Cardiomyopathy hypertrophic I42.1; I42.2

Liouville and Hallopeau, 1869

Most frequent genetic (90% of cases), autosomal dominant inherited, less frequently sporadic heart disease in which the heart weight is increased to 2-3 times the norm, with hypertrophy of the ventricular walls and the septum with rather small ventricular lumen.

Incidence 19/100,000 per year; prevalence: 1/500; m: w=1:1; This makes HCM the most common heart disease caused by a genetic defect.

Large heterogeneous variability (> 1400 mutations in >27 gene loci). Mutations primarily affect genes encoding proteins of the cardiac sarcomere. 2/3 of all mutations affect MYH7 (chromosome 14q12 - encodes beta-myosin heavy chain), about 35% of cases, MYBPC3 (chromosome 11p11.2 - encodes myosin-binding protein C), about 30% of cases, and TNNT2 (chromosome 1q32 - encodes troponin T), about 15% of cases. Further affected are TPM1 (alpha-tropomyosin), TNNI3 (troponin I), ACTC (actin), KLHL24 (=member of the Kelch-like protein family, which act as substrate-specific adaptors for cullin E3 ubiquitin ligases. This results in accumulations of desmin intermediate filaments), among others.

A clear genotype/phenotype correlation has not yet been established.

Many patients have no or only mild clinical symptoms. When symptoms occur, they are auscultatorily similar to the systolic expulsion sound of aortic stenosis.

Hypertrophic cardiomyopathy is characterized by a mostly asymmetrical thickening (hypertrophy) of the muscles of the left ventricle. In some cases there is an increasing constriction (obstruction) of the left ventricular outflow tract under stress (hypertrophic obstructive cardiomyopathy, HOCM) and in the course of the disease a stiffening (with reduced elasticity) of the heart muscle (compliance disorder).

The resulting hypertrophy is distributed differently in the ventricle:

• General hypertrophy (hypertrophic non obstructive cardiomyopathy)
• Hypertrophy of the septum in the region of the outflow tract with obstruction of the outflow tract (hypertrophic obstructive cardiomyopathy, HOCM)
• Hypertrophy that mainly affects the tip of the heart (apical hypertrophic cardiomyopathy)

In all forms, hypertrophy leads to diastolic dysfunction with obstruction of ventricular filling and congestion in the pulmonary venous system. In hypertrophic obstructive cardiomyopathy, mitral insufficiency continues to occur.

Main complaints are stress dyspnea, palpitations and syncope. Auscultatory: Occurrence of a systolic murmur and a 3rd heartbeat possible. In children, the occurrence of pectanginous complaints should be a reason for regular checks for HCM. Children are asymptomatic for a long time and may die suddenly. The earlier the symptoms occur, the less favourable the prognosis.

Clinic (see above)

Auscultation: In HOCM late systolic spindle-shaped noise, amplified by physical exertion.

ECG: signs of left hypertrophy, pseudo infarct images, ventricular arrhythmias.

Echocardiography: The septum ventriculorum is often thickened more than the posterior wall of the left ventricle. Ratio of septum thickness to free wall (S: P) >1.3:1 up to extreme values of >3:1. This asymmetric septal hypertrophy (>13mm) occurs in 90% of cases and typically affects either the entire trabecular septum or its subvalvular, middle or apical part. More rarely, the hypertrophy is located on the mid-ventricular left free wall or apical. In children the diagnosis based on septal hypertrophy is more problematic because the septum may be physiologically thickened in developing hearts.

MRI: pressure gradient, anatomy and function of the heart. Late recording of gadolinium on MRI as an expression of extensive fibrosis (>15% of myocardium).

Myocardial biopsy: The histological image is not specific. Branching disorders of the hypertrophied heart muscle cells (diameters around 4o µm) are conspicuous with the absence of the normal parallel arrangement due to increased lateral branching. Furthermore, bizarre and enlarged nuclei with perinuclear yard as well as partially present duplex nuclei. Conspicuous disorganization of the myocardium with angular to vertebral muscle fibers and abnormal side-to-side connection. To be able to diagnose HCM, the disorganization must cover >5% of the tissue.

Cardiomyopathies of other genesis

• Hypertensive heart disease(arterial hypertension)
• Exclusion of aortic stenosis
• Storage diseases(Fabry's disease, amyloidosis)
• In patients > 55 years, exclusion of transthyretin amyloidosis
• Other genetic neurogenic disorders (e.g. Noonan syndrome: with dwarfism, deep hairline in the neck, café-au-lait spots. Non-obstructive hypertrophic cardiomyopathy sometimes much more pronounced)

Avoid heavy physical strain.

Administration of calcium antagonists. Otherwise, symptomatic therapy.

Percutaneous transluminal septal myocardial ablation (PTSMA): Triggering of localized septal myocardial necrosis by targeted alcohol injection.

Transaortal subvalvular myectomy (TSM): well documented prognosis improvement. Excess muscle tissue in the outflow tract of the left ventricle is removed through the aortic valve. Success rate and risks are similar to alcohol ablation, but the procedure is much more invasive.

Heart transplantation (TX): in patients with dilated course (NYHA III and NYHA IV)

Annual mortality rate in unselected adult patients at about 1%. Presence of ventricular arrhythmias. Especially frequent in juvenile patients with tropinin T mutations (TNNT2 gene).

HCM in its auscultatory silent form is one of the most common causes of sudden cardiac death in young athletes!

1. Battegay E (2017) Differential diagnosis of internal diseases. Georg Thieme Publisher p.273
2. Salman OF et al (2018) Inherited Cardiomyopathies and the Role of Mutations in Non-coding Regions of the Genome. Front Cardiovasc Med 5:77.
3. Towe EC et al. (2015) Genotype-Phenotype Correlations in Apical Variant Hypertrophic Cardiomyopathy. Congenit Heart Dis 10: E139-145.