**3. Conclusion**

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

B [66, 77, 83, 84].

*2.7.3 Arrhythmias*

follow-up. At present, there are no trial data to guide anticoagulant treatment regime in DCM. Due to two studies (WATCH and WARCEF trial) showing a slight advantage of warfarin over aspirin, anticoagulation with warfarin is advised in patients with a history of thromboembolism or evidence of intracardiac thrombus [81, 82]. Current ACC/AHA HF guidelines do not recommend anticoagulation in reduced left ventricular function and sinus rhythm without prior thromboembolic events or known cardioembolic source [83]. Studies testing the non-vitamin K antagonist oral anticoagulants (NOACs) in patients with reduced left ventricular function are currently ongoing. In DCM patients with documented AF, oral anticoagulant is recommended with CHA2DS2-VASc score ≥ 2, as a class I indication and in men with a CHA2DS2-VASc score of 1 as class IIa with level of evidence

The most common arrhythmia in DCM is AF, which increases the risk of thromboembolic complications, impairs cardiac function and worsening HF symptoms. Therefore, evaluation of rate control and anticoagulation in order to preserve LV-function and prevent thromboembolic events is crucial. In the acute setting betablockers, digoxin and their combination may be used to control ventricular rate. In the chronic stage, rhythm control has been shown to be superior to rate control alone in reducing mortality [85]. Because of the commonly reduced left ventricular function, the only therapeutic option is type III antiarrhythmic drug such as amiodarone. Alternatively, electrical cardioversion can be performed. Recently, the CASTLE-AF study demonstrated the superiority of AF catheter ablation in certain patients with HF as compared to medical therapy. The ablation was associated with a significantly lower rate of death and hospitalization for worsening HF [86]. DCM patients may suffer from ventricular arrhythmias (VA), which are mainly caused by myocardial damage, fibrosis and/or loss of cell-to-cell conjunctions, that are described by three mechanisms: reentry, trigger activity, and automatism [87]. Monomorphic ventricular tachycardias (VTs) are frequently induced by macro-reentry mechanism, which is best treated by ablation. The main trigger mechanisms are electrolyte imbalance, mostly secondary to diuretic treatment, antiarrhythmic drugs, and bradycardia. The therapeutic options are a combination of antiarrhythmic drugs like betablockers and type III antiarrhythmics and/or implantation of an implantable cardioverter defibrillator (ICD). The

Although there has been a significant improvement in prognosis of DCM patients over the last decades, mortality is still high. The prognosis is mainly influenced by HF symptoms and more relevant by the appearance of VTs. Survival data of adults with DCM have shown a one-year mortality of 25–30% and a 50% survival at 5 years. Sustained VT or VF presents the main cause for SCD, which occurs in up to 12% of DCM patients [4, 88]. In general, the prevalence of sustained VT (monomorphic or polymorphic) is estimated as less than 5% [89]. Recently, the Pediatric Cardiomyopathy Registry presented a 5-year incidence rate of SCD in children with DCM of 3% [90]. An age at diagnosis below 14 years, LV dilation, and posterior wall thinning were identified as the most important risk factors. In contrast, the mortality in adults is mostly associated with age and male gender, reduced New York Heart Association (NYHA) functional class, impaired LVEF, and the presence of specific cardiac biomarkers as well as myocardial fibrosis in CMR [91–94]. Furthermore,

indications for ICD treatment are described later [4].

**2.8 Prognosis and risk stratification**

**52**

DCM includes a heterogeneous group of myocardial and systemic conditions causing left ventricular dilatation and dysfunction. DCM is one of the most common cardiomyopathies worldwide. Yet, the real prevalence is unknown. The etiology contains non-genetic (e.g. myocarditis, peripartum, toxics, arrhythmia, infiltrative etiologies, endocrine, nutritional, and neuromuscular) and genetic causes. Literature on genetic mutations being responsible for DCM has increased exponentially. Today, up to 30% of the DCM cases are described to be caused by a gene mutation, the majority of which occur in autosomal genes that encode for a wide range of proteins of the cardiomyocyte's structural elements. Mutations in genes encoding sarcomeric, cytoskeletal, desmosomal, nuclear membrane, mitochondrial, and RNA-binding proteins have all been linked to DCM. However, the most common mutations occur in genes encoding sarcomeric proteins and in genes related to the nuclear envelope and the
