Cardiomyopathies — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr Liam Cooper, 24 years old, semi-professional cricketer. [1]

Presenting complaint: Referred by his general practitioner after a routine screening echocardiogram was performed following the sudden death of his older brother, Sean, age 27, who collapsed during a match nine weeks ago and could not be resuscitated. Liam is currently asymptomatic — no chest pain, no exertional dyspnoea, no palpitations, no syncope. He trains six days a week. [1]

Past history: Asthma, well-controlled with a salbutamol inhaler. No prior cardiac symptoms. No medication use beyond the inhaler. He does not smoke, drinks alcohol socially, and has never used performance-enhancing drugs or recreational substances. [1]

Family history:

• Brother Sean — died suddenly at 27 during cricket; autopsy showed hypertrophic cardiomyopathy
• Father — hypertrophic cardiomyopathy, alive at 54, has an implantable cardioverter-defibrillator implanted at age 41 after a run of non-sustained ventricular tachycardia
• Paternal grandfather — died suddenly at 49, cause recorded as a heart attack
• Mother and younger sister — well, no cardiac history [1]

Examination findings (trainee elicits):

• Comfortable, athletic build, no distress
• Pulse 58 beats per minute, regular, jerky upstroke
• Blood pressure 132 over 78, normal pulse pressure
• Bifid apex beat in the 4th intercostal space at the mid-clavicular line
• Systolic thrill at the lower left sternal edge
• Ejection systolic murmur, grade 3 out of 6, at the lower left sternal edge, increasing on Valsalva and standing, decreasing on squatting and handgrip
• No diastolic murmur, normal second heart sound
• Lungs clear, JVP not elevated, no peripheral oedema [1]

Investigations:

• ECG: sinus rhythm with left ventricular hypertrophy by voltage criteria, deep T-wave inversions in leads I, aVL, and V4 to V6, and deep septal Q waves in the inferior and lateral leads
• Echocardiogram: asymmetrical septal hypertrophy, maximal wall thickness 22 mm, LVOT gradient 35 mmHg at rest increasing to 75 mmHg with Valsalva, systolic anterior motion of the mitral valve, preserved ejection fraction 65 per cent
• Cardiac MRI: maximal wall thickness 23 mm at the basal septum, late gadolinium enhancement at the right ventricular insertion points and patchy within the hypertrophied septum, covering approximately 15 per cent of LV mass
• 48-hour Holter: four runs of non-sustained ventricular tachycardia, longest 8 beats at 150 beats per minute
• Exercise test: achieved 12 METS, blood pressure rose from 132 over 78 to 168 over 84 — a normal haemodynamic response
• HCM Risk-SCD calculator: 5-year estimated risk 5.2 per cent (intermediate risk) [1]

Candidate's structured presentation (model)

Opening statement: [1]

"Mr Cooper is a 24-year-old asymptomatic semi-professional cricketer referred after his brother died suddenly from hypertrophic cardiomyopathy. His own evaluation confirms the diagnosis of hypertrophic cardiomyopathy: asymmetrical septal hypertrophy with a maximal wall thickness of 22 mm, dynamic LVOT obstruction with a provocable gradient of 75 mmHg, systolic anterior motion, and a characteristic bifid apex and dynamic murmur. His cardiac MRI shows patchy late gadolinium enhancement, his Holter captured four runs of non-sustained ventricular tachycardia, and his HCM Risk-SCD score is 5.2 per cent at five years — intermediate risk. [1]

His problems are:

1. Hypertrophic cardiomyopathy, obstructive — confirmed, with a maximal wall thickness of 22 mm and dynamic LVOT obstruction
2. A striking family history of sudden cardiac death — his brother at 27, his father with an ICD, his paternal grandfather dead at 49
3. Intermediate sudden cardiac death risk — HCM Risk-SCD 5.2 per cent, with the additional markers of NSVT and a positive family history
4. The ICD decision — the central and genuinely contested question in this case
5. Exercise and competitive sport — he is an athlete, and HCM is the leading cause of sudden death in young athletes
6. Family screening and genetic testing — cascade evaluation of his surviving relatives [1]

My immediate priority is to make a defensible ICD decision, address the exercise restriction, and initiate family screening. The intermediate risk score means this is a shared decision, not an automatic recommendation — and the examiners will expect me to reason through both sides." [1]

Key management discussion — the ICD decision: [1]

"This is an intermediate-risk case and I will present the reasoning explicitly to the patient. The HCM Risk-SCD calculator returns 5.2 per cent at five years, which falls in the 4 to under 6 per cent band where an ICD may be considered — not the 6 per cent or above band where it should be considered. [1]

Arguments FOR an ICD: he has multiple established major risk factors independent of the calculator — a family history of sudden death in a first-degree relative (his brother) under 50, and non-sustained VT on Holter. The 2020 AHA and ACC guideline major-risk-factor approach considers either of these sufficient to support ICD discussion, and he has both. The extensive late gadolinium enhancement on his MRI, covering 15 per cent of LV mass, is an emerging prognostic marker that, while not in the original calculator, is incorporated into modern risk thinking and supports proceeding. He is young with a long expected exposure to arrhythmic risk. His brother's death is the exact event the ICD is designed to prevent. [1]

Arguments AGAINST an automatic ICD: his maximal wall thickness is 22 mm, well below the 30 mm threshold for massive LVH. His exercise blood pressure response is normal. His risk score is intermediate, not high. ICDs carry real morbidity — a younger patient has decades of lead and battery revisions ahead, with cumulative infection and lead-failure risk, and inappropriate shock rates of 5 to 10 per cent per year in young active patients, often from atrial arrhythmias or oversensing. [1]

My decision is to recommend the ICD, but I present it as a shared decision. The combination of a family history of SCD in a first-degree relative, confirmed NSVT, and extensive LGE tips me toward implantation despite the intermediate score. I would use the ESC HCM Risk-SCD calculator as the starting point and layer the major risk factors on top. I would explain to Mr Cooper that his brother's death, his NSVT, and his scar burden together place him in a group where the ICD offers a meaningful reduction in sudden death risk, and that the trade-off is the device morbidity over his lifetime. The Maron 2000 registry in the New England Journal of Medicine established that ICDs effectively terminate life-threatening arrhythmias in high-risk HCM, with an appropriate shock rate of about 5 per cent per year in the primary prevention cohort. I would document the discussion thoroughly and offer to involve his father, who has lived with an ICD, in the decision." [1]

Exercise and competitive sport: [1]

"This is the second pillar of his management and it is non-negotiable from a guideline standpoint, though it is emotionally difficult. The consensus recommendation, reflected in both the AHA and ACC and the ESC recommendations, is that patients with a confirmed diagnosis of HCM should NOT participate in competitive sport, regardless of symptom status, obstruction, or risk score. This is a Class I recommendation. Mr Cooper must retire from competitive cricket. [1]

The rationale is that intense exertion both triggers arrhythmia — through catecholamine surge, electrolyte flux, and mechanical stress — and accelerates the disease substrate. HCM is the single most common cause of sudden cardiac death in young athletes, and the data show that athletes with HCM who continue to compete have a substantially higher event rate than those who stop. The restriction applies to competitive and high-intensity sport; recreational, low-intensity aerobic activity — such as jogging, golf, or swimming laps — is permitted and encouraged for cardiovascular health. [1]

I would deliver this message with empathy and honesty, acknowledge that it is devastating for a semi-professional athlete, and connect him with a sports cardiologist and a psychologist experienced in athlete disqualification. I would also clarify that the restriction is indefinite, not temporary, because the arrhythmic substrate is permanent. I would document the discussion and the recommendation in writing, because this is a medico-legal as well as a clinical decision." [1]

Medical therapy and surveillance plan: [1]

"He is currently asymptomatic, so the role of medical therapy is not symptom relief — it is to address the dynamic obstruction and the diastolic dysfunction prophylactically. I would start a beta-blocker — bisoprolol 2.5 mg daily — which reduces heart rate and contractility, lengthens diastole to improve filling, and reduces the LVOT gradient. The target resting heart rate is around 60. I would avoid verapamil initially because of his athletic bradycardia and the risk of conduction disease. [1]

I would NOT start mavacamten — the cardiac myosin inhibitor proven in the EXPLORER-HCM trial in the Lancet 2020 — because he is asymptomatic; mavacamten is reserved for symptomatic obstructive HCM despite maximally tolerated medical therapy. It is held in reserve should he develop exertional symptoms. [1]

His surveillance plan: annual echocardiography to monitor wall thickness and LVOT gradient; annual 48-hour Holter for NSVT; cardiac MRI every two to three years to track scar progression; and an exercise test every two years. If he develops symptoms — dyspnoea, chest pain, presyncope — I would escalate to disopyramide, septal reduction therapy, or mavacamten depending on the phenotype." [1]

Examiner discussion questions

Q: "His brother's autopsy showed HCM. Should you be reviewing that autopsy report?" [1]

"Yes, absolutely. The autopsy report is a critical piece of evidence for two reasons. First, it confirms the cause of his brother's death as HCM-related and not another cause — such as a coronary anomaly, a channelopathy, or a toxin — that would change the family's risk profile. Second, the pathological details — the maximal wall thickness, the presence and extent of myocyte disarray and fibrosis, and any genetic testing performed on the brother — inform my own risk stratification. If the brother had a particularly thick septum or extensive fibrosis, that reinforces the aggressive nature of the familial mutation. [1]

I would also request, through the inherited cardiac conditions service, that any genetic testing performed on the brother post-mortem be reviewed. If a pathogenic sarcomeric variant — most commonly MYH7 or MYBPC3 — was identified in the brother, then targeted testing for that specific variant in Mr Cooper becomes the fastest route to confirming the genetic substrate, and it would streamline the cascade screening of the rest of the family. A molecular autopsy, if it was performed, is one of the most valuable pieces of information in a family with sudden death." [1]

Q: "His father has an ICD. Does knowing whether his father has received appropriate shocks change your decision?" [1]

"Yes, it does, and I would explicitly seek that information. If his father has received appropriate ICD therapy — a shock for ventricular tachycardia or fibrillation — that demonstrates that the familial mutation produces a phenotype susceptible to malignant ventricular arrhythmia, which strengthens the case for an ICD in the son. It provides direct, family-specific evidence of arrhythmia penetrance rather than relying on population averages. [1]

Conversely, if the father has had the ICD for over a decade without ever receiving an appropriate shock — only inappropriate shocks or none at all — that slightly tempers, but does not eliminate, the concern, because the father clearly had NSVT that prompted the implant, and genotype-phenotype correlation within a family is imperfect — the same sarcomeric mutation can produce different severity in different relatives due to modifier genes and environmental factors. I would incorporate the father's device interrogation data into the shared decision-making discussion, alongside the risk score and Mr Cooper's own NSVT and scar burden." [1]

Q: "What if he refuses the ICD and the exercise restriction?" [1]

"This is a situation where I must balance patient autonomy with my duty of care and my duty to protect a potentially vulnerable person. On the exercise restriction, I would be firm: I would explain the evidence clearly, document the recommendation and the discussion in writing, and make clear that my professional advice is to stop competitive sport. I cannot physically prevent him, but I would be explicit that continuing to compete against medical advice carries a substantial and avoidable risk of sudden death, and that this is documented. I would involve his club and, if relevant, the sporting body's medical officer, because organised sport has governance structures around athlete safety. [1]

On the ICD, this is a more nuanced shared decision because the risk score is intermediate, not high. I would respect a fully informed refusal, but only after I am satisfied he has capacity, understands the risks and benefits, and is making a voluntary choice. I would explore his reasons — fear of the device, impact on body image, athletic identity — and address them. I would offer to involve his father and partner in the discussion, and to give him time. I would document the capacity assessment and the discussion. If he remained firm, I would arrange close non-invasive surveillance — annual Holter, annual MRI — and maintain the conversation, because his risk may escalate over time as his phenotype evolves, and a future event or new finding may change his decision. I would NOT discharge him from care." [1]

Q: "How do you screen his younger sister?" [1]

"His sister is a first-degree relative of an affected proband with a probable familial mutation, so she falls under the cascade screening pathway. The strategy depends on whether a pathogenic variant has been identified in the family. If genetic testing in Mr Cooper or his deceased brother identifies a pathogenic sarcomeric variant, then the sister should have targeted genetic testing for that specific variant. If she is genotype-negative, she can be reassured and discharged from cardiac surveillance. If she is genotype-positive, she needs lifelong clinical surveillance with echocardiography, ECG, and Holter, beginning in childhood or adolescence, because HCM has age-dependent penetrance — she may be clinically silent now but develop hypertrophy and arrhythmia in her twenties or thirties. [1]

If no pathogenic variant is identified — which happens in 30 to 50 per cent of clinically definite HCM — then the sister undergoes serial clinical screening, because the family clearly has a familial cardiomyopathy. The standard schedule is echocardiography and ECG every one to three years from age 10 to 12 through to adulthood, with the interval lengthening if she remains normal. Any new symptoms — exertional chest pain, syncope, palpitations — prompt urgent reassessment. She should also be advised against competitive endurance sport until her status is clarified. The mother, who married into the family and is not a blood relative, does not require screening, but I would confirm the pedigree to exclude an unrecognised maternal cardiac history." [1]

DCE Short Case — Arrhythmogenic Right Ventricular Cardiomyopathy

Instruction

"This 22-year-old woman was referred after three episodes of palpitations and dizziness during competitive netball training. Examine her cardiovascular system and discuss your findings. You have 7 minutes for examination and 8 minutes for discussion." [1]

Key signs the patient demonstrates

• Palpitations and presyncope on exertion — the presenting complaint, reflecting ventricular ectopy from the dysplastic right ventricle
• Unremarkable resting cardiovascular examination — the examiner's trap: ARVC often has a normal physical examination at rest, and the diagnosis rests on the ECG, imaging, and family history
• A possible prominent V wave in the JVP if tricuspid regurgitation from RV dilatation is present (late finding)
• An S4 may be audible if RV compliance is reduced [1]

Presentation template (model)

"I examined Ms Nguyen's cardiovascular system. She is comfortable at rest at 45 degrees. There is no clubbing, pallor, or cyanosis. [1]

The pulse is regular at 74 beats per minute, normal volume. The blood pressure is 118 over 74. The JVP is not elevated. The apex beat is normally situated in the 5th intercostal space at the mid-clavicular line and is of normal character. [1]

On auscultation, the heart sounds are normal with no murmurs and no added sounds. The lungs are clear. [1]

The resting cardiovascular examination is essentially normal. However, given her history of exertional palpitations and presyncope in a competitive athlete, I am concerned about an inherited arrhythmogenic cardiomyopathy — particularly arrhythmogenic right ventricular cardiomyopathy, which is the leading cause of sudden cardiac death in young athletes after HCM and frequently has a normal resting examination. I would request a 12-lead ECG looking for T-wave inversion in V1 to V3 and epsilon waves, an echocardiogram and cardiac MRI to assess the right ventricle, a Holter monitor for ventricular ectopy of left bundle branch block morphology, and I would take a careful family history of sudden death." [1]

Discussion template

1. Summarise findings and the diagnostic concern [1]

"This young competitive athlete presents with exertional palpitations and presyncope, and her resting examination is normal — which is itself consistent with ARVC, where the structural disease is in the right ventricle and often clinically silent until an arrhythmic event. ARVC is an inherited heart muscle disease characterised by progressive fibrofatty replacement of the myocardium, predominantly affecting the right ventricle, predisposing to ventricular arrhythmia and sudden cardiac death. It is the second most common cause of sudden death in young athletes." [1]

2. Establish the genetic and pathophysiological basis [1]

"The inheritance is autosomal dominant with variable penetrance. The mutations are in genes encoding desmosomal proteins — the cell-cell adhesion complexes that bind cardiac myocytes. Plakophilin-2, or PKP2, is the most commonly mutated gene, found in 25 to 40 per cent of genotype-positive cases. Other genes include desmoglein-2, desmocollin-2, desmoplakin, and plakoglobin. Recessive forms cause the syndromic cardiocutaneous diseases — Naxos disease, with woolly hair, palmoplantar keratoderma, and ARVC. [1]

The pathophysiology is the desmosomal defect weakening myocyte-cell adhesion. Mechanical stress — especially intense exercise — causes myocyte detachment, necrosis, and apoptosis, and the healing response replaces dead myocardium with fibrous and fatty tissue. This produces the characteristic triangle of dysplasia — the inflow tract, outflow tract, and apex of the right ventricle are most affected. The fibrotic substrate supports re-entrant ventricular arrhythmias. The exercise hypothesis explains why ARVC presents in athletes, why it is more severe and earlier in competitive athletes, and why sport restriction is a core management decision." [1]

3. Apply the 2010 Revised Task Force Criteria [1]

"The diagnosis integrates structural, histological, ECG, arrhythmic, and familial findings, each categorised as major or minor, using the 2010 Revised Task Force Criteria published by Marcus and colleagues in Circulation in 2010. Definite ARVC requires two major, or one major and two minor, or four minor criteria from different categories. [1]

On her ECG, I am looking for T-wave inversion in V1 to V3 or beyond, in the absence of complete right bundle branch block, in a patient over 14 — a major repolarisation criterion. I am also looking for epsilon waves — distinct low-amplitude deflections at the end of the QRS complex in V1 to V3, which are pathognomonic but insensitive, present in only about 30 per cent. A terminal activation delay of the QRS in V1 to V3 of 55 milliseconds or more is a minor depolarisation criterion. [1]

On imaging, echocardiography and cardiac MRI look for regional right ventricular akinesia, dyskinesia, or aneurysm, with RV dilatation or dysfunction — these are the structural criteria. The cardiac MRI also assesses for right ventricular fatty replacement and wall thinning, though fat alone is non-specific and the functional and dimensional criteria are the formal Task Force parameters. [1]

On Holter, I am looking for ventricular ectopy of left bundle branch block morphology — indicating a right ventricular origin — and specifically non-sustained or sustained VT of LBBB morphology with a superior axis, which is a major arrhythmia criterion highly specific for RV dysplasia." [1]

4. The exercise restriction — the core decision [1]

"This is the management decision the examiners will press. The evidence is clear and consistent: continued intense exercise accelerates disease progression, increases arrhythmia burden, and increases the risk of sudden cardiac death in ARVC. Studies of ARVC patients show that those who continue competitive sport have a more than five-fold higher rate of arrhythmic events and faster disease progression than those who stop. The desmosomal damage is mechanically driven, and each episode of intense exertion worsens the myocyte detachment and fibrofatty replacement. [1]

The recommendation, reflected in both the ESC and the AHA and ACC consensus documents, is absolute and unconditional: Ms Nguyen must stop all competitive sport and restrict to low-intensity recreational activity only. This is regardless of whether she is symptomatic, regardless of her Task Force score, and regardless of whether she receives an ICD. The ICD protects her from a fatal arrhythmia but does NOT make it safe to return to competitive sport — the sport itself accelerates the disease. I would deliver this message clearly and compassionately, acknowledge the impact on an athlete, and involve a sports cardiologist and psychologist." [1]

5. ICD and medical therapy [1]

"Whether she needs an ICD depends on her Task Force criteria and her arrhythmia burden. If her Holter or her presentation documents sustained VT, or if she has syncope presumed arrhythmic, or if she has a family history of sudden death in a first-degree relative with confirmed ARVC, she meets the criteria for a primary prevention ICD. Beta-blocker is first-line for symptom and arrhythmia control, and I would start nadolol or metoprolol. Amiodarone or catheter ablation is reserved for recurrent ventricular arrhythmia despite beta-blockade, recognising that ablation in ARVC has a high recurrence rate because the substrate is diffuse and progressive — ablation treats a focus, not the disease, and new foci emerge over time." [1]

Examiner: "Her ECG shows T-wave inversion in V1 to V3. Is that not just normal in a young woman?" [1]

"T-wave inversion in V1 to V3 can be a normal juvenile pattern, but it persists beyond adolescence only in a minority and it is a recognised marker of ARVC. The key discriminator is the age and the context. The juvenile T-wave pattern — inverted in V1 to V3 — is considered normal in children and in some young adults, particularly athletes and young Black women, up to about age 16 to 18 in leads V1 to V2. Beyond V2, or persisting after puberty in leads V1 to V3, it should be regarded with suspicion. [1]

In Ms Nguyen, who is 22 and symptomatic with exertional presyncope, T-wave inversion in V1 to V3 is not a benign juvenile pattern — it is a major Task Force repolarisation criterion for ARVC until proven otherwise. The other consideration is the differential: T-wave inversion in V1 to V3 without right bundle branch block also raises pulmonary embolism, right ventricular hypertrophy, and the Brugada pattern, but in the clinical context of a young athlete with exertional arrhythmia, ARVC is the leading diagnosis. I would proceed to echocardiography and cardiac MRI to seek the structural criteria and confirm or exclude the diagnosis. If imaging is normal and she has only the repolarisation criterion, she would meet only a single major criterion and would not yet reach a definite diagnosis — she would be classified as borderline and undergo continued surveillance with serial ECG and Holter and repeat imaging." [1]

Examiner: "What do you tell her about her future children?" [1]

"ARVC is autosomal dominant, so each of her children has a 50 per cent chance of inheriting the mutation. I would explain this clearly and offer genetic counselling, ideally before she embarks on a pregnancy. If a pathogenic desmosomal variant is identified in her, then her children can be tested for that specific variant after birth, and cascade screening applies to all first-degree relatives on her side. I would reassure her that having the gene does not guarantee disease — penetrance is variable and incomplete — but it does mean surveillance. The discussion is sensitive and I would frame it constructively: ARVC is a manageable condition with modern therapy, the goal of testing is to prevent sudden death through early diagnosis, and reproductive options including pre-implantation genetic diagnosis are available if she wishes." [1]