**3.1 Echocardiography**

*Sudden Cardiac Death*

**2. Definitions**

**2.1 Cardiomyopathies**

Definitions of cardiomyopathies differ over time and between clinical traditions. While in the future cardiomyopathies might be classified after causative mutations, they have traditionally been classified by phenotype and cardiac morphology, e.g. DCM or hypertrophic cardiomyopathy (HCM). This system of classification has the

advantage that the phenotype is most often known prior to the genotype.

non-genetic forms of cardiomyopathy (**Figure 1**) [2].

conditions (hypertension, valve disease) [2].

**2.2 Dilated cardiomyopathy**

Originally, cardiomyopathies were considered distinct primary myocardial disorders of unknown etiology, whereas heart muscle disorders of known etiology or caused by systemic disease were classified as secondary or specific heart muscle disease. In 2006 the American Heart Association proposed a classification that defined cardiomyopathies either as primary or secondary, referring either to a disease were the heart is the sole or primarily affected organ, alternatively where myocardial involvement is part of a systemic disease [7]. However, in 2008, the European Society of Cardiology (ESC) proposed an alternate classification in which a cardiomyopathy is defined as "a myocardial disorder in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality". Furthermore, the ESC subdivides cardiomyopathies depending on morphology and function as well as based upon inheritance pattern; distinguishing between familial or genetic forms versus non-familial or

DCM is a distinct cardiomyopathy and a common cause of heart failure defined by dilatation of the left ventricle and reduced ejection fraction [2]. In later phases dilation of the right ventricle and the atria is often seen, however this is not required for diagnosis. For the diagnosis of DCM, the reduction in global systolic function should not solely be attributable to coronary artery disease or abnormal loading

*Classification of cardiomyopathies proposed by the European Society of Cardiology [2]. Cardiomyopathies are primarily classified according to morphology and function, then based on whether the disease is familial or non-familial, and lastly depending on either known disease causing mutation or pathophysiological* 

**172**

**Figure 1.**

*mechanism.*

Diagnostic evaluation for suspected heart failure should be managed in accordance with guidelines, such as those of the ESC [1]. Echocardiography constitutes a cornerstone of the evaluation and is readily available. For the diagnosis of DCM both left ventricular systolic dysfunction, as well as dilatation of the left ventricle, needs to be present and not explained by coronary artery disease or abnormal loading conditions (hypertension, valve disease) [9]. Left ventricular systolic dysfunction is defined as abnormal left ventricular systolic ejection fraction measured with any modality, preferentially echocardiography or cardiac magnet resonance tomography. Left ventricular dilatation (**Figure 2**) is defined as left ventricular end-diastolic volumes or diameters >2 standard deviations according to nomograms (Z > 2 standard deviations) after correction for body surface area and age, or body surface area and sex [9].

#### **3.2 Cardiac magnetic resonance tomography**

Cardiac magnetic resonance tomography is valuable as a complement to echocardiography. It allows for a better evaluation of the whole myocardium including the right ventricle and septum which provides aid in ruling out other cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and HCM. Myocarditis has been identified as a cause of acquired forms of DCM [10]. Cardiac magnetic resonance can be used to assess the presence of active myocarditis as well as scar tissue that could indicate previous episodes of myocarditis. Cardiac magnetic resonance imaging is, according to the ESC, indicative of active myocarditis if it, in the setting of clinically suspected myocarditis, fulfills 2 out of 3 Lake Louise criteria [11]. These criteria include; high signaling on T2-weighted images (indicative of edema), early gadolinium enhancement (indicative of increased blood flow), and late gadolinium enhancement (indicative of scar tissue) [11].

#### **Figure 2.**

*Echocardiography with apical four chamber view showing spherical dilatation of the left ventricle. Image adapted from Jamil et al. [12]. Published by IntechOpen under open access https://creativecommons.org/licenses/by/3.0/.*

### **3.3 Family history**

Of particular importance is a family history of cardiomyopathy, arrhythmia or sudden cardiac death. If another family member also fulfills the criteria for DCM the patient can be said to have familial DCM [8]. A pedigree, a family tree, could be drawn to visualize what family members are affected by the disease or certain symptoms as well as how they are related to each other. By doing this the type of inheritance pattern can often be discerned, see Section 5.1. Inheritance patterns.

### **3.4 Genetic testing**

Genetic testing requires knowledge about genetics, the disease in question, as well as legal and ethical considerations. It is important that the patient is the one who makes an informed decision about if a gene test should be performed [13]. It is also important to be aware of what the benefits and potential detriments of a genetic test are. The current ESC Heart failure guidelines from 2016 recommend that genetic testing should be performed in accordance with the ESC position statement on genetic counseling and testing in cardiomyopathies from 2010 [1, 13]. Most genotypes cannot be distinguished from each other by evaluation of the phenotype. Due to this broad gene panels are required that incorporate most known definite and putative DCM genes. The ESC states that the main role of genetic testing is in patients with an already confirmed diagnosis of idiopathic DCM (where acquired causes has been ruled out) to enable genetic testing of first degree-relatives and possibly cascade screening, see Section 5.2. Family screening. They caution against the use of genetic testing to establish the diagnosis of a cardiomyopathy in borderline cases except for in the setting of expert teams after detailed clinical and family assessment. In definite DCM most often, the exact gene affected do not change the clinical management of that individual patient. However, in some cases of DCM with red flags such as simultaneous conductions disorders indicative of a specific phenotype, genetic testing can be used to establish a specific genetic diagnosis. In patients with mutations in LMNA that causes DCM, genetic diagnosis might affect the clinical management. It should be noted that negative genetic tests do not rule out that the cardiomyopathy is familial or genetic. The interpretation of genetic tests is time consuming, complicated, and often not conclusive. When the ESC position statement was written in 2010 genetic tests had been mainly used for research purposes and had recently become available for clinicians. Genetic tests have today become more affordable and available. The current trend is towards more genetic evaluations being conducted and it is our opinion that this trend should continue. More patients with DCM receiving a genetic diagnosis will over time improve knowledge of the different genotypes. In order to offer equal health care genetic testing must be conducted even outside the setting of tertiary centers.
