*5.1.2 Autosomal recessive*

*Sudden Cardiac Death*

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].

Most genetic mutations that cause familial DCM have an autosomal dominant inheritance pattern with variable penetrance [22]. However, autosomal recessive, X-linked recessive and mitochondrial inheritance patterns have been described [22]. Sometimes a mutation is found that does not occur in any of the parents, this is

Autosomal inheritance is related to a mutation in an autosome, i.e. any chromosome that is not a sex chromosome. Dominant inheritance pattern implies that it is enough with only one mutant allele for the disease to be expressed. This means that

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**5. Familial dilated cardiomyopathy**

**5.1 Inheritance patterns**

called a *de novo* mutation.

*5.1.1 Autosomal dominant*

Autosomal recessive inheritance is caused by mutation in a gene situated on an autosome but requires both the copy inherited from the father and the copy from the mother to be mutaded. For the mutation to cause the disease to be expressed the carrier needs to be homozygous for the mutation. This inheritance pattern requires both parents to carry at least one gene affected by the mutation. Men and women are equally as likely to inherit two affected gene copies from a certain pair of parents. If both parents carry one mutated gene, the offspring has a 25% risk of inheriting two mutated gene copies.
