The impact of implantable cardioverter defibrillator on the prognosis of nonischemic dilated cardiomyopathy patients compared with standard medical treatments

Abstract Background Patients with nonischemic dilated cardiomyopathy (DCM) are susceptible to arrhythmias and implantable cardioverter defibrillator (ICD) in addition to medical treatments may help prevent sudden cardiac death (SCD) and improve survival in this population. Hypothesis We aim to investigate the impact of ICD insertion on survival and prognosis of patients with nonischemic DCM. Methods We retrospectively analyzed data from patients with nonischemic DCM treated with medical therapy with or without ICD who referred to our hospital from January 2020 to November 2021. Patients were divided based on the treatment that they had received into two equal groups. Different variables including demographic features, comorbidities, medical treatments, hospitalization rate, function class, and left ventricular ejection fraction before and after treatments were investigated in this study. In addition, variables in survival including overall survival (OS) and SCD were compared between the two groups. Results A total of 120 patients were investigated in this study. Mean ± SD of age and follow‐up time of patients were 64.0 ± 12.7 years old and 61.2 ± 15.9 months, respectively. Ten (16.7%) patients with medical therapy, and seven (11.7%) patients with ICD and medical therapy died during the follow‐up period (p = 0.25). However, the two groups had a significant difference regarding SCD (11.7% vs. 1.7%, p = 0.02). Conclusion In patients with nonischemic DCM who had undergone ICD insertion in addition to standard medical treatments, SCD was significantly reduced compared with patients receiving just medical treatments. OS had no significant difference between our two studied groups.


| INTRODUCTION
Dilated cardiomyopathy (DCM) is considered as one of the common causes of heart failure with general prevalence of one case per 250 individuals. 1 In addition, with annual mortality rate of 25%-30% and 5-year mortality rate of 50%, it is recognized among the most important causes of fatality and a burden on global health system. 2 Patients with DCM are prone to arrhythmias leading to sudden cardiac death (SCD) in about 30% of cases. 3 Medical treatments such as beta-blockers are recognized as influential and potential agents which can increase survival and cardiac function of patients with DCM. 4,5 Moreover, they might prevent SCD by reducing the possibility of arrhythmias. 6 However, according to current guidelines, using implantable cardioverter defibrillators (ICDs) in addition to medical treatments is recommended for selected DCM patients to prevent sudden cardiac arrhythmias. 7 Mortality advantages of ICD insertion are mostly recognized in patients with ischemic DCM.
However, its benefits in nonischemic DCM have remained controversial. 8 Despite coronary heart disease being generally considered as the main cause of SCD, up to 20% of cases of SCD is due to nonischemic cardiomyopathies that lead to cardiac arrhythmias. 9 Although few articles have been published regarding survival outcomes of ICD insertion in patients with nonischemic DCM recently, their findings regarding overall survival (OS) and SCD were conflicting. [10][11][12] In this study, we aim to investigate whether ICD insertion was effective for increasing OS and prognosis of patients with nonischemic DCM who underwent medical treatments in a retrospective cohort study.

| MATERIALS AND METHODS
We retrospectively analyzed data from 120 patients with nonischemic DCM treated with medical therapies with or without ICD insertion who referred to Masih Daneshvari Hospital from January 2020 to November 2021.
All patients with all of the following criteria are included in this study: 1. Nonischemic DCM patients with the age between 21 and 85 years old, who were on the full tolerable guideline-directed medical treatment 2. Left ventricular ejection fraction (LVEF) ≤ 35% as confirmed by transthoracic echocardiography (Vivid 6 echo machine, using twodimensional and Simpson methods).
3. Symptoms of heart failure and New York Heart Association (NYHA) functional class (FC) of II to IV.

Evidence of DCM confirmed by echocardiography.
On the other hand, all of the patients with a history of coronary artery disease, congenital heart failure, and acute myocarditis, confirmed by coronary angiography or stress imaging study were excluded from our article.
Patients were divided into two groups based on the kind of therapies they had received. The first group consisted of the patients that were candidates for ICD and cardiac synchronization therapy (CRT) but declined the procedure for nonmedical reasons and received only medical treatment.
The second group were ICD candidates whom device was implanted for.
Both groups had received the following treatments: angiotensinconverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta-blockers (such as carvedilol and metoprolol), diuretics (such as thiazide and furosemide), aldosterone antagonists, and digoxin in those patients who did not have contraindication. All patients had received medical treatment or ICD insertion for at least 1 year before the study.
The sample size was determined based on the 5-year lifespan of 50% for nonischemic DCM patients receiving medical treatment and 75% for nonischemic DCM patients receiving ICD and CRT, resulting in 60 patients for each group.
Complications such as pneumothorax, hemothorax, cardiac tamponade, and mild bleeding during ICD implantation were rarely observed which necessary treatment measures were taken. Other complications such as thrombosis, infection, and displacement of the leads were also observed and were adequately treated. No deaths related to ICD insertion were reported.
Patients were followed up every 3 months for evaluation of heart failure progression, vital signs, mortality, sudden death rate, and arrhythmias for at least 1 year. Different variables including demographic features, underlying diseases, medical treatments, hospitalization rate, and NYHA FC and LVEF before and after treatments were evaluated in this study. In addition, variables in survival including OS and SCD were compared between the two groups.
SCD was defined as mortalities that were reported due to cardiac arrhythmia and OS was considered as mortalities happened due to all causes including cerebral emboli, severe heart failure, and pulmonary edema.  Table 1. Most of our patients had NYHA FC III in both groups. Patients' FC and LVEF before initiating treatment were not significantly different between the two groups. Also, no significant difference regarding underlying diseases was observed between the two studied groups at the beginning of the diagnosis (Table 1). While one of the 7 (1.7%) deaths among ICD group was due to SCD, 7 of 10 (11.7%) deaths from the medical therapy group was due to SCD during the follow-up period (p = 0.02).

| Statistical analysis
In Figures 1 and 2 We also had some limitations in this study; The most important one is the limited number of patients who had undergone ICD insertion. Also, this is a retrospective study which has the limitations related to the study design. Some of our patients were candidates for ICD at the time of diagnosis but they were unwilling to receive ICD; as a result, they had only received medical treatments. None of the nonischemic DCM patients in our study was receiving amiodarone F I G U R E 2 Comparison of overall survival between ICD group and medical therapy group. ICD, implantable cardioverter defibrillator and we could not compare this drug with ICD, which is controversial topic in DCM patients. Therefore, further trial studies are warranted to validate our results. Taken all this together, risk stratification is required to determine the nonischemic DCM patients that may benefit from ICD implantation.

| CONCLUSION
Our study revealed that ICD implantation significantly reduced cardiac arrhythmia leading to SCD in patients with nonischemic DCM who were receiving standard medical treatments. ICD insertion had no significant benefit in other investigated clinical variables including OS, hospitalization rate, and cardiac function implied by LVEF and NYHA FC.

ACKNOWLEDGMENTS
The authors thank all the volunteers who participated in the study.