Hypertrophic cardiomyopathy — structured viva

Stem

This scenario is fictional and invented for teaching. You are the consultant in a cardiomyopathy clinic. A 19-year-old competitive swimmer was referred after an incidental murmur. Her echocardiogram reports a maximal LV wall thickness of 13 mm. Her father has HCM.

Branch A — Is this HCM?

Examiner: Thirteen millimetres. Does she have HCM?

Strong answer: In a general adult the threshold is 15 mm in any segment, not explained solely by loading conditions (ESC), or anywhere in the LV without another cause (AHA/ACC). She is an adult first-degree relative; if her father's HCM is unequivocal, ESC 2023 bases her diagnosis on a wall thickness of 13 mm or more. AHA/ACC agrees that 13–14 mm can be diagnostic in a family member.^[2][1]

Examiner: How would you separate this from athletic remodelling?

Strong answer: AHA/ACC lists athletic remodelling as a secondary cause of LVH to exclude.^[1] On CMR, absence of fibrosis may favour physiological adaptation, but LGE can be absent in young people and mild HCM. ^[2] In child gene carriers, ECG changes can precede LVH.^[1] Genetic testing helps: if her father carries a pathogenic or likely pathogenic variant, cascade testing with pre- and post-test counselling is recommended for adult at-risk relatives such as her (ESC Class I).^[2]

Branch B — Obstruction

Examiner: Her resting gradient is 12 mm Hg. Is she nonobstructive?

Strong answer: Not yet proven. LVOTO is dynamic and sensitive to preload, afterload and contractility.^[1] ESC asks for Valsalva sitting and semi-supine, then standing if no gradient appears, in all patients at initial evaluation (Class I); with a resting gradient below 50 mm Hg, AHA/ACC recommends TTE with provocative manoeuvres (COR 1). In symptomatic patients, exercise echo follows if bedside manoeuvres do not induce 50 mm Hg or more.^[2] Obstruction starts at 30 mm Hg. I would not use dobutamine.^[2][1]

Branch C — Sudden-death risk

Examiner: Five years later she no longer swims competitively. Her wall is 24 mm, she has had an unexplained faint and Holter shows NSVT. How do the two guidelines approach an ICD?

Strong answer: ESC 2023 starts with the HCM Risk-SCD estimate in patients aged 16 or more. ESC says the models should not be used in elite athletes (she no longer competes) or in individuals with metabolic or infiltrative diseases or syndromes. I would want to be confident she has none of these before relying on the estimate. The models are also not validated before and after myectomy, which she has not had. Its seven inputs are age, maximal wall thickness, LA diameter, LVOT gradient (not exercise-induced), family history of SCD, NSVT and unexplained syncope.^[2][4] AHA/ACC 2024 starts with major risk factors: recent syncope suspected to be arrhythmic is one, so her faint counts if it was recent and is judged arrhythmic, and for adults with one or more it is reasonable to offer an ICD (COR 2a). In adults, NSVT is not among the major risk factors the AHA/ACC COR 2a row lists. In select adults without a major factor after clinical assessment, or when the ICD decision remains otherwise uncertain, NSVT on ambulatory monitoring or extensive LGE on CMR makes an ICD something that may be considered (COR 2b).^[28] With one or more major factors, discussing the estimated 5-year sudden death risk and mortality rates can be useful in shared decision-making about an ICD (COR 2a), and prespecified risk thresholds should not be the sole arbiter.^[28][1]

Examiner: Her HCM Risk-SCD estimate is 7%. What does that number mean?

Strong answer: ESC 2023 says an ICD should be considered at an estimated 5-year risk of 6% or more after detailed clinical assessment (Class IIa). That assessment covers the lifelong risk of complications, competing mortality from the disease and comorbidities, and the impact on lifestyle, socio-economic status and psychological health.^[2] The same cut-off defined high risk in the 2014 ESC guideline.^[20] In the external-validation complete-case analysis (n=2147), patients with a predicted risk of 6% or more had an observed 5-year SCD incidence of 8.9%, and about 13 ICDs at that level could potentially save one patient.^[19] Had she been under 16, I would use HCM Risk-Kids instead.^[2][21]

Examiner: And CMR shows LGE of 18% of LV mass?

Strong answer: For AHA/ACC, extensive LGE is not among the major risk factors listed for adults; in select adults without a major factor after clinical assessment, or when the ICD decision remains otherwise uncertain, it makes an ICD something that may be considered (COR 2b).^[28] For ESC, in the low-risk category (below 4%), extensive LGE (15% or more) may be considered in shared decision-making about a prophylactic ICD, acknowledging the lack of robust data on how scar quantification alters the HCM Risk-SCD estimate (Class IIb).^[2] In 1293 HCM patients referred for CMR and followed for a median of 3.3 years, each 10% increase in LGE carried an adjusted hazard ratio of 1.46 for SCD events.^[14]

Branch D — Escalating drug therapy

Examiner: At 30 she has a provoked gradient of 80 mm Hg and NYHA III symptoms on a maximal beta-blocker. What next?

Strong answer: For persistent LVOTO symptoms that interfere with everyday activity or quality of life despite a beta-blocker or non-dihydropyridine CCB, AHA/ACC 2024 gives COR 1 to adding a myosin inhibitor (adults only), 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. Titrated to the maximum tolerated dose with echocardiographic LVEF surveillance, mavacamten should be considered in addition to a beta-blocker (or, if this is not possible, verapamil or diltiazem) to improve symptoms in adults with resting or provoked LVOTO (Class IIa). In the absence of evidence to the contrary, ESC advises that it should not be used with disopyramide.^[2] ESC also recommends adding disopyramide, titrated to the maximum tolerated dose with QTc monitoring during up-titration (dose reduced if QTc exceeds 500 ms), to the beta-blocker (Class I) as the alternative at this step; mavacamten is Class IIa.^[2] If she remains in NYHA III–IV with a gradient of 50 mm Hg or more despite maximum tolerated drug therapy (including the disopyramide or mavacamten step), she would meet the ESC Class I recommendation for septal reduction therapy.^[2] In EXPLORER-HCM, 37% on mavacamten versus 17% on placebo met the primary pVO2-plus-NYHA composite endpoint over the 30-week treatment period.^[5] In SEQUOIA-HCM, aficamten raised peak oxygen uptake at 24 weeks by 1.7 ml/kg/min more than placebo.^[8] In MAPLE-HCM, aficamten monotherapy was superior to metoprolol monotherapy for change in peak oxygen uptake at 24 weeks (between-group difference 2.3 ml/kg/min).^[9]

Examiner: Would you use mavacamten if she had nonobstructive HCM?

Strong answer: In ODYSSEY-HCM, mavacamten did not improve either primary end point (peak oxygen uptake, KCCQ clinical summary score) significantly more than placebo at 48 weeks in nonobstructive HCM.^[10] Mavacamten is contraindicated in pregnant women because of potential teratogenic effects (AHA/ACC COR 3: Harm).^[1]

Branch E — AF and the family

Examiner: She develops paroxysmal AF at 34 with a CHA2DS2-VASc of 1. Anticoagulate?

Strong answer: Yes. ESC 2023 recommends oral anticoagulation, unless contraindicated, in all patients with HCM and AF or atrial flutter (Class I), noting that retrospective evidence suggests CHA2DS2-VASc may perform suboptimally for stroke prediction in HCM. AHA/ACC makes a DOAC (or alternatively warfarin) the default irrespective of the score.^[2][1]

Examiner: And her children?

Strong answer: HCM is autosomal dominant in most cases: if she carries a disease-causing variant, each child has a 50% chance of inheriting it.^[1] If the family is genotype-positive or has early-onset disease, AHA/ACC screens at-risk asymptomatic, phenotype-negative children with ECG and echo from the time of diagnosis in the family, repeating every 1–2 years; other at-risk asymptomatic children start no later than puberty and repeat every 2–3 years. Children who test negative for the familial variant on cascade testing can be released from surveillance. Intervals may be modified, for example if symptoms develop or the family has a malignant clinical course.^[1] AHA/ACC regards ongoing screening of genotype-positive, phenotype-negative relatives of all ages as important.^[1] In a retrospective analysis of sarcomere variant carriers without HCM at first screening, estimated penetrance at 15 years of follow-up was 46%.^[18]