The mortality benefit of implantable cardioverter defibrillator (ICD) therapy in patients with hypertrophic cardiomyopathy (HCM) who have survived or are at increased risk for sudden cardiac arrest (SCA) is well established. However, risk stratification of these patients is imprecise and based on clinical risk factors for SCA which have a low positive predictive value.1^–3 Recent publication of data from an international, multicentre registry suggests that the presence of a single risk factor may be sufficient to warrant ICD implantation,4 5 which is likely to substantially increase the number of HCM patients undergoing prophylactic ICD implantation.

However, ICD therapy is not without risk, and may result in potential device-related complications including inappropriate ICD shocks. Due to young age at implant and increased prevalence of atrial fibrillation as compared with the general population,6 patients with HCM may be at an especially higher risk of inappropriate shocks. Whether this is the case is not well known, as the precise risk of inappropriate ICD therapies in this patient population is not well described. To determine this, we reviewed our experience with ICD therapy in HCM patients at the Mayo Clinic.

METHODS

Patient selection and clinical characteristics

All patients were evaluated in the HCM clinic at Mayo Clinic. The diagnosis of HCM was based on the presence of characteristic clinical, echocardiographic and electrocardiographic features, and ventricular hypertrophy in the absence of other clinical causes.7^–9 All patients with HCM who underwent ICD implantation between January 1988 and December 2005 were included. Clinical demographics and data including ICD implant indication and SCA risk stratification were obtained from the electronic medical record, where data are prospectively entered. Primary prevention risk factors were a family history of SCA in a first-degree relative, septal hypertrophy (⩾30 mm), non-sustained ventricular tachycardia and unexplained syncope.1^–3 Death notification was obtained from the medical record or from the US Social Security Death Index database.

ICD implantation procedure and complications

ICDs implanted prior to 1994 required a thoracotomy approach and utilised epicardial defibrillator patch electrodes and epicardial screw in pacing and sensing leads. All subsequent ICDs were implanted via a non-thoracotomy approach with a transvenous lead for pacing sensing and high-output shock placed in the right ventricle. In patients who had sinus node dysfunction or atrioventricular block, and were not in atrial fibrillation, an atrial lead was also implanted. In several cases, a right atrial lead was implanted to improve arrhythmia discrimination. Defibrillation threshold testing (DFT) was performed at the time of initial ICD implantation in most patients. In most cases, two inductions of VF were performed with the first shock being programmed at either 14 J or 21 J. If 14 J was unsuccessful at restoring sinus rhythm, a second shock at 21 J was then delivered. In most cases a “step down to failure” method was not used. DFT was considered high if ⩾15 J.

Clinically significant pocket haematoma, cardiac perforation requiring pericardiocentesis, pneumothorax, upper-extremity deep-venous thrombosis, ICD lead failure (acute within 24 h or chronic >24 h) requiring lead revision or replacement, and device infection requiring lead and generator explantation were considered implant-related complications. Complications (other than lead revisions) were classified as early if occurring ⩽1 month following ICD implantation or late if >1 month following implantation.

ICD follow-up and classification of shock therapies

All ICDs were programmed at implant to include a ventricular fibrillation (cycle length <220 ms) therapy zone with a single burst of antitachycardia pacing prior to shock therapy or during charging, depending on device manufacturer and model implanted. Therapies for ventricular tachycardia or more than a single burst of antitachycardia pacing were not generally used. Data derived from ICD interrogation from the date of implant until December 2007 were included for analysis. All devices were interrogated the day following implantation to determine appropriate device function. Subsequent device interrogations were routinely performed at 1 month and every 3 months thereafter, and at the time of any clinical visits. Any patient who did not return for routine device interrogation was contacted by the primary investigators using a detailed questionnaire to determine occurrence and frequency of ICD shocks and, where appropriate, ICD electrograms reviewed.

After review of all ICD electrograms, ICD shocks were classified as appropriate if triggered by ventricular fibrillation (cycle length <220 ms) or sustained ventricular tachycardia (>30 beats) falling within appropriate ICD therapy zone, and inappropriate if triggered by sinus tachycardia, atrial arrhythmias or device malfunction.

Statistical analysis

The yearly risk of device complications was determined using Kaplan–Meier estimates. Rates of appropriate and inappropriate therapies were determined per 100 patient-years and also by Kaplan–Meier estimates. Differences in rates of appropriate and inappropriate ICD therapies were determined by the logrank statistic. A Student t test and χ² test or Fisher exact test were used to determine differences in characteristics of patients with and without ICD therapies. A receiver operating characteristic (ROC) analysis was used to determine the predictive value of the same clinical characteristics (age, ejection fraction, septal thickness, left ventricular outflow tract gradient, DFT at implant). Relative risk of inappropriate ICD therapies was assessed using univariate and multivariate analysis performed with a Cox regression model, which included multiple demographic and clinical characteristics. Survival following ICD implantation was determined by Kaplan–Meier estimates. Patients were followed from the time of ICD implantation to an end point of death from all causes. A p value of <0.05 was considered statistically significant.

All data collection and statistical analysis were performed by the primary investigators (GL and PAB).

This study was approved by and conducted in accordance with guidelines established by the Mayo Clinic Institutional Review Board.

RESULTS

Patients and baseline characteristics

Between January 1988 and December 2005, 2007 patients were evaluated in the HCM clinic, of which a total of 342 patients received ICD for SCA prophylaxis. Of these, 204 patients underwent ICD implantation at Mayo Clinic after clinical risk assessment, and were included. Of these, 23 patients could not be contacted despite telephone and written requests for information, and were considered lost to follow-up. Baseline characteristics and demographics of the 181 patients who therefore comprised the study population are summarised (table 1). At the time of device implantation, mean age of patients was 44 (SD 17) years (median 45 years, range 5 to 83 years; 112 males, 62%), with mean ejection fraction of 68% (10%). There were 49 (27%) patients <35 years old, and of these 21 (12%) were <18 years old. Average septal thickness was 20.49 (6.66) mm (range 9 to 46 mm, median 20 mm). In 23 patients (14%) the septal thickness was ⩾30 mm. Left ventricular outflow tract gradient was considered to be moderate or severe (⩾36 mm Hg) in 36 patients (21%) with average left ventricular outflow tract gradient of 25.56 (33.47) mm Hg (range; no gradient to 213 mm Hg, median 12 mm Hg).

Atrial fibrillation was present in 79 patients (44%) but was permanent in only nine patients. Surgical septal myectomy was performed prior to ICD implantation in 72 patients and alcohol septal ablation in 10 (table 1).

A majority of patients were receiving either beta blockers or calcium-channel blockers. Use of antiarrhythmic drugs was limited in our study group, and was almost exclusively disopyramide or amiodarone (table 1).

ICD indication and implantation

Indication for ICD implant was for primary prevention in 155 patients (86%), and for secondary prevention due to documented sustained ventricular tachycardia or SCA episode in 26 patients (15%). In the group who were implanted for primary prevention, 71 (46%) had ⩾2 SCA risk factors. A family history of SCA in a first-degree relative was present in 87 (56%) patients and was the sole risk factor in 36 (23%) patients. The number of patients implanted because of a history of syncope, non-sustained ventricular tachycardia, and septal hypertrophy are shown (table 1). A hypotensive response to exercise occurred in one patient who did not have any other risk factors for sudden death in hypertrophic cardiomyopathy. Four patients had no currently accepted risk factors for sudden cardiac arrest in hypertrophic cardiomyopathy but underwent ICD implantation primarily because of the need for device implantation for the purpose of atrial defibrillation therapies (two patients), and because of symptomatic bradycardia and the need for pacing therapy (two patients) with a decision to implant ICD after clinical discussion of risk.

A dual chamber ICD was placed in 108 (60%) patients, of whom 34 had a prior history of atrial fibrillation. Symptomatic bradycardia was present in 29 patients and was due to sinus node dysfunction in 12 and atrioventricular block in 17. The mean DFT at implant was 14 (5) J. Elevated DFTs (>15 J) were present in 44 patients (26%). Defibrillation threshold testing was not performed in seven patients due to intracardiac thrombus (2), recent stroke (1), severe pulmonary hypertension (1), amiodarone loading (1), haemodynamic instability (1) and inability to induce sustained ventricular arrhythmia (1).

ICD-related complications

During a follow-up of 59 (42) months (4.92 years; 830.75 patient-years), 65 patients (36%) had a total of 88 device complications, including 42 (23%) patients with inappropriate shocks (table 2). The likelihood of any device complication (including inappropriate shocks) was 10.6 per 100 patient-years, with 81% of patients free of ICD complications at 1 year following ICD implantation. The rate of complications was highest in the first year (19%), with an average subsequent rate of 5% per year over the next 3 years (fig 1).

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Figure 1

Implantable cardioverter defibrillator (ICD) complications in hypertrophic cardiomyopathy. Kaplan–Meier estimate of rate of ICD-related complications, including inappropriate shocks (percentage free of any complications).

Device-implant-related complications included pocket haematoma in four patients (three with initial implant and one with generator change), of which one required surgical evacuation, cardiac perforation requiring pericardiocentesis in three, acute upper extremity deep venous thrombosis in one and pneumothorax in one (table 2). Lead revision was required in 24 patients, of which six were acute, and 18 were chronic, and of these, two patients with epicardial defibrillator patches required multiple lead revisions over the study period including eventual placement of transvenous leads. A device infection requiring device and lead removal occurred in eight patients (early in one and late in seven). A second procedure to revise the ICD was required in five patients due to persistently high defibrillation threshold (DFT >21 J); in one patient, the superior vena cava coil was capped to exclude it from the shocking circuit, in four patients, including one paediatric patient (6 years old), a subcutaneous array was implanted, and one additional patient had a high-output device placed, which resulted in acceptable DFT (10 J safety margin) in all patients.

Inappropriate ICD therapies

During follow-up, 29 patients (16%) had appropriate ICD therapies, and 42 patients (23%) had inappropriate ICD therapies. The likelihood of appropriate compared with inappropriate ICD discharges per 100 patient-years was 3.5 versus 5.1. During the first year following the ICD implant, the rate of inappropriate ICD therapies was higher than the rate of appropriate ICD therapies (10% vs 6%), although subsequent rates of inappropriate and appropriate ICD shocks were similar (3% vs 3%, p = 0.09, fig 2). The average rate of inappropriate ICD discharges per year was 5.3% (vs 4% appropriate ICD discharges), with a cumulative risk of 20% at 4 years.

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Figure 2

Appropriate and inappropriate implantable cardioverter defibrillator (ICD) shocks in hypertrophic cardiomyopathy. Kaplan–Meier estimates of rates of appropriate versus inappropriate ICD shocks.

Reasons for inappropriate ICD therapies were atrial fibrillation in 20 patients, sinus tachycardia in 16 and device malfunction in six. Device malfunction leading to inappropriate shock was due to T wave oversensing in four patients, noise sensed on the ventricular lead in one patient and exposure to an external electromagnetic field in one patient.

Of the 42 patients who received inappropriate shocks, seven received inappropriate shocks on multiple (>2) occasions (range 2–6 events), due to atrial fibrillation in five, sinus tachycardia in one and device malfunction (oversensing) in one. In contrast, 22 patients received multiple (>2) shocks for a single event, of which 10 had an electrical storm (⩾5 shocks) with inappropriate shocks. Multiple shocks during a single event occurred due to atrial fibrillation in 13, sinus tachycardia in eight and T wave oversensing in one.

Risk factors for inappropriate ICD therapies

Inappropriate ICD discharges occurred more often in young patients and those with a history of atrial fibrillation (table 3). Of the 42 patients who received inappropriate shocks, 21 (50%) were <35 years old. The rates of inappropriate shocks classified by age groups are shown in fig 3. Younger age at implant was predictive of future inappropriate ICD discharges by ROC analysis (AUC = 0.64, p<0.01).

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Figure 3

Device complications and inappropriate implantable cardioverter defibrillator (ICD) shocks by age group. The proportion of patients with inappropriate ICD shocks (grey bars) and device complications (black bars) in each age group are shown.

Gender, ejection fraction, septal thickness, left ventricular outflow tract gradient, DFT at implant and ICD implant indication (primary versus secondary) were similar in patients with and without inappropriate ICD therapies (p>0.05 for all, table 3) and were not predictive of increased risk of inappropriate shocks by ROC analysis (AUC <0.60, p>0.05 for all). Use of beta blockers and use of an atrial lead were also similar among patients with and without inappropriate ICD therapies (table 3).

The frequency of inappropriate ICD discharges was similar in patients with few or multiple risk factors for sudden cardiac arrest (table 3). No specific risk factor (family history, occurrence of non-sustained ventricular tachycardia, syncope or massive septal hypertrophy) was associated with increased inappropriate ICD discharges (p>0.05 for all). Neither surgical myectomy nor alcohol septal ablation was associated with increased inappropriate ICD shocks.

Only age <35 years at the time of ICD implantation (HR 3.37, CI 1.80 to 6.32, p<0.01) and atrial fibrillation (HR 2.48, CI 1.32 to 4.74, p<0.01) were significant predictors of increased risk of inappropriate ICD discharges in both univariate and multivariate analysis (table 4). The use of beta blockers or dual-chamber ICD, surgical septal myectomy and alcohol septal ablation was not associated with a decreased risk of inappropriate ICD discharges (table 4, part A).

Survival

During the follow-up period, there were 20 deaths, due to heart failure (three), postoperative complications following coronary artery bypass grafting (one), postoperative complications following left ventricular assist device implantation (one), postoperative complications following surgical myectomy (one), postoperative complications following non-cardiac surgery (one), motor vehicle accident (one), pneumonia (one), ovarian carcinoma (one), myocardial infarction (one), perforated colon (one), renal failure (one), subdural haematoma (one), and unknown causes (six). Four patients underwent cardiac transplant due to worsening haemodynamics and heart failure. Survival at 1 year was 97% (fig 4).

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Figure 4

Survival following implantable cardioverter defibrillator (ICD) implantation. Kaplan–Meier estimate of survival (free of death from all causes) following ICD implantation.

DISCUSSION

The major finding of this study is that the incidence of device complications in HCM patients is not insignificant, occurring in 36% of patients during follow-up, with the highest rate (19%) of device complications in the first year following ICD implantation. Inappropriate ICD shocks were the most common complication occurring in 42 (23%) patients. The rate of inappropriate ICD shocks is also highest in the first year following implantation (10%), with an average rate of 5.3% per year. Younger age (<35 years) and a history of atrial fibrillation are associated with a higher risk of inappropriate ICD shocks. Use of beta blockers, addition of an atrial lead, or surgical septal myectomy was not associated with decreased risk of inappropriate ICD therapies.

Although the high risk of ICD complications, especially in the first year following ICD implantation (19%), is in part attributable to implant-related complications, such as haematoma or cardiac perforation, the incidence of these complications (2% for each) is similar to that for permanent pacemakers and other implantable cardiac devices in the general population.10 11 Incidences of other early complications, including the need for acute lead revision (3.3%) or early device infection (<1%), are also low and similar to previously reported rates.4 10^–12 Thus, the major complication of ICD therapy in our study population was inappropriate ICD discharges.

The incidence of inappropriate ICD shocks observed in our study is similar to other high risk HCM cohorts, including a recent multicentre registry which reported a 27% incidence of inappropriate ICD shocks,4 12 13 and to other young, high-risk populations—for example patients with Brugada syndrome (20–36% incidence of inappropriate shocks).14 15 Our observation that the rate of inappropriate ICD shocks during the first year following ICD implantation was higher than the rate of appropriate ICD shocks (10% vs 6%) is important and also consistent with the rates found in other high-risk HCM and Brugada cohorts.12 14 This emphasises that the risk of inappropriate ICD shocks in this young and largely primary prevention patient population is not insignificant. Both younger age at implant and atrial fibrillation were associated with increased risk of inappropriate ICD shocks. Although the mechanism by which age impacts risk of inappropriate shocks is not clear from this study, one reason may be due to increased likelihood of sinus tachycardia in young, active patients falling within a ventricular treatment zone.

Prior studies have suggested that addition of an atrial lead might aid in discrimination of supra versus ventricular arrhythmias and would therefore decrease the frequency of inappropriate shocks, yet data have been conflicting.16 17 Our findings do not support the use of an additional atrial lead for prevention of inappropriate shocks in patients with HCM or the efficacy of beta blockers to facilitate rate control of atrial fibrillation. This suggests that methods to prevent inappropriate shocks of patients in atrial fibrillation may not be as beneficial, and that perhaps therapy targeted towards abolishing atrial fibrillation, such as pulmonary vein isolation procedures or antiarrhythmic drug therapy, may be more effective.18

Surgical septal myectomy, which may be associated with a decreased risk of appropriate ICD shocks,19 may also abolish atrial fibrillation in up to 46% of patients with preoperative atrial fibrillation.20 However, our findings do not suggest that surgical septal myectomy protects against risk of inappropriate ICD shocks.

Although the mortality benefit of ICD implantation in high-risk HCM patients is proven, our study reinforces the notion that ICD therapy, although potentially life-saving, is not benign.21 22 Since current methods of risk stratification are imperfect, the decision to implant an ICD in a young patient with HCM should be undertaken with caution and careful discussion of potential complications. Newer techniques that may allow more direct assessment of myocardial vulnerability to ventricular arrhythmias hold promise and may be useful in the decision to implant an ICD.23 However, this should be carefully weighted against the risk of device-related complications, particularly in younger individuals and patients with atrial fibrillation.

LIMITATIONS

One limitation of our study is its retrospective design. However, it represents a single centre experience in a large number of patients with fairly uniform implant techniques, device programming and follow-up. Second, although follow-up was uniform, it was in most cases limited to clinically indicated evaluations. Third, 23 patients were lost to follow-up, and so outcomes in these patients are unknown. However, this would likely lead to an underestimation rather than overestimation of device complications.