**4.2 Arrhythmia**

*Sudden Cardiac Death*

**3.3 Family history**

**3.4 Genetic testing**

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.

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.

Heart failure management should be in accordance with guidelines, such as those of the ESC, which are summarized below [1]. An angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is indicated in left ventricular systolic dysfunction. If symptomatic, i.e. New York Heart Association functional classification (NYHA-class) 2 or above, a beta-blocker should be added to treatment with the ACEi/ARB. In patients who remain symptomatic with systolic

**4. Clinical management of dilated cardiomyopathy**

**174**

**4.1 Heart failure**

There is an increased risk for both brady- and tachyarrhythmia in DCM, these arrhythmias can also be a contributing factor worsening heart failure. In symptomatic sinus node disease or in high-degree atrioventricular (AV)-block without a reversible cause a pacemaker is indicated in order the relieve symptoms and/or increase survival [3]. Beta-blockers are often indicated for the treatment of symptomatic heart failure but also have antiarrhythmic properties making it useful for both rhythm and rate control. With the exception of beta-blockers currently available antiarrhythmic drugs have not consistently been shown in randomized clinical trials to improve survival in the primary management of arrhythmia. Amiodarone have shown some positive results and is highly useful to control symptoms, to terminate tachyarrhythmia and prevent recurrence [3]. In heart failure with reduced ejection fraction most other antiarrhythmic agents are contraindicated, this includes flecainide and dronedarone otherwise frequently used for rhythm control in atrial fibrillation [3].

#### **4.3 Prevention of sudden cardiac death**

An implantable cardioverter defibrillator (ICD) is an effective way to prevent sudden cardiac death in those at risk for developing ventricular tachycardia or ventricular fibrillation [3]. An ICD offers both antitachycardia pacing, rapid ventricular pacing (preferably bursts), that can terminate ventricular tachycardia, as well as

cardioversion that effectively terminate ventricular tachycardia and ventricular fibrillation. In addition, an ICD also functions as a bradycardia pacemaker and in combination with a left-ventricular lead it can offer cardiac resynchronization therapy.

The ESC recommends a primary prophylactic ICD for patients with symptomatic heart failure (NYHA-class II-III), left ventricular systolic ejection fraction ≤35% despite at least three months of optimal medical therapy and a life expectancy of at least 1 year [3]. The recommendation is class I (is recommended) for both heart failure due to ischemic heart disease as well as nonischemic cardiomyopathy. The level of evidence is considered stronger for heart failure with ischemic etiology (level A) than for nonischemic etiology (level B) [3]. In the SCD-HeFT trial an ICD reduced all-cause mortality as well as sudden cardiac death in patients with reduced ejection fraction [16]. In the DEFINITE trial, with a study population of patients with heart failure due to nonischemic etiology, sudden cardiac death was reduced by 80%, however reduction in all-cause mortality did not reach statistical significance (hazard ratio 0.65, p = 0.08) [17]. In 2016, the DANISH trial randomized participants with heart failure of nonischemic origin to either an ICD or otherwise optimal medical management (both groups were eligible for cardiac resynchronization therapy), after 5 years there was a significant reduction in sudden cardiac death (HR; 0.50, p = 0.005) [18]. For the whole group no significant reduction was seen in all-cause mortality (HR; 0.87, p = 0.28), however subgroup analysis of patients younger than 68 years showed a reduction all-cause mortality (hazard ratio 0.64; p = 0.01) [18]. This caused uncertainty about whether patients with heart failure of nonischemic etiology should receive ICDs on the same indications as those with ischemic etiology. Since then, a meta-analysis of six trials, that included DANISH, has showed that ICD on primary-prevention indication in patients with heart failure of nonischemic etiology reduced all-cause mortality (hazard ratio 0.76, p = 0.001) [19]. An analysis of the Swedish Heart Failure Registry revealed a 27% relative risk reduction in all-cause mortality after 1 year, this was consistent in both the subgroup with ischemic and with nonischemic etiology [20]. We have previously published a retrospective observational study of our ICD-cohort [21]. In our study 236 patients with primary prevention ICD due to heart failure of ischemic (61.9%) or nonischemic (38.1%) etiology were included, there was no difference in cumulative risk for appropriate therapy between the groups (Mantel-Cox p = 0.985) [21]. The guidelines of the ESC recommending implantation of a primary prevention ICD should therefore be followed in patients with heart failure with both ischemic etiology as well as nonischemic DCM [3].
