Hypertrophic cardiomyopathy — structured written assessment

SAQ 1 (10 marks)

This scenario is fictional and invented for teaching. A 24-year-old man is referred after a murmur at a pre-season sports medical. He reports exertional breathlessness and one unexplained episode of syncope four months ago. His uncle died suddenly aged 35 with HCM at autopsy. Echocardiography shows asymmetric septal hypertrophy of 22 mm, LV cavity not dilated, LVEF 70% and a resting LVOT gradient of 20 mm Hg. He is normotensive, and further assessment finds no other cardiac, systemic or metabolic cause of the hypertrophy.

1. State the diagnosis and the criterion he meets under the 2023 ESC and 2024 AHA/ACC guidelines. (2) ^{[2] [1]}
2. His resting gradient is small. Describe how you would assess for obstruction. (3) ^{[2] [1]}
3. Outline his sudden-death risk assessment under each guideline. (5) ^{[2] [1] [4] [20]}

Model answers

1. Hypertrophic cardiomyopathy. ESC 2023: LV wall thickness of 15 mm or more in any segment not explained solely by loading conditions. AHA/ACC 2024: maximal end-diastolic wall thickness of 15 mm or more anywhere in the LV without another cause. He was seen at a sports medical, and AHA/ACC lists athletic remodelling as a cause to exclude; if athletic remodelling and other causes are excluded, his 22 mm septum meets both.^[2][1]
2. Resting echo tends to underestimate ambulatory obstruction; AHA/ACC notes that LVOT gradients can be missed on resting echocardiography in up to 50% of patients with obstructive physiology.^[1] ESC recommends Valsalva in the sitting and semi-supine position, then standing if no gradient appears, in all patients at initial evaluation (Class I); AHA/ACC recommends TTE with provocative manoeuvres when the resting peak gradient is below 50 mm Hg (COR 1). If bedside manoeuvres fail to induce 50 mm Hg or more in a symptomatic patient, perform exercise stress echo. Dobutamine is not advised.^[2] Obstruction is a peak gradient of 30 mm Hg or more. A gradient of 50 mm Hg or more is the threshold for contemplating advanced therapy when symptoms are refractory to standard management (AHA/ACC) and is usually considered the threshold for invasive treatment (ESC).^[2][1]
3. ESC 2023: calculate the HCM Risk-SCD estimate first (he is 16 or older; ESC says the models should not be used in elite athletes, so first confirm he is not one). Inputs are age, maximal wall thickness, left atrial diameter, LVOT gradient, family history of SCD, NSVT and unexplained syncope; the models do not use exercise-induced LVOT gradients.^[2][4] ESC counts non-neurocardiogenic syncope that remains unexplained after investigation (episodes within 6 months may be more predictive). Definitions of family history vary; ESC usually considers it significant when a first-degree relative died suddenly under 40, or at any age with established HCM, so his uncle (a second-degree relative) would not usually count.^[2] ESC 2023 then says an ICD should be considered at an estimated 5-year risk of 6% or more (Class IIa), after detailed clinical assessment of lifelong complication risk, competing mortality from the disease and comorbidities, and the impact on lifestyle, socio-economic status and psychological health. It may be considered in individual patients at 4% to below 6% (Class IIb), after detailed assessment of lifelong complication risk and the impact on lifestyle, socio-economic status and psychological health.^[2] The same cut-offs defined the 2014 ESC categories.^[20] In the external-validation complete-case analysis (n=2147), a predicted risk of 6% or more carried an observed 5-year SCD incidence of 8.9%.^[19] AHA/ACC 2024: look for major risk factors. Recent syncope qualifies if suspected by history to be arrhythmic, ie unlikely to be vasovagal and not attributable to LVOTO; AHA/ACC weights episodes within 6 months especially, and events more than 5 years ago do not appear relevant. Sudden death judged definitively or likely due to HCM in a first-degree or close relative aged 50 or under counts, and close relatives would generally be second-degree relatives, so his uncle (aged 35, HCM at autopsy) counts if his death is judged definitively or likely attributable to HCM. In adults with one or more major risk factors, it is reasonable to offer an ICD (COR 2a), and discussing the estimated 5-year sudden death risk and mortality rates can be useful in shared decision-making about an ICD (COR 2a).^[1][28] Complete both with 24–48 h ambulatory monitoring for NSVT (AHA/ACC) and CMR, which ESC recommends at baseline in patients with HCM; AHA/ACC adds that if, after clinical assessment including history, echo and ambulatory monitoring, he is not otherwise identified as high risk, or risk stratification remains uncertain, CMR characterises wall thickness, EF, apical aneurysm and LGE.^[1][2]

SAQ 2 (10 marks)

This scenario is fictional and invented for teaching. A 55-year-old woman with obstructive HCM remains NYHA class III on the maximum tolerated dose of a non-vasodilating beta-blocker. Her resting heart rate has fallen to 56 bpm on treatment. Provoked LVOT gradient is 90 mm Hg and LVEF 68%. She has new paroxysmal AF with a CHA2DS2-VASc score of 1.

1. Outline the escalation options for her obstruction under each guideline, with trial evidence. (5) ^{[1] [2] [5] [6]}
2. When would septal reduction be considered and how do the two procedures compare? (3) ^{[2] [11] [12]}
3. How do you manage the AF? (2) ^{[2] [1]}

Model answers

1. Her resting heart rate, suppressed to 56 bpm on treatment, is the physiological evidence of beta-blockade that AHA/ACC requires before beta-blocker failure is declared.^[1] For persistent symptoms from LVOTO despite a beta-blocker, AHA/ACC 2024 gives COR 1 to adding a myosin inhibitor (adults), disopyramide (with an AV nodal blocker) or SRT at an experienced centre.^[28] Without a direct head-to-head comparison, the ESC 2023 Task Force could not recommend myosin inhibitors as first-line therapy, but said second-line use should be considered when optimal medical therapy with beta-blockers, calcium antagonists and/or disopyramide is ineffective or poorly tolerated. Its Class IIa row: in adults with resting or provoked LVOTO, mavacamten titrated to the maximum tolerated dose with echocardiographic LVEF surveillance should be considered in addition to a beta-blocker (or, if that is not possible, with verapamil or diltiazem) to improve symptoms. ESC advises not combining it with disopyramide in the absence of evidence to the contrary, and monitoring up-titration to a maximum of 15 mg with echocardiography in accordance with licensed recommendations. Disopyramide, titrated to maximum tolerated dose and added to a beta-blocker (or to verapamil or diltiazem if a beta-blocker is not possible) to improve symptoms in resting or provoked LVOTO, is ESC Class I. The maximum tolerated dose is usually 400–600 mg/day, with dose reduction if QTc exceeds 500 ms, and ESC advises avoiding it with other QT-prolonging drugs such as amiodarone or sotalol, which matters if amiodarone is chosen for her AF.^[2] In EXPLORER-HCM (mavacamten starting at 5 mg), 37% on mavacamten versus 17% on placebo met the primary endpoint over the 30-week treatment period: a pVO2 increase of 1.5 ml/kg/min or more with at least one NYHA class reduction, or a 3.0 ml/kg/min or greater increase without NYHA worsening.^[5] VALOR-HCM: 17.9% on mavacamten versus 76.8% on placebo met guideline criteria for SRT or underwent it at 16 weeks.^[6] Stop a myosin inhibitor if LVEF falls persistently below 50% (AHA/ACC COR 1).^[28]
2. ESC recommends SRT for a resting or maximum provoked gradient of 50 mm Hg or more in NYHA/Ross class III–IV despite maximum tolerated medical therapy (Class I), and says it should be considered for recurrent exertional syncope caused by a resting or maximum provoked gradient of 50 mm Hg or more despite optimal medical therapy (Class IIa).^[2] Myectomy abolishes or substantially reduces the gradient in over 90% (ESC). In a series of 289 myectomy patients, procedural mortality was 0.8% and 10-year survival matched the general population.^[2][11] Alcohol septal ablation needs myocardial contrast echo beforehand, its main non-fatal complication is AV block in 7–20%, and repeat procedures after it (7–20%) are more frequent than after myectomy. In the Euro-ASA registry (1275 highly symptomatic patients treated with alcohol septal ablation), 30-day mortality was 1%.^[2][12]
3. Anticoagulate whatever the CHA2DS2-VASc score: ESC 2023 recommends oral anticoagulation, unless contraindicated, in all patients with HCM and AF or atrial flutter (Class I), and AHA/ACC makes a DOAC (or alternatively warfarin) the default.^[2][1] On drug choice, ESC notes there are no randomised data comparing DOACs with VKAs in cardiomyopathy, although data suggest they may be used as in the general population, where DOACs are preferred in patients without severe mitral stenosis and/or a mechanical valve prosthesis.^[2] Given the poor tolerance of AF in HCM, rhythm control is often preferred, and amiodarone is generally deemed a favoured option (AHA/ACC). ESC advises prompt restoration of sinus rhythm or rate control because new-onset or poorly controlled AF can exacerbate LVOTO symptoms.^[1][2]