Perspective:

The following are points to remember about the European Society of Cardiology guidelines on hypertrophic cardiomyopathy (HCM):

1. In a majority of cases, HCM is caused by mutations in the genes encoding beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3); less commonly affected genes include cardiac troponin I and T (TNNI3, TNNT2), tropomyosin alpha-1 chain (TPM1), and myosin light chain 3 (MYL3). In general, patients with a sarcomere protein mutation present earlier and report a higher prevalence of family history of HCM and sudden cardiac death than those without a mutation. A majority of cases are inherited as an autosomal dominant genetic trait with a 50% risk of transmission to offspring.

2. The diagnosis of HCM is based on the detection of increased left ventricular (LV) wall thickness unexplained by loading conditions. In adults, the diagnosis of HCM is based on wall thickness ≥15 mm in one or more segments measured by any imaging technique (echocardiography, cardiac magnetic resonance [CMR] imaging, or computed tomography [CT]). For wall thickness of 13-14 mm, a diagnosis of HCM requires evaluation of other features (including family history, electrocardiogram [ECG] abnormalities, and other testing).

3. On echocardiography, approximately one third of patients with HCM have mitral leaflet systolic anterior motion (SAM) that results in left ventricular (LV) outflow obstruction (defined as peak instantaneous outflow gradient ≥30 mm Hg) at rest, and another third have outflow obstruction only during maneuvers that alter loading conditions and contractility. Other features that contribute to LV outflow obstruction include papillary muscle abnormalities (hypertrophy, anterior and internal displacement, direct insertion onto the anterior mitral leaflet) and mitral leaflet abnormalities (elongation or accessory tissue).

4. CMR imaging can be used to detect LV hypertrophy and evidence of outflow obstruction, similar to echocardiography; late gadolinium enhancement on CMR correlates with myocardial fibrosis, suggestive of expansion of the myocardial interstitium.

5. Genetic testing is recommended in patients fulfilling diagnostic criteria for HCM when it enables cascade screening of relatives (Class I, Level of Evidence B); to confirm a diagnosis in the setting of symptoms and signs suggestive of a specific cause of HCM (Class I, Level of Evidence B); in patients with a borderline diagnosis of HCM, but only after detailed assessment by specialist teams (Class IIa, Level of Evidence C); and post-mortem, to enable cascade screening of relatives (Class IIa, Level of Evidence C).

6. Additional diagnostic testing is indicated:
a) Coronary angiography is recommended in adult survivors of cardiac arrest, with sustained ventricular tachyarrhythmia (VT), and in patients with severe stable angina (Class I, Level of Evidence C); invasive or CT coronary angiography should be considered in patients with typical exertional chest pain and intermediate pretest probability of coronary disease, and in patients ≥40 years of age considered for septal reduction therapy (Class IIa, Level of Evidence C).

b) Invasive assessment of intracardiac pressures is recommended in patients considered for heart transplantation (Class I, Level of Evidence B), and in symptomatic patients with inconclusive noninvasive cardiac imaging (Class IIb, Level of Evidence C).

c) Cardiopulmonary exercise testing with measurement of respiratory gases is recommended in severely symptomatic patients evaluated for heart transplantation (Class I, Level of Evidence B); regardless of symptoms, to assess the severity and mechanism of exercise intolerance and systolic blood pressure change (Class IIa, Level of Evidence B); and to determine the severity of exercise limitation among symptomatic patients undergoing consideration for alcohol septal ablation or septal myectomy (Class IIa, Level of Evidence C).

d) Electrophysiology testing is recommended in patients with documented persistent or recurrent supraventricular tachycardia and in patients with ventricular pre-excitation (Class I, Level of Evidence C); in selected patients with symptomatic monomorphic, sustained VT (Class IIb, Level of Evidence C); but not for stratification of sudden death risk (Class III, Level of Evidence C).

7. LV outflow obstruction can be treated:
a) Medically. Non-vasodilating beta-blockers, titrated to maximum tolerated dose, are the first line of therapy to improve symptoms (Class I, Level of Evidence B); verapamil, titrated to maximum tolerated dose, is recommended to improve symptoms in patients intolerant to beta-blockers (Class I, Level of Evidence B); disopyramide, titrated to the maximum tolerated dose, is recommended in addition to a beta-blocker (or verapamil) to improve symptoms (Class I, Level of Evidence B).

b) Septal reduction therapy. Septal reduction therapies should be performed by experienced operators working as part of a multidisciplinary team (Class I, Level of Evidence C); septal reduction therapy to improve symptoms is recommended in patients with resting or provoked peak outflow gradient ≥50 mm Hg and New York Heart Association class III-IV symptoms despite maximum tolerated medical therapy (Class I, Level of Evidence B); septal reduction therapy should be considered in patients with recurrent exertional syncope and resting or provoked peak outflow gradient ≥50 mm Hg despite optimal medical therapy (Class IIa, Level of Evidence C); septal myectomy rather than alcohol septal ablation is recommended if there is an indication for septal reduction therapy and there is another lesion requiring surgical intervention (Class I, Level of Evidence C); mitral valve repair or replacement should be considered in symptomatic patients with resting or provoked peak outflow gradient ≥50 mm Hg and moderate to severe mitral regurgitation not caused by mitral leaflet SAM (Class IIa, Level of Evidence C); mitral valve repair or replacement may be considered in patients with resting or provoked peak outflow gradient ≥50 mm Hg and maximal septal thickness ≤16 mm or when there is moderate to severe mitral regurgitation following isolated myectomy (Class IIb, Level of Evidence C).

c) Pacing. Sequential atrioventricular (AV) pacing may be considered in selected patients with resting or provoked peak outflow gradient ≥50 mm Hg, sinus rhythm and drug-refractory symptoms, who have a contraindication to septal reduction therapy (Class IIb, Level of Evidence C). A dual-chamber implantable cardioverter-defibrillator (ICD) may be considered in patients with resting or provoked peak outflow gradient ≥50 mm Hg, sinus rhythm, and drug-refractory symptoms, who have an indication for ICD.

8. Features associated with an increased risk of sudden cardiac death include younger age, nonsustained VT (≥3 beats at ≥120/min lasting <30 seconds), maximum LV wall thickness ≥30 mm, family history of sudden cardiac death, syncope, left atrial diameter, LV outflow obstruction, and an abnormal exercise blood pressure response among patients ≤40 years.

9. Routine follow-up is recommended as follows: clinical evaluation including ECG and echocardiography every 12-24 months in clinically stable patients or if there is a change in symptoms (Class I, Level of Evidence C); 48-hour ambulatory ECG every 12-24 months in stable patients, every 6-12 months in sinus rhythm, and left atrial size ≥45 mm, or with new palpitations (Class I, Level of Evidence C); exercise testing every 2-3 years in stable patients or every 1 year if progressive symptoms (Class IIa, Level of Evidence C); cardiopulmonary exercise testing every 2-3 years in stable patients or every 1 year with progressive symptoms (Class IIb, Level of Evidence C); and CMR every 5 years in stable patients or every 2-3 years if progressive disease (Class IIb, Level of Evidence C).