Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterised by the presence of significant primary hypertrophy in the left ventricle (in adults ≥ 15 mm), which means that it is not caused by disorders leading to increased LV afterload (resistance to blood ejection). In clinical practice, conditions than can provoke compensatory or secondary ventricular hypertrophy are mainly hypertension and aortic stenosis.

HCM is a relatively common clinical entity with an incidence of 1 in every 500 individuals. Familial origin occurs in 50–60 % of the cases, presenting an autosomal dominant pattern of transmission in most of the cases, with incomplete penetrance.

Mutations in several genes have been identified as associated with HCM. The majority of the mutated genes encode sarcomeric proteins, which are proteins that form the contractile apparatus of the myocyte.

Clinically, it is important to highlight the great variability in symptomatology among these patients, not only in clinical presentation but also evolution and prognosis. Patients can report chest pain, dyspnoea on exertion, dizziness or syncope. The ECG usually shows a pattern of LV hypertrophy with increased voltage in the left precordial leads, I and aVL, and prominent and pathological Q waves, although deep and narrow (“dagger-like”). Alterations in the T waves and depression in the ST segment are also common. A definitive diagnosis is carried out with echocardiography by measuring the parietal thickness at different planes and projections, and discarding other clinical entities that could cause a similar degree of hypertrophy. In adults, HCM is diagnosed when the maximal wall thickness is greater or equal to 15 mm measured in end-diastole.

A small subgroup of patients have a particularly malignant course with episodes of sudden cardiac death (SCD) due to ventricular arrhythmias. In order to identify patients at higher risk, who would benefit from an automatic implantable cardiac defibrillator (ICD), a prognostic stratification should be done taking into account several risk factors associated with SD.

HCM can be considered obstructive or non-obstructive depending on the presence of obstruction of the left ventricular outflow tract (LVOTO). One third of patients with HCM have a significant obstruction (>30 mmHg) at rest and an additional third develops obstruction on exertion but not at rest. Based on the location at which hypertrophy is more manifest, HCM can be clinically divided in concentric, asymmetric with sigmoid septal contour (septal HCM), asymmetric with reverse pattern and apical forms. Gross and microscopic features are shown in Table 8.2.

Arrhythmogenic cardiomyopathy (ACM) is a condition characterised by fibrous or fibro-fatty replacement of the myocardium. ACM was initially described as arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), but during the last decade it has been demonstrated that the disease can affect both ventricles or even exclusively or predominantly the LV. A high density of ventricular arrhythmias, with varying degrees of complexity, is frequently found in patients with ACM. Characteristic features of ACM include the presence of ventricular wall thinning, associated with aneurysms preferentially located at the infundibular, subtricuspid or apical levels in the RV, or regional wall motion abnormalities in the LV.

A family history of the disease is present in approximately 50 % of patients, and inheritance shows an autosomal dominant pattern with variable expressivity and incomplete penetrance. Mutations in genes encoding desmosomal proteins constitute the most commonly found genetic defect in these patients. Desmosomes are molecular protein complexes that participate in the maintenance of cellular structure and cell-to-cell adhesions. Defects in these proteins can lead to separation between cells due to defective intercellular junctions, which can cause apoptosis and death of myocytes, and ultimately their replacement with fibrous and adipose tissue.

ACM usually debuts in adolescents and before the fourth decade of life. Clinical presentation can be very variable, from progressive heart failure to a mainly arrhythmogenic disease with cardiac arrest as the first manifestation. Ventricular arrhythmias are very common, hence the name of the disease, and can vary from isolated ventricular extrasystoles to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

ACM must be suspected in individuals suffering frequent and more or less complex ventricular arrhythmias, in patients that have had a cardiac arrest, and in those with RV dilatation non-attributab. to pulmonary disease or to a systemic-pulmonary shunt. Diagnosis may be difficult, and in the clinical practice ACM is diagnosed when the patient fulfils several major and/or minor criteria. These criteria are established depending on the degree of sensitivity, specificity and predictive value of the regional wall motion abnormalities identified through imaging techniques such as echocardiography or MRI, through ECG abnormalities, ventricular arrhythmias, familial background/genetic, and histopathological studies.

Treatment of ACM is focused on the prevention of SCD and the management of heart failure. Competitive physical exercise is contraindicated. Pharmacological treatment is initiated in patients with ventricular arrhythmias or progressive ventricular dysfunction. An implantable cardiac defibrillator could be an option for patients that have suffered a cardiac arrest, syncope, or badly-tolerated ventricular arrhythmias, and in patients with severe left or right ventricular dysfunction, as a bridge to heart transplantation. Radiofrequency ablation may diminish the occurrence and complexity of the arrhythmias suffered by these patients, although this is a transient solution.

Three forms of ACM exist depending on the ventricle involved:

The pathologic characteristics of ACM are shown in Table 8.3.