Complications of Implantable Cardioverter Defibrillator and Their Potential Risk Factors in Patients with Hypertrophic Cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) has different complications such as cardiac arrhythmia and sudden cardiac death (SCD). Insertion of an implantable cardioverter defibrillator (ICD) is recommended for HCM patients who are at high risk of SCD and malignant arrhythmias, despite having their own potential complications. Hypothesis. We aimed to investigate the prevalence of different complications of ICD insertion and the impact of the potential influential baseline characteristics in a one-year follow-up period. Methods This was a retrospective study with a total of 71 HCM patients with ICD insertion. We evaluated the prevalence of different complications of ICD implantation and the impact of baseline characteristics on the occurrence of ICD complications using multivariate regression analysis in three 4-month periods. Results In a one-year follow-up, 13 patients (18.3%) experienced at least one of the complications including pneumothorax, lead failure, ICD infection, inappropriate shocks, perforation, and upper limb deep vein thrombosis (DVT) with no mortality. Inappropriate shocks were reported as the most common (11.3%) complication during this period, with a gradual increase in the second (4.2%) and third (5.6%) follow-up sessions. Among all of the baseline characteristics that were investigated in this study, a positive history of hypertension was the only risk factor with significant impact on the occurrence of complications (P = 0.01). Conclusion We demonstrated the occurrence of complications during a one-year follow-up as 18.3% in HCM patients with ICD insertion. A positive history of hypertension was the only baseline characteristic affecting the occurrence of complications, and inappropriate shocks were the most common complication.


Introduction
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder that afects approximately one in every 500 individuals and accounts for one percent of all of the heart disease cases.It is characterized by abnormal thickening of the walls of the ventricles, which can lead to a variety of complications including heart failure, cardiac arrhythmias, and sudden cardiac death (SCD) [1,2].
Prior studies had estimated the annual mortality rate of HCM to be between 3 and 6%; however, recent investigations have shown this rate to have decreased to less than 1% due to technological advancements, such as the insertion of an implantable cardioverter defbrillator (ICD) [3][4][5][6].
ICDs are often recommended for patients with HCM who are at high risk of SCD [7,8].However, despite their efectiveness in preventing SCD, ICDs are not free of their own potential complications, including inappropriate shock and device-related adverse events that can afect patients' quality of life and overall health outcomes [9][10][11][12].
According to the aforementioned elaborations, we aimed to investigate the prevalence of various complications resulting from ICD implantation in individuals with HCM, as well as to explore the potential risk factors that may have an impact on these complications in a retrospective cohort study.

Materials and Methods
We retrospectively analyzed data from 71 participants with HCM who underwent ICD insertion and were referred to Rohani Hospital in Babol from March 2011 to March 2021.Accordingly, they were investigated regarding the prevalence of diferent complications of ICD insertion and infuential baseline characteristics during a one-year followup period divided into three equal intervals of four months.All HCM patients aged 18 or above who were referred to our hospital were included in this study, while nonhypertrophic cardiomyopathies and the history of cardiac surgery were our exclusion criteria.An ICD device manufactured by Medtronic (Medtronic Inc., Minneapolis, MN) was inserted for all of the participants.Te diagnosis of HCM was based on the clinical presentations and echocardiography fndings [1,13,14].HCM was characterized by the presence of left ventricular hypertrophy (LVH) that cannot be explained by other potential causes like hypertension or infltrative disorders.Te hypertrophy associated with HCM is often asymmetric and typically involves the septum.A maximal wall thickness of 15 mm is commonly used as a cut-of point for diagnosis.In addition, a septal to posterior wall ratio of 1.3 or greater, as determined by imaging modalities such as echocardiography, computed tomography (CT), or cardiovascular magnetic resonance (CMR), is strongly indicative of HCM [15,16].After confrmation by imaging modalities, further history, electrocardiography (ECG), and laboratory tests were taken.In addition, baseline characteristics including age, height, weight, and clinical fndings such as ICD implantation indications and sudden cardiac arrest (SCA) risk classifcation were investigated.
Te complications associated with ICD insertion were categorized into two groups: those related to the implantation itself and those not related to the implantation.We examined complications such as hematoma, perforation, pneumothorax, deep vein thrombosis (DVT) of the upper limb, ICD lead failure, and lead infection as implantationrelated complications.In addition, we investigated inappropriate shocks as nonimplantation-related complications.Te necessary treatment measures were implemented accordingly.ICD inappropriate shocks were defned as cardiac shocks that occurred, following atrial fbrillation, sinus tachycardia, or device defect.Conversely, appropriate shocks were those that happened following ventricular fbrillation (VF) with a duration of less than 220 milliseconds or sustained VT (more than 30 beats).ICD lead failure was detected using an electrocardiogram performed during each follow-up session.Furthermore, an echocardiography was performed at each follow-up time to measure the left ventricular ejection fraction (LVEF).
Subsequently, we examined the infuence of various baseline characteristics on the occurrence of complications following ICD insertion.Tese characteristics included gender, age, history of diabetes mellitus (DM), and hypertension, as well as the use of antiarrhythmic drugs.In terms of hypertension history, we considered all patients, including those with controlled and uncontrolled hypertension, as well as those with DM.Te information regarding both hypertension and DM was obtained through selfreporting by the patients.
Sampling was taken using the convenience method with the sample size determined based on the possibility of 3.4% annualized ICD complications reported by Schinkel et al. [9], resulting in a minimum of 51 participants required for this study.Tis study was conducted by an approved ethical number of IR.MUMS.NURSE.REC.1400.083from Babol University of Medical Sciences.In addition, written informed consent was obtained from all participants involved in this study.

Statistical Analysis.
We analyzed data using the IBM SPSS Statistics for Windows, version 23 (IBM Corp, Armonk, NY, USA).Te p value <0.05 was considered statistically signifcant.We used mean and standard deviation (SD) to express the quantitative data and frequency and percentage to express the qualitative data.We analyzed data using a t-test for quantitative variables and a chi-square test or Fisher's exact test for qualitative variables.In addition, logistic regression test was performed to examine the potential risk factors that may infuence the complications of ICD insertion.

Results
A total of 71 participants with HCM were investigated in this study.Te mean ± SD (range) age of the participants was 61.3 ± 15.0 (34-93) years, of whom 41 (57.7%) and 30 (42.3%) were male and female, respectively.A total of 58 (81.7%) participants had no complications during a one-year follow-up period, while the other 13 (18.3%)participants experienced some kind of complication following ICD insertion (Figure 1).
Te baseline characteristics including age, gender, positive history of DM and hypertension, and antiarrhythmic drugs consumption were compared between the patients with and without complications.Hypertension was the only variable that showed a signifcant diference between the two groups (P = 0.03).A comparison of diferent variables between the two groups is presented in Table 1.

Cardiology Research and Practice
During the one-year follow-up period, we observed various complications related to ICD implantation, such as ICD lead failure, ICD infection, perforation, pneumothorax, and upper limb DVT.In addition, we observed inappropriate shocks as complications not directly related to ICD implantation.Te prevalence of these complications in three diferent follow-up periods is shown in Table 2.During the frst follow-up period, no complications related to ICD lead failure were reported.However, each of the other complications including pneumothorax, perforation, upper limb DVT, ICD infection, and inappropriate shock had the occurrence rate of 1.4%.In addition, the mean ± SD LVEF of patients with HCM was 52.2% ± 4.7% in this period of time.
In the second follow-up period, no complications in terms of pneumothorax, perforation, or lead infection were reported.A total of 3 (4.2%)patients experienced an inappropriate shock, and the occurrence of each upper limb DVT and lead failure was 1.4%.Te mean ± SD LVEF of participants in the second follow-up period was 51.8% ± 4.4%.
During the third follow-up, none of the patients experienced complications of pneumothorax, perforation, upper limb DVT, lead infection, or lead failure.However, 4 (5.6%)patients experienced an inappropriate shock.Te device was found to be functioning properly in 67 (94.4%) of the participants, and the mean ± SD LVEF was 51.7% ± 4.8%.
Noteworthy, no patient died during our one-year followup.Inappropriate shock was the most common complication (11.3%) during this period, which increased notably in the second and third follow-up sessions.
Logistic regression analysis (Table 3) demonstrated that hypertension was associated with an 8.5-fold increase in the risk of ICD implantation complications (P � 0.01).No signifcant infuence was found for other variables investigated in this study.

Discussion
We aimed to estimate the prevalence of diferent complications resulting from ICD insertion in HCM patients and investigate the impact of potential infuential risk factors  over a one-year follow-up period.Te prevalence of complications was estimated to be 18.3% in the total studied population during this time.Inappropriate shocks were found to be the most prevalent complication following ICD implantation with a prominent increase in the second (4.2%) and third (5.6%) 4-month follow-up sessions.Furthermore, hypertension was the only risk factor with a signifcant infuence on the occurrence of complications in this study; no signifcant impact was observed for other variables mentioned in this manuscript.HCM is a common inherited cardiac disorder afecting about one in every 500 individuals.Tis condition may lead to various adverse efects such as heart failure and SCD [1,2].Recent investigations have shown that the mortality rate of this disease has been decreased from 3-6% to less than 1% due to the use of technological advancemnts, such as ICD insertion [3][4][5][6].However, it may have some potential complications including inappropriate shock and some device-related side efects such as perforation, pneumothorax, and lead infection [9][10][11][12].In addition, these complications may be afected by a variety of risk factors such as the positive history of hypertension, DM, age, gender, and antiarrhythmic drug consumption which have been evaluated in this study.

Cardiology Research and Practice
Although few studies have investigated the prevalence of diferent complications of ICD insertion in HCM patients in other countries, this manuscript represents the frst study conducted in Iran on this matter.In a study by Lin et al. [17], 181 participants with HCM were investigated regarding the prevalence of potential complications subsequent to ICD implantation during a mean follow-up of 59 months.Accordingly, 65 (36%) patients experienced some kind of complication during follow-up time.Similarly, they reported that inappropriate shocks were the most prevalent complication of ICD insertion.Furthermore, patients with atrial fbrillation and younger age were at higher risk of inappropriate discharges.In the present study, no signifcant impact of age was observed on the occurrence of complications.In addition, atrial fbrillation was not among the variables considered in our article.
In another retrospective study conducted by Syska et al. [10], a total of 104 HCM patients who underwent ICD insertion were investigated with a mean follow-up of 4.6 years.ICD complications consisted of inappropriate discharges (33.7%), lead failure (12.5%), and lead infections (4.8%) among participants during that period.In addition, four individuals died during the total follow-up time.Similar to our results, inappropriate shocks were the most prevalent complication reported during the follow-up period.In our article, no mortalities were reported, which could be attributed to the smaller sample size and shorter follow-up time compared to that study.
In another study, Vriesendorp et al. [11] included a total of 134 participants with HCM who were treated with ICDs.Subsequently, outcomes and complications following ICD insertion were investigated; 20 (14.9%) patients of the total participants experienced some kind of device-related complication during the follow-up period.
Tey examined the impact of potential variables such as QRS duration before the procedure on the occurrence of inappropriate shocks following ICD insertion.No signifcant impact was observed between all the variables evaluated, except for the device manufacture.All ICDs implanted in our study were manufactured by Medtronic; hence, we were unable to assess the infuence of device manufacture in this article.On the other hand, a positive history of hypertension, which had a signifcant efect on the prevalence of complications in our study, was not examined in their study.
In a single-center study by Frommeyer et al. [19], 18 HCM patients who were treated with subcutaneous ICD (S-ICD) were investigated regarding device complications with a follow-up duration of at least six months.Four participants (22%) experienced at least one episode of inappropriate discharge during follow-up time.Tis was indicative of an increased risk of inappropriate shocks following ICD insertion, similar to our study.Te diference between our fndings might be due to the smaller sample size of their study compared to ours.
In a cohort study conducted by Lambiase et al. [20], a total of 99 HCM patients and 773 non-HCM patients who underwent S-ICD were investigated over a mean follow-up time of 637 days.During the follow-up, 12.5% of the 99 HCM patients experienced an inappropriate shock which was similar to the fndings in non-HCM patients (10.3%).Tese results are consistent with our fndings.
Our study had some limitations, including a small sample size and a short follow-up period.Moreover, we only included a positive history of hypertension and DM as comorbidity disorders, potentially overlooking other comorbidities such as chronic kidney disorders, ischemic heart diseases, and dyslipidemia, which were not considered in this study.Nevertheless, there were also some strength points.To the best of our knowledge, this study was the frst research carried out in our country concerning the prevalence of ICD complications and potential infuential factors in HCM patients.In addition, we assessed the prevalence of various complications subsequent to ICD insertion at three diferent follow-up sessions, making our fndings more precise and reliable compared to other studies conducted.

Conclusion
According to the fndings of the present study, the prevalence of diferent complications of ICD insertion in patients with HCM was estimated to be 18.3% in a one-year follow-up time.In addition, inappropriate shocks were reported as the most prevalent adverse event observed during this period of time.
Regarding the impact of diferent risk factors, a positive history of hypertension was the only variable that had a signifcant infuence on the prevalence of ICD complications.

Table 2 :First 4
Prevalence of diferent complications and LVEF following ICD insertion in a one-year follow-up divided into three equal parts.Variables of the data of the complications are expressed as the frequency and percentage for diferent complications of ICD insertion.LVEF is reported in the mean ± SD.DVT, deep vein thrombosis; ICD, implantable cardioverter defbrillator; LVEF, left ventricular ejection fraction.

Table 1 :
Comparison of diferent baseline characteristics between HCM patients with and without complications following the insertion of an implantable cardioverter defbrillator.
All data are expressed as the frequency and percentage for qualitative variables or the mean ± standard deviation for quantitative variables.Data analysis was performed using the chi-square test or Fisher's exact test for qualitative variables and t-test for quantitative variables.DM, diabetes mellitus; HCM, hypertrophic cardiomyopathy.Figure 1: Prevalence of complications following ICD insertion in patients with hypertrophic cardiomyopathy in a one-year follow-up period.

Table 3 :
Multivariate analysis of the impact of diferent baseline characteristics on complication occurrence following ICD insertion.