBB morphology (over 500 in 24 hours on Holter); atrial fibrillation or flutter in advanced disease.[1]
6. Family history. Major: ACM in a first-degree relative, or a pathogenic mutation, or pathological autopsy in a first-degree relative. Minor: premature SCD under 35 years in a first-degree relative; definite ACM in a second-degree relative.[1]

[1]

The Padua 2020 numbers worth memorising verbatim: RVEF 40 percent or below with RVEDVi at least 110 mL/m² (men) or at least 100 mL/m² (women) is a major criterion — and isolated subepicardial or mid-wall LGE, dropped from the 2010 TFC, returns in Padua as a strong arrhythmia predictor. Note the LGE pattern: subepicardial or mid-wall, never subendocardial — subendocardial is ischaemic until proven otherwise.[3]

Investigations that change management

A handful of tests do the diagnostic work; everything else is context. First-line is the 12-lead ECG plus signal-averaged ECG, a 24-hour Holter (extended if suspicion is high), and a transthoracic echocardiogram, then cardiac MRI with the Padua quantification as the tissue gold standard.[1]

The Holter quantifies PVC burden — over 1,000 PVCs in 24 hours is a minor Task Force criterion, over 10,000 is high-risk — and captures the VT morphology. Exercise ECG is used cautiously because ACM arrhythmias are exertion-triggered; it may unmask TWI or VT in recovery, so do not run it in overt disease without monitoring.[1]

Genetic testing is both a diagnostic and a public-health tool: a pathogenic variant is itself a major Task Force criterion and triggers cascade screening of every first-degree relative with ECG, Holter, echo and CMR. High-sensitivity troponin and NT-proBNP track disease extent. The electrophysiological study is no longer routine — the Cadrin-Tourigny arrhythmia risk model does the job with NSVT, genotype and CMR features instead.[7]

Management — no sport, beta-blocker first, ICD when it counts

Four parallel streams — lifestyle, drugs, devices, ablation or surgery — and the lifestyle line is the one juniors under-prescribe. Hold the streams in that order.[2]

[1]

The time-critical scenario first: monomorphic or polymorphic VT with haemodynamic compromise in a young person. Run the ALS pathway — ABCDE, high-flow oxygen only if hypoxic, correct potassium above 4.0 mmol/L and magnesium above 2.0 mg/dL, and treat the triggers (ischaemia, fever, electrolytes, pro-arrhythmic drugs, sympathomimetics). Pulseless VT or VF: immediate defibrillation at 200 J biphasic with CPR, amiodarone 300 mg IV after the third shock then 900 mg per 24 hours, adrenaline 1 mg IV every 3 to 5 minutes once defibrillation has failed. Stable monomorphic VT: amiodarone 150 to 300 mg IV over 10 to 20 minutes (or procainamide); unstable VT: synchronised DC cardioversion under sedation. Once stabilised, plan an ICD — these patients recur.[1]

1. Lifestyle — the most under-prescribed intervention. All competitive and endurance sport is prohibited in definite ACM (Bethesda 36, 2020 IOC, ESC 2021 — absolute). The risk of sudden death during sport is multiplied about five-fold, and the disease itself progresses faster under load.[6]

Recreational low-intensity activity (gentle walking, golf) is permitted in carriers without phenotype; high-intensity isometric weightlifting is not. Occupational restrictions hit commercial pilots, drivers, divers and HGV licences.[1]

The classic trap — the sport that kills

The single most preventable cause of sudden death in ACM is the sport the patient is still playing. Everyone remembers the beta-blocker and forgets the lifestyle line; that is the recurring trainee error, and it is the one that costs lives. Corrado showed athletic sudden death from ARVC fell in Veneto once Italy introduced mandatory ECG screening of athletes and disqualified the affected — screening works precisely because disqualification works.[6]

2. Pharmacological therapy. Beta-blockers are first-line to suppress adrenergically triggered arrhythmia and reduce RV wall stress:[1]

• Sotalol — historically most effective in ARVC; start 80 to 160 mg orally twice daily, renal dosing, QTc monitoring, avoid in severe LV dysfunction.
• Metoprolol succinate 23.75 to 190 mg orally daily, or bisoprolol 1.25 to 10 mg orally daily — first-line when sotalol is not tolerated.
• Carvedilol 3.125 to 25 mg orally twice daily — preferred when LV dysfunction coexists.[1]
• Amiodarone 100 to 200 mg orally daily (after loading 800 to 1600 mg per day for 1 to 3 weeks) — reserved for sotalol failure; monitor TFTs, LFTs, lung function and QTc.
• Mexiletine 200 mg orally three times daily — may help sodium-channel-positive genotypes; flecainide carries pro-arrhythmic risk.[1]

In the burnt-out phase, treat heart failure exactly as dilated cardiomyopathy — ACE inhibitor or ARB or ARNI, beta-blocker, MRA, SGLT2 inhibitor, diuretics for congestion, and CHA2DS2-VASc-based anticoagulation for atrial fibrillation. Avoid QT-prolonging drugs (macrolides, fluoroquinolones, ondansetron, methadone) in patients on sotalol or amiodarone.[1]

3. Implantable cardioverter-defibrillator — the only therapy proven to reduce sudden death. Indications follow the 2022 ESC framework:[2]

• Class I (mandatory): survivors of sudden cardiac death from VT or VF; sustained VT with structural disease.
• Class IIa: unexplained syncope with structural disease; NSVT on Holter with inducible VT on EPS (though the role of EPS is declining — many centres now offer an ICD on extensive scar or multiple risk factors alone).
• Class IIb: severe RV or LV systolic dysfunction (LVEF 35 percent or below); LMNA, DSP, PLN or TMEM43 carriers with high-risk features — ICD at LVEF above 35 percent, because sudden-death risk is high even with a preserved EF.
• Class III: asymptomatic gene carriers without phenotype — surveillance, not device.[1]

Device specifics for ACM: transvenous leads may fail in advanced RV disease (poor sensing, perforation of the thinned free wall), so the subcutaneous ICD (S-ICD) is increasingly preferred where VT is monomorphic and painless anti-tachycardia pacing is not needed; epicardial leads serve those who fail transvenous.[1]

The named trap — ablation feels like a cure, and it is not

Catheter ablation reduces ICD shocks; it does not prevent sudden death. Everyone reaches for ablation after the first storm and thinks the problem is solved — it is not, and the ICD stays in. ARVC VT is macro-re-entrant with a critical isthmus on the epicardial RV surface, so epicardial ablation is usually required and superior to endocardial-only; recurrence is common (half to two-thirds within three years) because the disease progresses. Do coronary angiography before epicardial ablation to avoid arterial injury.[1]

Advanced therapy for refractory disease: cardiac sympathetic denervation for VT storm; heart transplantation for refractory heart failure or intractable VT storm in the burnt-out phase (survival excellent, arrhythmia-free post-transplant); LVAD as a bridge.[1]

Subtypes and scenarios you will meet

• Classic RV-dominant (ARVC) — the textbook phenotype; PKP2 in about 40 percent; beta-blocker plus ICD if high-risk plus no sport.[1]
• Left-dominant ACM — subepicardial or mid-wall LV scar, lateral TWI, often DSP, LMNA, PLN, DSG2; no epsilon wave (LV scar does not slow RV activation); lower ICD threshold in LMNA and DSP even with preserved LVEF.[5]
• Naxos disease (recessive JUP) — woolly hair, palmoplantar keratoderma, near-complete ARVC penetrance by adolescence; ICD is standard.[8]
• Carvajal syndrome (recessive DSP) — striate keratoderma and woolly hair with left-dominant ACM.
• Familial exercise-triggered myocarditis (DSP) — recurrent troponin-positive chest pain with patchy LGE; genetic cascade is the key to escaping the viral myocarditis label.[10]
• ACM in the athlete — pre-participation ECG detects TWI V1 to V3 and LBBB PVCs; definite ACM means lifetime disqualification; Corrado 2003 showed athletic ARVC sudden death fell in Veneto after mandatory screening.[6]
• LMNA-associated ACM — high sudden-death risk at preserved LVEF; ESC 2022 advises an ICD above 35 percent with NSVT, male sex or a non-missense variant.[2]
• TMEM43 p.S358L (Newfoundland) — near-universal male penetrance; prophylactic ICD from age 18 recommended.[2]

Complications and the pitfalls that lose marks

• Sudden cardiac death — the dominant mode of death in the young, exertion-related.
• Recurrent monomorphic VT, VT storm, appropriate ICD shocks — the commonest sustained arrhythmia; ablation reduces shock burden.
• Inappropriate ICD shocks — atrial fibrillation or SVT with aberrancy, or T-wave oversensing; programming and beta-blockade help.
• Right-heart failure then biventricular failure in the burnt-out phase; atrial fibrillation (anticoagulate by CHA2DS2-VASc).
• Device complications — lead perforation of the thinned RV free wall, infection, pneumothorax; favour S-ICD.
• RV thrombus and pulmonary embolism — scarred RV aneurysms are thrombogenic; consider anticoagulation in RV akinesia with low flow.[1]

The pitfalls examiners reach for: mislabelling ARVC VT as benign RVOT VT (check the axis and the QRS); missing TWI V1 to V3 in an athlete over 14 (dismissed as early repolarisation); failing to screen the family (about 30 percent of sporadic cases have an affected relative); letting the patient return to competitive sport; misdiagnosing DSP myocarditis as viral; placing a transvenous lead in a paper-thin RV (consider S-ICD); treating the arrhythmia but not the heart failure; accepting a single normal ECG or MRI in a gene carrier (penetrance evolves — re-test every 1 to 2 years).[1][10]

Prognosis, disposition, and the relatives you must screen

Annual sudden-death risk in definite ACM is about 2.5 to 3 percent untreated; ICD therapy reduces it substantially. The Cadrin-Tourigny and Padua risk models integrate sustained VT, aborted SCD, syncope, young age, male sex, severe RV or LV dysfunction, extensive LGE, high NSVT burden and high-risk genotype into an annual arrhythmic probability — an annual risk above 5 to 10 percent generally supports a primary-prevention ICD.[4][7]

Disposition: low-risk gene carriers get annual ECG, Holter and echo with CMR every 2 to 3 years; all definite ACM belongs in a specialist inherited cardiac conditions clinic with a cardiology-and-genetics MDT. Driving and occupational advice matter — a group 2 licence (HGV or PCV) is forfeited, private driving restricted after ICD, syncope or VT. Pregnancy is generally well tolerated in stable disease; switch teratogenic drugs and re-image at six months because penetrance may worsen postpartum.[1]

Evidence and guidelines that score marks

• Marcus 2010 (Modified Task Force Criteria, Circulation) — the quantitative redefinition of the 1994 criteria; six categories; the international diagnostic standard.[1]
• Corrado 2020 (Padua criteria, International Journal of Cardiology) — quantitative CMR thresholds for RV and LV volumes; integrated into ESC 2022.[3]
• ESC 2022 Ventricular Arrhythmia and SCD Guideline (Zeppenfeld) — the current European standard for risk stratification and ICD thresholds, with genotype-specific advice for LMNA, DSP, PLN, TMEM43.[2]
• Sen-Chowdhry 2008 (JACC) — defined left-dominant ACM as a distinct entity; shifted the umbrella from ARVC to ACM.[5]
• Marcus 2009 (North American Multidisciplinary Study, Heart Rhythm) — clinical presentation and diagnostic evaluation in a large cohort.[4]
• Corrado 2003 (JACC) — sports activity and the risk of sudden death in the young; the evidence behind mandatory ECG screening and disqualification.[6]
• Marcus 2006 (Circulation) — the mechanistic explanation, from observation to the desmosomal hypothesis.[8]
• Xu 2010 (JACC) — compound and digenic heterozygosity contributes to ARVC, explaining intra-family variability.[9]
• Cadrin-Tourigny 2019 (Eur Heart J) — the predictive risk model for ventricular arrhythmias in mutation carriers.[7]
• Poller 2020 (J Am Heart Assoc) — DSP truncating variants cause familial recurrent exercise-triggered myocarditis masquerading as viral.[10]

The mantra

Epsilon wave and TWI V1 to V3, superior-axis LBBB VT, no competitive sport, beta-blocker first, ICD is the only thing that stops sudden death.[1][2]

Ward-round test — three stems, thirty seconds each

Stem 1 — the rower who collapses at the finish line (answer)

A 19-year-old rower syncopes during a race. The ECG shows T-wave inversion V1 to V3 and frequent LBBB PVCs. The registrar calls it benign and wants to clear him to play. What do you do? Model: Do not clear him. Exertional syncope with TWI V1 to V3 and LBBB ectopy in a young athlete is arrhythmogenic cardiomyopathy until proven otherwise — alongside HCM, long QT, anomalous coronary and myocarditis. Stand him down from competitive sport immediately and work him up with signal-averaged ECG, 24-hour Holter, transthoracic echo and cardiac MRI under the Padua criteria, plus a family history of SCD under 50 and genetic cascade screening. Only when the 2010 Task Force math and the MRI exclude ACM may he return — and a definite diagnosis means lifetime disqualification.[1][6]

Stem 2 — recurrent monomorphic VT, LBBB, superior axis (answer)

A 26-year-old presents with recurrent monomorphic VT. The VT is LBBB morphology with a superior axis (negative in II, III, aVF) and a notched, slurred QRS. Adenosine does not terminate it. Benign RVOT VT or ARVC? Model: This is ARVC, not benign RVOT VT — and the discriminator is the axis. Superior axis (negative in the inferior leads) with a notched, slurred QRS that is adenosine-insensitive points to a scar-related macro-re-entrant circuit exiting from the RV inflow or apex; benign RVOT VT is focal, has an inferior axis, a smooth rapid QRS, and terminates with adenosine. Confirm with CMR (Padua criteria — RV akinesia or aneurysm, subepicardial or mid-wall LGE) and genetic testing; start a beta-blocker, restrict sport, and risk-stratify for an ICD.[1]

Stem 3 — the family where viral myocarditis keeps recurring (answer)

A 23-year-old has had three admissions in two years for troponin-positive chest pain after exercise, each labelled viral myocarditis, with patchy subepicardial late gadolinium enhancement on CMR. Her father died of dilated cardiomyopathy at 45. What is the diagnosis, and what do you do? Model: This is DSP-related arrhythmogenic cardiomyopathy presenting as familial recurrent exercise-triggered myocarditis (Poller 2020) — not recurrent viral illness. The clue is the combination of exertional triggering, patchy non-ischaemic LGE, and a family history of DCM or sudden death. Cascade to desmosomal genetic testing; if a DSP truncating variant is found, screen every first-degree relative with ECG, Holter, echo and CMR, restrict competitive sport, and risk-stratify for an ICD — DSP is a high-risk genotype that warrants an ICD even above an LVEF of 35 percent.[10]

References

1. [1]Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria Circulation, 2010.PMID 20172911
2. [2]Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death Eur Heart J, 2022.PMID 36017572
3. [3]Corrado D, Perazzolo Marra M, Zorzi A, et al. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria Int J Cardiol, 2020.PMID 32561223
4. [4]Marcus FI, Zareba W, Calkins H, et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: results from the North American Multidisciplinary Study Heart Rhythm, 2009.PMID 19560088
5. [5]Sen-Chowdhry S, Syrris P, Prasad SK, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity J Am Coll Cardiol, 2008.PMID 19095136
6. [6]Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol, 2003.PMID 14662259
7. [7]Cadrin-Tourigny J, Bosman LP, Nozza A, et al. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy Eur Heart J, 2019.PMID 30915475
8. [8]Marcus F, Towbin JA The mystery of arrhythmogenic right ventricular dysplasia/cardiomyopathy: from observation to mechanistic explanation Circulation, 2006.PMID 17060394
9. [9]Xu T, Yang Z, Vatta M, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy J Am Coll Cardiol, 2010.PMID 20152563
10. [10]Poller W, Haas J, Klingel K, et al. Familial Recurrent Myocarditis Triggered by Exercise in Patients With a Truncating Variant of the Desmoplakin Gene J Am Heart Assoc, 2020.PMID 32410525