Definition and diagnosis

These recommendations are not limited to asymmetric septal HCM (formerly called ‘idiopathic’), and the authors have deliberately chosen to place them in a practical context. The discovery of HCM must be based on clinical and echocardiographic findings, and in the absence of load conditions that could explain this hypertrophy. The ESC Task Force has extended the definition to all potential HCM, but expanding the aetiologies and thus the diagnostic spectrum has made readability more difficult. However, these recommendations appear more suited to routine clinical practice.

The main aetiologies are: sarcomeric HCM (by mutations in cardiac sarcomere protein genes), which represents 40–60% of conventional forms of HCM; unknown causes (25–30%); and genetic or non-genetic causes (5–10%) (i.e. metabolic disorders, mitochondrial cardiomyopathies, neuromuscular disease, malformation syndromes, infiltrative disease, endocrine disorders, heart disease and chronic use of drugs [anabolic steroids, hydroxychloroquine, etc.]).

In adults, HCM is defined by a wall thickness ≥ 15 mm (>13 mm in first-degree relatives) in one or more left ventricular (LV) myocardial segments, whatever the imaging technique (echocardiography, cardiac magnetic resonance [CMR] or computed tomography), without any explained loading conditions. In children, the diagnosis of HCM requires an LV wall thickness more than two standard deviations greater than the predicted mean. Diagnosis of HCM is based on a careful analysis of the baseline assessment (age, family history, clinical examination, electrocardiogram [ECG] and echocardiography), leading to the realisation of other examinations (imaging, biology, genetic testing) and the eventual suggestion of specific aetiologies. In neonates and children, inherited metabolic disorders and congenital dysmorphic syndromes should be considered, whereas in subjects aged > 65 years, amylose becomes a more likely cause. The clinical examination may suggest some aetiologies (e.g. gait disturbance for Friedreich’s ataxia, learning difficulties and mental retardation for mitochondrial diseases, Noonan syndrome or Danon disease and angiokeratomata for Fabry disease). Concerning ECG abnormalities, a short PR interval suggests storage diseases (Pompe disease, PRKAG2 and Danon disease) and mitochondrial disorders. Several biomarkers should be measured in routine practice (creatine kinase; renal and liver function tests; haematology tests). Alpha galactosidase A may be of interest in men aged > 30 years (Fabry disease).

Assessment of symptoms, severity and risk of progression

Echocardiography is the gold standard for the diagnosis and assessment of HCM; it comprises the measurement of LV wall thickness at end-diastole, preferentially in short-axis views. The presence or absence of a left ventricular outflow tract (LVOT) obstruction must be assessed at rest and during physiological provocation, such as the Valsalva manoeuvre. The threshold remains at 30 mmHg for the instantaneous peak Doppler LV outflow tract pressure gradient at rest, and exercise echocardiography is not recommended in asymptomatic patients with a gradient > 50 mmHg at rest. The use of contrast echocardiography is of interest when the apex is poorly visualized by ultrasound (and/or in substitution of CMR), and it may also be performed in septal alcohol ablation. Transoesophageal echocardiography is only reserved for patients who are going to have a myomectomy or in patients with poor transthoracic echocardiography windows.

CMR is the reference imaging examination, but must be performed and interpreted by trained teams experienced in cardiac imaging and in the evaluation of heart muscle disease. Delayed enhancement can assess fibrosis, but CMR is especially recommended in terms of accurate visualization of anatomical abnormalities and/or evaluation of morphology and ventricular function. However, the prognostic value of CMR is not clear; late enhancement is common in HCM and there is insufficient evidence to give it real decision-making power regarding the implantation of an implantable cardioverter defibrillator (ICD).

Exercise testing is useful for the assessment of functional capacity, potential occurrence of arrhythmia and blood pressure profile, but also the appearance of the gradient and its exercise tolerance. Cardiopulmonary exercise testing with simultaneous measurement of respiratory gases is recommended for very symptomatic patients or for the assessment of exercise intolerance. Patients with typical angina on exertion should be considered for invasive or computed tomography coronary angiography.

The occurrence of syncope should lead to a consultation, with an ECG, an upright exercise test and 48-hour ambulatory ECG monitoring; in patients with recurrent episodes of unexplained syncope, an implantable loop recorder should be considered. The occurrence of palpitations should lead to a 48-hour Holter ECG. Electrophysiological testing is not recommended for risk stratification or for the exploration of syncope; testing is indicated for the assessment of persistent or recurrent supraventricular tachycardia, for ventricular pre-excitation or for sustained monomorphic ventricular tachycardia.

Genetic counselling and family screening

Genetic counselling is recommended for all patients with HCM (whatever the familial context), unless an acquired cause has been demonstrated. The counselling should be performed by a professional trained for this specific task, and should deal with information about the genetic origin of HCM and the various implications it may have for the patient and the whole family, including modalities for optimal medical screening and follow-up in the family.

Genetic testing is recommended in the proband (the first patient diagnosed for HCM within the family) to enable cascade genetic screening of the relatives. Genetic testing should be performed in certified diagnostic laboratories with expertise in that field. Post-mortem analyses might be considered if the proband is deceased and tissue has been stored. When a causative mutation is identified in the proband, then predictive genetic testing is recommended in first-degree relatives, after careful pre-test counselling, to guide the cardiac management of these relatives.

Relatives who do not carry the mutation can be discharged from further follow-up, whereas relatives who carry the mutation will benefit from a cardiac evaluation and follow-up. If no causative mutation was characterised in the proband with HCM, then family screening is solely based on cardiac screening with ECG and echocardiography, which should be considered in first-degree relatives aged ≥ 10 years, and should be repeated every 1 or 2 years between 10–20 years of age and every 2 or 5 years thereafter, as delayed cardiac expression of HCM is observed quite often, even in adults.

For the situation of a mutation carrier without cardiac expression (preclinical phase of HCM), the guidelines mention that sporting activity may be allowed, taken into account the type of sport, the underlying mutated gene and the results of regular and repeated cardiac examinations.