**2. Dilated cardiomyopathy: a frequent cardiac disease**

### **2.1 Definition**

In 1980, the World Health Organization (WHO) defined cardiomyopathies as "heart muscle diseases of unknown cause" [6]. The definition was established to distinguish cardiomyopathies from cardiac diseases with known entities such as hypertension, ischemic, or valvular heart disease. About 15 years later, the WHO/ International Society and Federation of Cardiology (ISFC) Task Force classified cardiomyopathies according to anatomy and physiology into dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and unclassified cardiomyopathies. The definitions and classifications of cardiomyopathies changed over the years. The American Heart Association (AHA) presented a new scheme in 2006 that combined genetic and clinical criteria [7]. In contrast to that, the ESC defined in 2008 cardiomyopathies in a more clinically oriented classification system according to the WHO scheme as myocardial disorders with structurally and functionally abnormities of the heart muscle in the absence of coronary artery disease, hypertension, valvular disease, or congenital heart disease [3]. As mentioned above, right ventricular dilatation and dysfunction may be present but are not necessary for the diagnosis. Further, DCM is classified into familial/genetic and nonfamilial/nongenetic forms [3]. Recently, a revised definition of DCM was presented by the ESC working group on myocardial and pericardial diseases [8]. This position paper did not modify the above-mentioned definition, it rather added the important value of diverse etiologies and clinical manifestations with an introduction of a novel concept of a continuous phenotypic DCM spectrum, ranging from the subclinical mutation carriers to fully expressed DCM phenotypes.

#### **2.2 Prevalence**

The prevalence of DCM in the general population is unknown. The reported numbers considerably vary due to inhomogeneous study methodologies, which are mainly related to inconsistent definitions and classifications of DCM. In addition, the prevalence of DCM varies according to geographic and ethnic differences. One of the first reports was derived from an epidemiological study conducted in Olmsted County, Minnesota, from 1975 to 1984. For the diagnosis of DCM, the authors implemented echocardiography, angiography, and autopsy cases [9]. They presented a prevalence of 36.5/100,000 individuals or 1 in 2700 with a male to female ratio of 3:4 in a European-American population. A much higher prevalence with 1:250 was reported recently by a study from Hershberger et al. The authors estimated the DCM prevalence based on the known ratio of idiopathic DCM to

**41**

**Table 1.**

*Current Pathophysiological and Genetic Aspects of Dilated Cardiomyopathy*

HCM of ≈2:1. In addition, clinical data of HF patients and left ventricular dysfunction were used as a surrogate for DCM [10]. In Western countries, 25–40% of DCM patients have been described with evidence of familial DCM with predominantly autosomal dominant inheritance [4, 11–13]. In general, epidemiologic studies have stated a rate of 20 up to >50% of familial DCM in patients, who were initially

The first presentation of patients with DCM is often characterized by signs and symptoms of HF, such as dyspnea, ankle swelling, fatigue, elevated jugular venous pressure, pulmonary rales, and peripheral edema (**Table 1**). These result from reduced cardiac function with low output and/or elevated intracardiac pressures. Other clinical manifestations include chest pain caused by reduced coronary blood flow or congestion, palpitations, and syncope or sudden cardiac death (SCD). Arrhythmia results from multifactorial reasons, which are present in DCM and include structural changes with myocardial fibrosis and left ventricular dilation as well as electrophysiological changes [19]. The risk of SCD is highly heterogeneous and depends on etiologies and risk factors [20]. Some genetic constellations may be associated with arrhythmias out of proportion to the degree of left ventricular dysfunction (e.g., pathogenic variants in DES, LMNA, and SCN5A) [21]. This is described later in this chapter (see Sections 2.7.3 and 2.8). Furthermore, patients might present with pulmonary and systemic thromboembolism [22]. Possible clini-

*DOI: http://dx.doi.org/10.5772/intechopen.83567*

diagnosed with IDC [9, 11, 14–18].

cal findings are summarized in **Table 1**.

Palpitations Syncope

Tachycardia Pulsus alternans Arrhythmia Third heart sound Loud 2nd heart sound Displaced apex

beat

Elevated jugular venous pressure Eedema

*Clinical findings in dilated cardiomyopathy.*

Symptoms Chest pain

Clinical signs Hypotonia

**Cardiac Pulmonary Gastrointestinal/**

Dyspnea Wheeze Blood-tinged sputum Cough

Tachycardia Tachypnoea Low oxygen saturation Hemoptysis Rales

Obstructive lung auscultation Diminished lung sounds due to pleural effusions Pulmonary edema **urogenital**

Reduced appetite Epigastral pain Bloating Obstipation Diarrhea Swollen abdomen Nycturia Reduced libido Erectile dysfunction

Hepatomegaly Ascites

failure Cachexia

Jaundice in terminal liver

**Other**

Dizziness Lightheadness

Fatigue Fainting Sweating Leg swelling

disease Skin alterations Visual and hearing impairment Gait disturbance

Deafness Myotonia Hyperpigmentation Palmoplantar keratoderma

Woolly hair

Concentration disturbances

Symptoms of multisystem

Intellectual disability

Dysmorphic appearance Polyneuropathic symptoms Carpal tunnel syndrome

**2.3 Clinical presentation**

*Current Pathophysiological and Genetic Aspects of Dilated Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.83567*

HCM of ≈2:1. In addition, clinical data of HF patients and left ventricular dysfunction were used as a surrogate for DCM [10]. In Western countries, 25–40% of DCM patients have been described with evidence of familial DCM with predominantly autosomal dominant inheritance [4, 11–13]. In general, epidemiologic studies have stated a rate of 20 up to >50% of familial DCM in patients, who were initially diagnosed with IDC [9, 11, 14–18].
