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Relation of Advanced Heart Failure Symptoms to Risk of Inappropriate Defibrillator Shocks
Relation of Advanced Heart Failure Symptoms to Risk of Inappropriate Defibrillator Shocks Haitham Hreybe, MD, Rana Ezzeddine, DrPH, William Barrington, MD, Raveen Bazaz, MD, Sandeep Jain, MD, Ogundu Ngwu, MD, and Samir Saba, MD* Inappropriate implantable cardioverter-defibrillator (ICD) shocks continue to be a major source of distress to patients and a drain on the health care system. Expanding indications for ICD implantation include a large portion of patients with heart failure. This study investigated the relation between inappropriate ICD shocks and the severity of heart failure symptoms. Predictors of the time to first inappropriate ICD therapy were investigated in 230 consecutive patients implanted in 2001 and 2002. Thirty-two patients received 42 inappropriate shocks during a median follow-up of 501 days. Inappropriate shocks were due to atrial fibrillation (AF) or tachycardia (n ⴝ 31), other supraventricular tachycardias (n ⴝ 6), sinus tachycardia (n ⴝ 3), and noise or double counting (n ⴝ 2). The time to first inappropriate ICD shock was earliest in patients with advanced classes of heart failure (1- and 2-year shock-free survival of 79% and 70% for patients in New York Heart Association [NYHA] class III or IV vs 92% and 88% for patients in NYHA class I or II, respectively, p ⴝ 0.02). After correcting for age, gender, the presence of coronary artery disease, the presence of AF, the use of  blockers, and indication for ICD implantation in a Cox regression model, advanced heart failure (NYHA class III or IV) remained an independent predictor of first inappropriate ICD shocks (hazard ratio 2.7, p ⴝ 0.01). Other predictors of the time to first inappropriate ICD shock included the presence of AF as the baseline rhythm at the time of the ICD implantation and the absence of coronary disease. In conclusion, inappropriate ICD shocks are predominantly due to AF. Advanced heart failure is an independent predictor of the time to first inappropriate ICD shocks. The effect of ICD programming and antiarrhythmic drug therapy on the incidence of inappropriate shocks deserves further investigation. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;97:544 –546) Inappropriate implantable cardioverter-defibrillator (ICD) shocks1– 4 continue to be a major source of distress to patients and a drain on the health care system.5 Expanding indications for ICD implantation include a large portion of patients with heart failure.6 –10 In this study, we investigated the impact of the severity of heart failure, as measured by the New York Heart Association (NYHA) class, on the incidence of inappropriate ICD shocks. •••
All patients who underwent ICD implantations at the University of Pittsburgh Medical Center from July 2001 to December 2002 were included in the study. Patients’ electronic medical records and cardiac electrophysiology clinic records were analyzed for baseline demographics, electrocardiographic data, clinical characteristics, including NYHA class of heart failure, the left ventricular ejection fraction, underlying heart disease, indication for ICD implantation, medications, and associated medical conditions. University of Pittsburgh, Pittsburgh, Pennsylvania. Manuscript received May 1, 2005; revised manuscript received and accepted August 29, 2005. * Corresponding author: Tel: 412-647-6272; fax: 412-647-7979. E-mail address: [email protected] (S. Saba). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.08.074
Data from the ICDs were also collected and reviewed, with a focus on device programming, the frequency and timing of therapy, and cardiac rhythm leading to the ICD shock. Patients with previously implanted pacemakers or ICDs who underwent changes or upgrades of their devices were excluded from the study. The primary analysis of this study was to determine the effect of the severity of heart failure on the time to first inappropriate ICD shock, defined as the first shock delivered to treat nonventricular tachyarrhythmias. Most inappropriate shocks are due to rapidly conducted supraventricular rhythms, which are misclassified as ventricular tachycardia after satisfying rate and duration criteria. Continuous variables are summarized as mean ⫾ SD. Categorical variables are reported as percentages. Eventfree survival was analyzed using Kaplan-Meier productlimit methods. Adjustments for other covariates were done using the Cox proportional-hazards model. Log-rank statistics were used to test for the differences in event-free survival among the various NYHA classification groups. A p value ⱕ0.05 was considered statistically significant. Two hundred thirty patients received new ICDs at the University of Pittsburgh from July 2001 to December 2002 and were followed up for a median duration of 501 days. www.AJConline.org
Heart Failure/Inappropriate ICD Shocks in Heart Failure
545
Table 1 General characteristics of patients who received inappropriate defibrillator shocks versus those who did not Variable
Age (yrs) Men White race Coronary artery disease AF QRS (ms) Ejection fraction (%) NYHA heart failure class III or IV Primary indication for defibrillator Single-chamber defibrillator Beta-blockers Class III antiarrhythmic drugs (amiodarone [n ⫽ 45] and sotalol [n ⫽ 4])
Patients With Inappropriate Shocks (n ⫽ 32)
Patients Without Inappropriate Shocks (n ⫽ 198)
62 ⫾ 14 72% 75% 62% 28% 120 ⫾ 28 26 ⫾ 13 63%* 75% 16% 78% 16%
63 ⫾ 14 80% 77% 77% 15% 123 ⫾ 35 28 ⫾ 13 42% 78% 16% 69% 23%
* p ⬍0.05.
Thirty-two patients received inappropriate ICD shocks during the follow-up period. Table 1 lists the baseline characteristics of those patients who received inappropriate ICD therapy compared with those who did not. There were no differences between the 2 groups in any of the baseline clinical characteristics except for NYHA classification of heart failure. Patients who received inappropriate shocks were more likely to have advanced symptoms of heart failure (NYHA class III or IV) than those who did not receive spurious shocks (63% vs 42%, p ⫽ 0.026). Also, compared with patients with no shocks, patients who received inappropriate ICD shocks were more likely to have atrial fibrillation (AF) on their baseline surface electrocardiograms (28% vs 15%, p ⫽ 0.07) and less likely to have a history of coronary disease (63% vs 77%, p ⫽ 0.07). A total of 42 inappropriate shocks were delivered in 32 patients during the same median follow-up of 501 days. Of these 32 patients, 7 received 2 and 1 received 3 inappropriate shocks. These spurious ICD shocks were due to AF or tachycardia (n ⫽ 31), other supraventricular tachycardias (n ⫽ 6), sinus tachycardia (n ⫽ 3), and noise or double counting (n ⫽ 2). The type of device implanted (single chamber [n ⫽ 37], dual chamber with [n ⫽ 29] or without [n ⫽ 164] biventricular pacing) did not affect the incidence of inappropriate shocks. Of note, only 8% of patients had their rhythm discrimination algorithms (onset and stability) programmed on, at the discretion of the implanting physicians. The mean rate cutoff for ICD therapy was marginally less in patients receiving inappropriate shocks (166 vs 174 beats/min, p ⫽ 0.079), but this did not reach statistical significance. Time to first inappropriate shock was defined as the time from ICD implantation to the first day of inappropriate shock. The severity of symptoms of heart failure was a strong predictor of the time to first inappropriate ICD shock. The 1- and 2-year Kaplan-Meier estimates of the incidence
Figure 1. Kaplan-Meier curves showing time to first inappropriate ICD shock in patients with heart failure in NYHA class I or II compared with NYHA class III or IV.
Figure 2. Bar graph comparing the incidence of inappropriate ICD shocks between patients with AF and those without AF on the baseline surface electrocardiogram obtained before device implantation. The p value is adjusted for the presence of other covariates in a Cox proportional-hazards multivariate model.
of first inappropriate ICD shock were 8% and 12%, respectively, for patients in NYHA class I or II compared with 21% and 30%, respectively, in those in NYHA class III or IV (p ⫽ 0.02). The mean time to first inappropriate ICD shock was 990 ⫾ 32 days in patients in NYHA class I or II compared with 924 ⫾ 56 days in those in NYHA class III or IV (p ⫽ 0.02). Kaplan-Meier estimates of the probability curves were constructed for this comparison and are shown in Figure 1. The effect of heart failure severity on the time to first inappropriate ICD shock was also analyzed in a Cox proportional-hazards regression model. After correcting for age, gender, indication for ICD implantation, width of QRS interval, the presence of AF, the absence of coronary disease, and the use of  blockers, NYHA classification was found to be an independent predictor of the time to first inappropriate ICD shock (hazard ratio 2.7 for NYHA classes III and IV compared with classes I and II, p ⫽ 0.01).
546
The American Journal of Cardiology (www.AJConline.org)
Table 2 Multivariate analysis of the predictors of time to first inappropriate defibrillator shock Variable NYHA class III/IV versus I/II Age per 1-yr increase Gender (female vs male) ICD indication (secondary vs primary) QRS (per 1-ms increase in width) Absence of coronary artery disease Presence of AF Treatment with  blockers
Hazard Ratio
95% Confidence Interval
p Value
2.768
1.277–6.001
0.010
1.010 0.766 1.236
0.984–1.037 0.337–1.741 0.540–2.831
0.460 0.524 0.616
0.992
0.981–1.002
0.123
2.612
1.178–5.792
0.018
2.448 2.054
1.059–5.659 0.852–4.954
0.036 0.109
In addition, the presence of AF at the time of ICD implantation (Figure 2) and the absence of coronary disease were found to be significant independent predictors of the time to the first inappropriate ICD shock (hazard ratio 2.4, p ⫽ 0.04 for AF, and hazard ratio 2.6, p ⫽ 0.02 for the absence of coronary disease). Table 2 lists the results of the Cox regression analysis. •••
Our data demonstrate that patients with severe symptoms of heart failure as reflected by their NYHA classifications are more likely to receive inappropriate ICD shocks within a mean follow-up of about 16 months from the date of initial device implantation. This association between the severity of heart failure and the time to first spurious ICD shock was independent of other potential covariates, such as the age or gender of the patient, the indication for ICD implantation, electrocardiographic parameters, such as the width of the QRS complex or the presence of AF, the presence of coronary disease, or pharmacologic treatment with  blockers. This finding might have significant clinical implications for patients with advanced heart failure and their managing physicians, such as the early consideration of treatment with antiarrhythmic medications before or soon after device implantation. The recently presented but yet unpublished results of the Optical Pharmacological Therapy in Implantable Cardioverter Defibrillator Patients trial suggest a possible role for the prophylactic use of amiodarone in patients with ICDs. Also, given that patients with inappropriate ICD shocks were more likely to have AF as their baseline rhythm, consideration should also be given to early atrioventricular nodal ablation, especially in the subset of patients with rapid ventricular response rates despite pharmacologic treatment or those intolerant to drugs. Our finding of the increased frequency of inappropriate ICD shocks in patients with severe heart failure is in keeping with other reports, although scarce. Nanthakumar et al11 demonstrated a similar relation between the severity of heart failure and the incidence of inappropriate shocks in a pop-
ulation of patients with single-chamber devices only. The investigators concluded that an upgrade to a dual-chamber ICD with better rhythm discrimination algorithms could potentially reduce the number of inappropriate shocks. Our study population, in contrast, included patients with singleand dual-chamber ICDs, with no documented differences between these 2 groups in the likelihood of receiving an inappropriate ICD shock. Given that only 8.3% of the patients in our study had devices with rhythm discrimination algorithms turned on, it is very hard to draw any definitive conclusions as to the benefit s of these algorithms in a heart failure population. The effect of dual- versus single-chamber devices as well as the programming of the ICD parameters as it pertains to the therapy rate cutoffs, the detection times, and the rhythm discrimination algorithms deserves further investigation. Advanced symptoms of heart failure predict an increased risk for inappropriate ICD shocks. Larger studies are needed to confirm this relation and to identify the means of preventing inappropriate ICD shocks in patients with heart failure. 1. Nunain SO, Roelke M, Trouton T, Osswald S, Kim YH, Sosa-Suarez G, Brooks DR, McGovern B, Guy M, Torchiana DF, et al. Limitations and late complications of third generation automatic cardioverter defibrillators. Circulation 1995;91:2204 –2213. 2. Wood MA, Stambler BS, Damiano RJ, Greenway P, Ellenbogen KA. Lessons learned from data logging in a multicenter clinical trial using a late generation implantable cardioverter defibrillator. The Guardian ATP 4210 Multicentre Investigators Group. J Am Coll Cardiol 1994;24:1692– 1699. 3. Grimm W, Flores BF, Marchilinski FE. Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable defibrillators. Pacing Clin Electrophysiol 1992;15:1667–1673. 4. Rosenqvist M, Beyer T, Block M, den Dulk K, Minten J, Lindemans F. Adverse events with transvenous table cardioverter-defibrillators: a prospective multicenter study. European Jewel ICD Investigators. Circulation 1998;98:663– 670. 5. McCready MJ, Exner DV. Quality of life and psychological impact of implantable cardioverter defibrillators: focus on randomized controlled trial data. Card Electrophysiol Rev 2003;7:63–70. 6. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341:1882–1890. 7. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933–1940. 8. Connolly S, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O’Brien B. Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297–1302. 9. Moss AJ, Zareba W, Hall J, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877– 883. 10. Seidl K, Senges J. Worldwide utilization of implantable cardioverter/ defibrillators now and in the future. Card Electrophysiol Rev 2003;1:5–13. 11. Nanthakumar K, Dorian P, Paquette M, Greene M, Edwards J, Heng D, Noble J, Newman D. Is inappropriate implantable defibrillator shock therapy predictable? J Intervent Card Electrophyiol 2003;8:215–229.
All patients who underwent ICD implantations at the University of Pittsburgh Medical Center from July 2001 to December 2002 were included in the study. Patients’ electronic medical records and cardiac electrophysiology clinic records were analyzed for baseline demographics, electrocardiographic data, clinical characteristics, including NYHA class of heart failure, the left ventricular ejection fraction, underlying heart disease, indication for ICD implantation, medications, and associated medical conditions. University of Pittsburgh, Pittsburgh, Pennsylvania. Manuscript received May 1, 2005; revised manuscript received and accepted August 29, 2005. * Corresponding author: Tel: 412-647-6272; fax: 412-647-7979. E-mail address: [email protected] (S. Saba). 0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2005.08.074
Data from the ICDs were also collected and reviewed, with a focus on device programming, the frequency and timing of therapy, and cardiac rhythm leading to the ICD shock. Patients with previously implanted pacemakers or ICDs who underwent changes or upgrades of their devices were excluded from the study. The primary analysis of this study was to determine the effect of the severity of heart failure on the time to first inappropriate ICD shock, defined as the first shock delivered to treat nonventricular tachyarrhythmias. Most inappropriate shocks are due to rapidly conducted supraventricular rhythms, which are misclassified as ventricular tachycardia after satisfying rate and duration criteria. Continuous variables are summarized as mean ⫾ SD. Categorical variables are reported as percentages. Eventfree survival was analyzed using Kaplan-Meier productlimit methods. Adjustments for other covariates were done using the Cox proportional-hazards model. Log-rank statistics were used to test for the differences in event-free survival among the various NYHA classification groups. A p value ⱕ0.05 was considered statistically significant. Two hundred thirty patients received new ICDs at the University of Pittsburgh from July 2001 to December 2002 and were followed up for a median duration of 501 days. www.AJConline.org
Heart Failure/Inappropriate ICD Shocks in Heart Failure
545
Table 1 General characteristics of patients who received inappropriate defibrillator shocks versus those who did not Variable
Age (yrs) Men White race Coronary artery disease AF QRS (ms) Ejection fraction (%) NYHA heart failure class III or IV Primary indication for defibrillator Single-chamber defibrillator Beta-blockers Class III antiarrhythmic drugs (amiodarone [n ⫽ 45] and sotalol [n ⫽ 4])
Patients With Inappropriate Shocks (n ⫽ 32)
Patients Without Inappropriate Shocks (n ⫽ 198)
62 ⫾ 14 72% 75% 62% 28% 120 ⫾ 28 26 ⫾ 13 63%* 75% 16% 78% 16%
63 ⫾ 14 80% 77% 77% 15% 123 ⫾ 35 28 ⫾ 13 42% 78% 16% 69% 23%
* p ⬍0.05.
Thirty-two patients received inappropriate ICD shocks during the follow-up period. Table 1 lists the baseline characteristics of those patients who received inappropriate ICD therapy compared with those who did not. There were no differences between the 2 groups in any of the baseline clinical characteristics except for NYHA classification of heart failure. Patients who received inappropriate shocks were more likely to have advanced symptoms of heart failure (NYHA class III or IV) than those who did not receive spurious shocks (63% vs 42%, p ⫽ 0.026). Also, compared with patients with no shocks, patients who received inappropriate ICD shocks were more likely to have atrial fibrillation (AF) on their baseline surface electrocardiograms (28% vs 15%, p ⫽ 0.07) and less likely to have a history of coronary disease (63% vs 77%, p ⫽ 0.07). A total of 42 inappropriate shocks were delivered in 32 patients during the same median follow-up of 501 days. Of these 32 patients, 7 received 2 and 1 received 3 inappropriate shocks. These spurious ICD shocks were due to AF or tachycardia (n ⫽ 31), other supraventricular tachycardias (n ⫽ 6), sinus tachycardia (n ⫽ 3), and noise or double counting (n ⫽ 2). The type of device implanted (single chamber [n ⫽ 37], dual chamber with [n ⫽ 29] or without [n ⫽ 164] biventricular pacing) did not affect the incidence of inappropriate shocks. Of note, only 8% of patients had their rhythm discrimination algorithms (onset and stability) programmed on, at the discretion of the implanting physicians. The mean rate cutoff for ICD therapy was marginally less in patients receiving inappropriate shocks (166 vs 174 beats/min, p ⫽ 0.079), but this did not reach statistical significance. Time to first inappropriate shock was defined as the time from ICD implantation to the first day of inappropriate shock. The severity of symptoms of heart failure was a strong predictor of the time to first inappropriate ICD shock. The 1- and 2-year Kaplan-Meier estimates of the incidence
Figure 1. Kaplan-Meier curves showing time to first inappropriate ICD shock in patients with heart failure in NYHA class I or II compared with NYHA class III or IV.
Figure 2. Bar graph comparing the incidence of inappropriate ICD shocks between patients with AF and those without AF on the baseline surface electrocardiogram obtained before device implantation. The p value is adjusted for the presence of other covariates in a Cox proportional-hazards multivariate model.
of first inappropriate ICD shock were 8% and 12%, respectively, for patients in NYHA class I or II compared with 21% and 30%, respectively, in those in NYHA class III or IV (p ⫽ 0.02). The mean time to first inappropriate ICD shock was 990 ⫾ 32 days in patients in NYHA class I or II compared with 924 ⫾ 56 days in those in NYHA class III or IV (p ⫽ 0.02). Kaplan-Meier estimates of the probability curves were constructed for this comparison and are shown in Figure 1. The effect of heart failure severity on the time to first inappropriate ICD shock was also analyzed in a Cox proportional-hazards regression model. After correcting for age, gender, indication for ICD implantation, width of QRS interval, the presence of AF, the absence of coronary disease, and the use of  blockers, NYHA classification was found to be an independent predictor of the time to first inappropriate ICD shock (hazard ratio 2.7 for NYHA classes III and IV compared with classes I and II, p ⫽ 0.01).
546
The American Journal of Cardiology (www.AJConline.org)
Table 2 Multivariate analysis of the predictors of time to first inappropriate defibrillator shock Variable NYHA class III/IV versus I/II Age per 1-yr increase Gender (female vs male) ICD indication (secondary vs primary) QRS (per 1-ms increase in width) Absence of coronary artery disease Presence of AF Treatment with  blockers
Hazard Ratio
95% Confidence Interval
p Value
2.768
1.277–6.001
0.010
1.010 0.766 1.236
0.984–1.037 0.337–1.741 0.540–2.831
0.460 0.524 0.616
0.992
0.981–1.002
0.123
2.612
1.178–5.792
0.018
2.448 2.054
1.059–5.659 0.852–4.954
0.036 0.109
In addition, the presence of AF at the time of ICD implantation (Figure 2) and the absence of coronary disease were found to be significant independent predictors of the time to the first inappropriate ICD shock (hazard ratio 2.4, p ⫽ 0.04 for AF, and hazard ratio 2.6, p ⫽ 0.02 for the absence of coronary disease). Table 2 lists the results of the Cox regression analysis. •••
Our data demonstrate that patients with severe symptoms of heart failure as reflected by their NYHA classifications are more likely to receive inappropriate ICD shocks within a mean follow-up of about 16 months from the date of initial device implantation. This association between the severity of heart failure and the time to first spurious ICD shock was independent of other potential covariates, such as the age or gender of the patient, the indication for ICD implantation, electrocardiographic parameters, such as the width of the QRS complex or the presence of AF, the presence of coronary disease, or pharmacologic treatment with  blockers. This finding might have significant clinical implications for patients with advanced heart failure and their managing physicians, such as the early consideration of treatment with antiarrhythmic medications before or soon after device implantation. The recently presented but yet unpublished results of the Optical Pharmacological Therapy in Implantable Cardioverter Defibrillator Patients trial suggest a possible role for the prophylactic use of amiodarone in patients with ICDs. Also, given that patients with inappropriate ICD shocks were more likely to have AF as their baseline rhythm, consideration should also be given to early atrioventricular nodal ablation, especially in the subset of patients with rapid ventricular response rates despite pharmacologic treatment or those intolerant to drugs. Our finding of the increased frequency of inappropriate ICD shocks in patients with severe heart failure is in keeping with other reports, although scarce. Nanthakumar et al11 demonstrated a similar relation between the severity of heart failure and the incidence of inappropriate shocks in a pop-
ulation of patients with single-chamber devices only. The investigators concluded that an upgrade to a dual-chamber ICD with better rhythm discrimination algorithms could potentially reduce the number of inappropriate shocks. Our study population, in contrast, included patients with singleand dual-chamber ICDs, with no documented differences between these 2 groups in the likelihood of receiving an inappropriate ICD shock. Given that only 8.3% of the patients in our study had devices with rhythm discrimination algorithms turned on, it is very hard to draw any definitive conclusions as to the benefit s of these algorithms in a heart failure population. The effect of dual- versus single-chamber devices as well as the programming of the ICD parameters as it pertains to the therapy rate cutoffs, the detection times, and the rhythm discrimination algorithms deserves further investigation. Advanced symptoms of heart failure predict an increased risk for inappropriate ICD shocks. Larger studies are needed to confirm this relation and to identify the means of preventing inappropriate ICD shocks in patients with heart failure. 1. Nunain SO, Roelke M, Trouton T, Osswald S, Kim YH, Sosa-Suarez G, Brooks DR, McGovern B, Guy M, Torchiana DF, et al. Limitations and late complications of third generation automatic cardioverter defibrillators. Circulation 1995;91:2204 –2213. 2. Wood MA, Stambler BS, Damiano RJ, Greenway P, Ellenbogen KA. Lessons learned from data logging in a multicenter clinical trial using a late generation implantable cardioverter defibrillator. The Guardian ATP 4210 Multicentre Investigators Group. J Am Coll Cardiol 1994;24:1692– 1699. 3. Grimm W, Flores BF, Marchilinski FE. Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable defibrillators. Pacing Clin Electrophysiol 1992;15:1667–1673. 4. Rosenqvist M, Beyer T, Block M, den Dulk K, Minten J, Lindemans F. Adverse events with transvenous table cardioverter-defibrillators: a prospective multicenter study. European Jewel ICD Investigators. Circulation 1998;98:663– 670. 5. McCready MJ, Exner DV. Quality of life and psychological impact of implantable cardioverter defibrillators: focus on randomized controlled trial data. Card Electrophysiol Rev 2003;7:63–70. 6. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341:1882–1890. 7. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933–1940. 8. Connolly S, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O’Brien B. Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297–1302. 9. Moss AJ, Zareba W, Hall J, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877– 883. 10. Seidl K, Senges J. Worldwide utilization of implantable cardioverter/ defibrillators now and in the future. Card Electrophysiol Rev 2003;1:5–13. 11. Nanthakumar K, Dorian P, Paquette M, Greene M, Edwards J, Heng D, Noble J, Newman D. Is inappropriate implantable defibrillator shock therapy predictable? J Intervent Card Electrophyiol 2003;8:215–229.