Cardiomyopathies Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr Daniel Reeves is a 31-year-old primary school teacher referred to the heart failure clinic after an echo performed for exertional dyspnoea and two episodes of pre-syncope showed a dilated left ventricle with an ejection fraction of 28 per cent, global hypokinesis, and moderate functional mitral regurgitation. He has no past medical history of note and takes no regular medications. He does not smoke, drinks alcohol occasionally, and has never used recreational drugs. [1]

There is a striking family history: his father died suddenly at 42 with a diagnosis of dilated cardiomyopathy and had a permanent pacemaker for complete heart block; his paternal aunt has a cardiac defibrillator. There is no consanguinity. [1]

On examination he is comfortable at rest. The pulse is regular at 72 beats per minute, blood pressure 118 over 74. The apex beat is displaced to the 6th intercostal space, anterior axillary line, and is diffuse in character. There is a third heart sound and a soft pansystolic murmur at the apex radiating to the axilla. The JVP is not elevated, the lungs are clear, and there is no peripheral oedema. [1]

His ECG shows sinus rhythm with first-degree AV block and a left bundle branch block, QRS 138 milliseconds. His coronary angiogram is normal, excluding ischaemic cardiomyopathy. His cardiac MRI confirms a dilated LV with severe systolic dysfunction, mid-wall late gadolinium enhancement in the interventricular septum, and no evidence of myocarditis or infiltration. His Holter monitor recorded frequent premature ventricular complexes and a three-beat run of non-sustained ventricular tachycardia. Genetic testing is pending. [1]

His problems are:

1. Non-ischaemic dilated cardiomyopathy with HFrEF — the primary problem
2. A probable familial genetic substrate — the family history of DCM with conduction disease in his father, combined with his own first-degree AV block and LBBB at age 31, raises an LMNA mutation as the leading genetic candidate
3. Arrhythmia risk — NSVT and a wide QRS in the context of probable LMNA, which confers an arrhythmia risk disproportionate to the ejection fraction
4. The ICD decision — the central management question, and one I must justify against the DANISH trial
5. Family screening and genetic counselling — cascade evaluation of first-degree relatives [1]

My working diagnosis is familial dilated cardiomyopathy, with a probable LMNA truncating variant given the early conduction disease and family history of sudden death. My priorities are to optimise guideline-directed medical therapy, make a reasoned ICD decision, and initiate cascade family screening through an inherited cardiac conditions service." [1]

Examiner probing questions and model answers

Q1: "You mentioned LMNA. Why does this particular gene change the way you think about his arrhythmia risk?" [1]

"LMNA encodes lamin A and C, nuclear envelope proteins. Mutations — typically truncating variants — produce a distinctive phenotype of progressive conduction disease and arrhythmia that precedes and out of proportion to the development of systolic dysfunction. The mechanism is thought to be mechanical stress-induced myocyte necrosis from the defective nuclear envelope, with fibrofatty replacement of the conduction system. [1]

The clinical implication is critical and is a recognised exam trap: in LMNA cardiomyopathy, sudden cardiac death can occur at a relatively preserved ejection fraction — the standard guideline thresholds for primary prevention ICD, which are based on an EF of 35 per cent or less, under-estimate the risk in this genotype. Several cohort studies show appropriate ICD therapy rates of 10 to 15 per cent per year in LMNA carriers, far exceeding the risk implied by the EF alone. For this reason, the presence of an LMNA mutation with any degree of ventricular dysfunction, conduction disease, or NSVT is a strong argument for a primary prevention ICD regardless of whether the EF sits above or below 35 per cent. This man has the full triad — conduction disease, systolic dysfunction, and NSVT — so even before his genotype returns, my index of suspicion is high." [1]

Q2: "He has an EF of 28 per cent and non-ischaemic DCM. Walk me through your ICD decision and how the DANISH trial informs it." [1]

"This is the pivotal question and I will reason through it explicitly. The traditional guideline indication for a primary prevention ICD in non-ischaemic systolic heart failure is an LVEF of 35 per cent or less after at least three months of optimal guideline-directed medical therapy, in NYHA class II to III, with a reasonable survival expectation beyond one year. By that rule, he qualifies on the EF criterion. [1]

However, the DANISH trial, published by Kober and colleagues in the New England Journal of Medicine in 2016, randomised 1116 patients with non-ischaemic systolic heart failure to prophylactic ICD implantation or usual clinical care. After a median follow-up of 67.6 months, prophylactic ICD implantation did NOT significantly reduce all-cause mortality — 21.6 per cent in the ICD group versus 23.4 per cent in the control group, hazard ratio 0.87, 95 per cent confidence interval 0.68 to 1.12, P equals 0.28. The ICD did halve the rate of sudden cardiac death, from 8.2 per cent to 4.3 per cent, hazard ratio 0.50, but this did not translate into an overall survival benefit, likely because of competing causes of death in an older, comorbid non-ischaemic population. [1]

The DANISH trial has changed practice by making the ICD decision in non-ischaemic DCM more individualised rather than automatic. Two features of THIS patient pull me back toward recommending an ICD despite DANISH. First, he is young — 31 — and the subgroup analyses of DANISH consistently show that the survival benefit of ICD is concentrated in younger patients, with those under 70 — and especially under 60 — deriving more benefit, because they have fewer competing causes of death. Second, and more importantly, he has a probable LMNA mutation, which DANISH did not specifically study — DANISH enrolled by EF, not by genotype. An LMNA carrier with NSVT and conduction disease carries an arrhythmia risk that the trial's average effect does not capture. [1]

So my decision is: I will implant a primary prevention ICD, but not until he has completed at least three months of optimised guideline-directed medical therapy, during which I will reassess the ejection fraction. If the EF recovers to above 35 per cent — which can happen with excellent GDMT — I would STILL recommend the ICD because of the probable LMNA genotype and his NSVT, and I would explain to the patient that the genotype, not the EF, is driving that decision. I would involve the inherited cardiac conditions team and, if LMNA is confirmed, use the validated LMNA risk prediction model to support the discussion." [1]

Q3: "Detail his guideline-directed medical therapy." [1]

"He has HFrEF with an EF of 28 per cent, NYHA class II. I will initiate all four pillars of guideline-directed medical therapy, working them up over weeks rather than waiting for full up-titration of each. [1]

Pillar one — the renin-angiotensin system modifier. I will start sacubitril-valsartan, target dose 97 over 103 mg twice daily. The PARADIGM-HF trial, McMurray and colleagues in the New England Journal of Medicine 2014, established ARNI superiority over enalapril: the primary composite of cardiovascular death or heart failure hospitalisation was reduced by 20 per cent, hazard ratio 0.80, and all-cause mortality was reduced, hazard ratio 0.84. If ARNI is not tolerated or available, an ACE inhibitor such as ramipril or an ARB such as candesartan is the alternative. I will start low — sacubitril-valsartan 24 over 26 mg twice daily — and up-titrate every two to four weeks, monitoring blood pressure and renal function. [1]

Pillar two — a beta-blocker. I will use bisoprolol, carvedilol, or metoprolol succinate, the three proven to reduce mortality. Start at a low dose — bisoprolol 1.25 mg daily — and double every two weeks to the target of 10 mg daily, tolerating a systolic pressure down to 100. [1]

Pillar three — a mineralocorticoid receptor antagonist. Spironolactone 12.5 to 25 mg daily, or eplerenone 25 to 50 mg daily if gynaecomastia is a concern. I will monitor potassium and renal function at one week, one month, and every three months. [1]

Pillar four — an SGLT2 inhibitor. Dapagliflozin 10 mg daily or empagliflozin 10 mg daily. The DAPA-HF trial, McMurray and colleagues in the New England Journal of Medicine 2019, showed that dapagliflozin reduced the primary composite of worsening heart failure or cardiovascular death by 26 per cent, hazard ratio 0.74, and this benefit is independent of diabetes status. The SGLT2 inhibitors are the one pillar I can start at full dose immediately — they do not require up-titration — so I will begin this at the first visit. [1]

I will add a loop diuretic, furosemide 20 to 40 mg daily, only if he is congested — he is currently euvolaemic, so I will hold off. I will recheck the echocardiogram at three months to reassess the EF, which informs both the ICD timing and the ongoing GDMT intensity. I will also ensure his iron studies are checked — iron deficiency with or without anaemia is common in HFrEF and, if present, intravenous ferric carboxymaltose improves symptoms and exercise capacity." [1]

Q4: "He has a left bundle branch block with a QRS of 138 milliseconds. Does he need cardiac resynchronisation therapy?" [1]

"Not at present. The standard indication for CRT is an LVEF of 35 per cent or less with a left bundle branch block and a QRS duration of 150 milliseconds or more, in NYHA class II to IV, despite at least three months of optimal GDMT. His QRS is 138 milliseconds, which sits below the 150 threshold where the CRT benefit is most consistent. The evidence consistently shows that the narrower the QRS, the smaller — and potentially absent — the CRT benefit, and that a non-LBBB or a QRS under 130 to 140 milliseconds may even be harmed by unnecessary right ventricular pacing. [1]

So at 138 milliseconds I would NOT implant a CRT device now. However, this is relevant to my device decision in another way: if I am implanting an ICD and there is any chance he will need significant ventricular pacing — for example, if his conduction disease progresses, which is expected with LMNA — then I would choose a device capable of delivering CRT or at minimum minimise right ventricular pacing through programming, because chronic right ventricular apical pacing induces a dyssynchrony that can worsen systolic function. If he later develops a QRS over 150 milliseconds, CRT upgrade would be reconsidered. The progression of his conduction disease is something I will monitor at every visit." [1]

Q5: "When would you refer him for transplant assessment?" [1]

"I would refer early rather than late, because transplant evaluation takes months and the window for listing can narrow quickly. The specific triggers for transplant referral in this man are: first, persistent severe LV dysfunction — EF 30 per cent or less — despite at least three to six months of optimal, tolerated GDMT and device therapy; second, two or more heart failure hospitalisations in the preceding 12 months; third, a rising NT-proBNP or declining peak VO2 on cardiopulmonary exercise testing, which is the objective measure of functional limitation and one of the strongest predictors of outcome; and fourth, recurrent appropriate ICD therapy or sustained ventricular arrhythmia refractory to medical therapy, which signals an arrhythmic phenotype that may mandate urgent evaluation and listing. [1]

In his case, with a probable LMNA mutation, I would refer earlier than the generic EF threshold suggests, because LMNA carriers can deteriorate rapidly and the conduction disease may suddenly progress. I would request a baseline cardiopulmonary exercise test now, and serial NT-proBNP, and refer to the transplant service if his peak VO2 falls below 14 mL per kg per minute or below 50 per cent predicted, or if he fails to recover EF with optimised therapy. The transplant assessment also allows me to quantify pulmonary vascular resistance — a fixed, elevated trans-pulmonary gradient would contraindicate transplant — and to begin the psychosocial and adherence evaluation that listing requires." [1]

Q6: "His father had DCM and died suddenly. How do you manage his family?" [1]

"A three-generation pedigree is mandatory, and this is where the inherited cardiac conditions service is central. I would draw the pedigree: his father with DCM, sudden death at 42, and a pacemaker for complete heart block; his paternal aunt with an ICD; and then extend it to his siblings, any children, and his paternal grandparents. [1]

The cascade screening strategy depends on the genetic result. If LMNA or another pathogenic variant is identified in the proband — him — then first-degree relatives undergo targeted genetic testing for that specific variant. Those who are genotype-positive have the variant and need clinical surveillance with echocardiography, ECG, and Holter, starting in childhood for LMNA given the early conduction disease, and continuing lifelong. Those who are genotype-negative are reassured and discharged from the cardiac clinic — this is the power of cascade genetic testing, it distinguishes affected from unaffected relatives without years of serial screening. [1]

If the genetic testing is negative — which it is in roughly half of familial DCM — then first-degree relatives undergo serial clinical screening with echocardiography and ECG, typically every one to three years from adolescence, because the family clearly has a familial cardiomyopathy even if the gene is unknown. His own children, if he has any, would be screened on the same schedule. I would also advise that all at-risk relatives avoid competitive endurance sport and that any new symptoms — palpitations, syncope, exertional dyspnoea — prompt urgent reassessment. The family is also offered genetic counselling, including the implications for reproductive planning, since the inheritance is autosomal dominant with a 50 per cent chance of transmission to each child." [1]

Q7: "What is your prognostic discussion with him?" [1]

"I would be honest and hopeful in measured terms. I would explain that he has a genetic heart muscle condition that is treatable but not curable, that modern therapy — the four-pillar medication regimen and a defibrillator — substantially reduces his risk of deterioration and sudden death, and that with optimal management many patients with this condition live for decades with a good quality of life. I would explain that the defibrillator is specifically to protect him from the arrhythmia risk that runs in his family, and that his father's outcome is exactly what the ICD is designed to prevent. [1]

I would also be honest that the condition can progress — the EF may not fully recover, he may need a transplant in the future, and the conduction disease may advance — and that this is why close follow-up matters. I would encourage him to ask questions, to bring his partner or family to appointments, and to engage with the cardiac rehabilitation and the inherited cardiac conditions service. I would discuss lifestyle: moderation of alcohol, avoidance of competitive sport and heavy isometric exertion, and the importance of medication adherence. I would NOT give him a specific survival number — the precision is false and it would be harmful — but I would anchor his expectations on the principle that optimal therapy, early device implantation, and family surveillance together give him the best achievable outcome." [1]

Short Case — Hypertrophic Cardiomyopathy with Dynamic Manoeuvres

Scenario

"Examine this 28-year-old man's cardiovascular system. He was referred after a murmur was heard at a routine medical." [1]

Candidate presentation (model)

"I examined Mr Carter's cardiovascular system. He is comfortable at rest at 45 degrees. There is no clubbing, pallor, or cyanosis. I note no stigmata of syndromic or phenocopy conditions — no angiokeratomas to suggest Fabry disease, no features of Noonan syndrome. [1]

The radial pulse is regular at 66 beats per minute, of normal volume but with a jerky, rapid-rising character. The carotid pulse is brisk in upstroke with a transient peak. The blood pressure is 128 over 76, with a normal pulse pressure. The JVP is not elevated. [1]

The apex beat is in the 4th intercostal space at the mid-clavicular line and is bifid in character, with a palpable atrial impulse followed by the ventricular impulse — a double apical impulse. There is a systolic thrill at the lower left sternal edge. [1]

On auscultation, the first heart sound is normal and the second heart sound is preserved with normal physiological splitting. There is a harsh ejection systolic murmur at the lower left sternal edge and apex, which does not radiate to the carotids. With the Valsalva manoeuvre, the murmur becomes louder; with passive squatting and with sustained handgrip, the murmur becomes softer. There is no diastolic murmur and no pericardial rub. [1]

In summary, these findings — the bifid apex beat, the ejection systolic murmur at the lower left sternal edge that increases on Valsalva and decreases on squatting — are consistent with hypertrophic cardiomyopathy with dynamic left ventricular outflow tract obstruction. I would confirm the diagnosis with echocardiography, perform a cardiac MRI with late gadolinium enhancement, and stratify the sudden cardiac death risk with the HCM Risk-SCD calculator, Holter monitoring, and an exercise test." [1]

Examiner Q and A on dynamic manoeuvres

Examiner: "Explain why the Valsalva manoeuvre makes this murmur louder." [1]

"The Valsalva manoeuvre, in its strain phase, produces a sustained forced expiration against a closed glottis. This has two relevant haemodynamic effects: it increases intrathoracic pressure, which reduces venous return and therefore reduces left ventricular preload; and it reduces afterload transiently through compression of the aorta. The net effect is a smaller left ventricular cavity with reduced filling. [1]

In hypertrophic cardiomyopathy, the dynamic outflow tract obstruction depends on the size of the LV cavity relative to the hypertrophied septum — a smaller cavity brings the anterior mitral leaflet closer to the septum and worsens the systolic anterior motion, increasing the gradient. So the reduced preload from Valsalva makes the LV smaller, increases the SAM, and the murmur gets louder. This is the opposite of a fixed valvular obstruction like aortic stenosis, where reduced preload means less stroke volume across a fixed orifice and a softer murmur. The Valsalva response is the single most reliable bedside discriminator between HCM and aortic stenosis — HCM gets louder, aortic stenosis gets softer." [1]

Examiner: "And why does squatting make it softer?" [1]

"Squatting does the opposite of standing or Valsalva. It increases venous return — compressing the leg veins increases preload, filling the LV more — and it increases afterload, through compression of the abdominal aorta and femoral arteries. A larger, better-filled LV keeps the outflow tract wider, reducing the proximity of the mitral leaflet to the septum and reducing the SAM and the gradient, so the murmur softens. The increased afterload also reduces the dynamic obstruction directly. Handgrip works through the same afterload mechanism — sustained isometric contraction raises systemic vascular resistance, increases afterload, reduces the LVOT gradient, and softens the murmur. [1]

I use these manoeuvres at the bedside in a specific sequence. I listen at the lower left sternal edge in the sitting position, then ask the patient to stand up suddenly — the HCM murmur gets louder while an aortic stenosis murmur softens; then ask them to squat — the HCM murmur softens while aortic stenosis gets louder; then handgrip — again HCM softens. The mitral valve prolapse click-murmur also changes with these manoeuvres, but in MVP the click moves closer to S1 and the murmur lengthens on standing and Valsalva, which distinguishes it from HCM where the murmur simply gets louder." [1]

Examiner: "How would you risk-stratify him for sudden cardiac death?" [1]

"Sudden cardiac death risk stratification is the single most important decision in HCM, because HCM is the leading cause of SCD in young athletes. I use two complementary frameworks. [1]

The first is the HCM Risk-SCD calculator, developed by O'Mahony and colleagues from the European Heart Journal 2014, a multivariable model from a cohort of 3675 patients. It integrates seven variables — age, maximal wall thickness, left atrial diameter, maximal LVOT gradient, family history of sudden death, non-sustained VT on Holter, and unexplained syncope — to estimate a five-year risk of SCD. The result guides the ICD recommendation: a risk of 4 per cent or less is low risk and an ICD is generally not indicated; 4 to under 6 per cent is intermediate and an ICD may be considered; and 6 per cent or more is high risk and an ICD should be considered. [1]

The second framework is the 2020 AHA and ACC guideline major-risk-factor approach, which lists the established markers that individually support ICD consideration: massive LVH with a maximal wall thickness of 30 mm or more; family history of SCD in a first-degree relative under 50; unexplained syncope; non-sustained VT; and an abnormal blood pressure response to exercise, defined as a failure to rise by at least 20 mmHg systolic or a drop during exercise. [1]

I would apply both. I need an echocardiogram to measure the maximal wall thickness and LVOT gradient; a 24 to 48 hour Holter to detect NSVT; an exercise test to measure the blood pressure response; and a cardiac MRI to assess the extent of late gadolinium enhancement, which is an emerging prognostic marker that the calculator does not formally include but which, when extensive, supports ICD consideration in borderline cases. I would then present the calculated risk to the patient in the context of the major risk factors and engage in shared decision-making, because the ICD carries real morbidity — inappropriate shocks, infection, lead failure — and the decision must balance the risk of SCD against these harms." [1]

Examiner: "When is an ICD not a calculator question?" [1]

"For secondary prevention. If this man had survived a cardiac arrest or had a documented episode of spontaneous sustained ventricular tachycardia, he would receive an ICD regardless of the HCM Risk-SCD score. The calculator is for primary prevention only — estimating risk in someone who has not yet had a life-threatening arrhythmic event. The Maron registry, published in the New England Journal of Medicine in 2000, established the efficacy of the ICD for terminating life-threatening arrhythmias in high-risk HCM, with an appropriate shock rate of about 5 per cent per year in the primary prevention cohort. Once a patient has had an event, that question is answered — they are high-risk and the ICD is indicated, full stop." [1]

Examiner: "What drugs are absolutely contraindicated in obstructive HCM and why?" [1]

"The drugs to avoid in obstructive HCM are those that reduce preload, reduce afterload, or increase contractility — because all three worsen the dynamic LVOT obstruction. [1]

Pure afterload reducers — hydralazine and other direct vasodilators — drop the systemic vascular resistance, the LV ejects more forcefully against a lower resistance, the cavity shrinks, and the SAM and gradient worsen. Nitrates, including sublingual glyceryl trinitrate, reduce preload by venodilation, shrink the LV, and worsen obstruction — this is a classic exam trap, because a patient with HCM may be given a nitrate for angina-like chest pain and deteriorate. Diuretics, if used aggressively, do the same through volume depletion. Positive inotropes — digoxin, and in the acute setting dopamine or dobutamine — increase contractility, which directly worsens the SAM and the gradient, and are contraindicated unless the patient is in end-stage burned-out HCM with systolic dysfunction and no residual obstruction. Low-dose diuretics are sometimes used cautiously for pulmonary congestion but only with great care. [1]

The safe drugs are the negative inotropes and chronotropes: beta-blockers, which are first-line; the non-dihydropyridine calcium channel blockers verapamil and diltiazem as an alternative or addition; and disopyramide, the class Ia antiarrhythmic with a powerful negative inotropic effect, for refractory obstruction. Mavacamten, the cardiac myosin inhibitor proven in the EXPLORER-HCM trial in the Lancet in 2020, is the newest option for symptomatic obstructive HCM despite maximal medical therapy." [1]