- Email: [email protected]
Evolution of the Implantable Cardioverter-Defibrillator⁎
Journal of the American College of Cardiology © 2012 by the American College of Cardiology Foundation Published by Elsevier Inc.
EDITORIAL COMMENT
Evolution of the Implantable Cardioverter-Defibrillator* From Bullets to BBs Roger A. Winkle, MD East Palo Alto and Redwood City, California
When his friend and colleague, Dr. Harry Heller, died suddenly due to ventricular tachycardia (VT), Dr. Michel Mirowski conceived the concept of the implantable defibrillator to prevent such tragedies (1). He moved his family from Israel to Baltimore and, collaborating with Dr. Morton Mower, developed the first implantable defibrillator. Criticisms from Dr. Bernard Lown (2), who was at that time a leader in ventricular arrhythmias and external defibrillation, caused Drs. Mirowski and Mower to devise sensing algorithms that would only deliver a shock when a patient was essentially dead from ventricular fibrillation (VF). Working with Dr. Stephen Heilman and his engineers at Intec Systems (Pittsburgh, Pennsylvania), the original implantable cardioverter-defibrillator (ICD) sensed malignant ventricular arrhythmias using electrograms obtained from the shocking leads, which were a spring coil in the superior vena cava and a patch applied directly to the epicardial surface of the heart via sternotomy or thoracotomy. See page 2399
The sensing circuit incorporated the “probability density function” (PDF), which measured the extent to which electrograms were sinusoidal (3). The PDF was specifically designed to detect only sinusoidal VF and not other arrhythmias such as supraventricular tachycardias (SVTs) and monomorphic VTs. By its design, PDF sensing eliminated all “inappropriate” shocks, including those due to a broken lead because the noise would not be sinusoidal. About the time Mirowski et al. (1) were designing the implantable defibrillator, the introduction of programmed stimulation to induce ventricular arrhythmias (4) and ambulatory electrocardiogram recordings that occasionally recorded actual sudden cardiac deaths demonstrated that many tachyarrhythmic sudden deaths began as sustained *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From Silicon Valley Cardiology, East Palo Alto, California; and Sequoia Hospital, Redwood City, California. Dr. Winkle is an investigator for Cardialen.
Vol. 60, No. 23, 2012 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2012.07.066
monomorphic VT, which only much later degenerated into sinusoidal VF. Therefore, the original ICD failed to recognize many fatal VTs, and some patients could still experience sudden cardiac death because their terminal malignant arrhythmia was not “sinusoidal enough” to trigger an ICD shock. In fact, the ventricular rhythm that resulted in the world’s first successful human defibrillation with an implanted device was not sensed by the PDF algorithm until almost 40 s after its induction. By that time, it was assumed the ICD was not going to work, and an external defibrillator was being charged to deliver a transthoracic shock for what appeared to be a failure of the implanted device. Fortunately, just as the patient was to be externally defibrillated, the PDF circuit sensed the rhythm, the device began charging, and it delivered a successful shock. The entire ICD program may never have gotten off the ground if that external shock had been given a few seconds earlier because the PDF sensing algorithm was too restrictive. Because the original ICD frequently failed to deliver a life-saving shock, I worked with Stanley Bach, an Intec engineer, to design a circuit to sense local bipolar ventricular electrograms from a separate sensing lead that allowed shocks to be delivered for any rapid rhythm (including both SVTs and VTs) that exceeded a pre-specified rate cutoff (5). This represented a radical philosophical as well as design change from the initial ICD. A separate sensing lead was required, and the philosophy was now that it was better to deliver an inappropriate shock than to fail to deliver an appropriate shock. This engineering and philosophical paradigm shift is singularly responsible for all subsequent inappropriate shocks. It is also responsible for the almost 100% delivery of necessary appropriate shocks if devices are properly programmed. The original ICD was nonprogrammable, and it was frequently necessary to change the generator when patients experienced SVTs that exceeded the rate cutoff. The original devices had neither bradycardia pacing nor antitachycardia pacing (ATP) capabilities and delivered a nonprogrammable high-energy shock using a monophasic truncated exponential waveform. Benjamin Pless and Michael Sweeney, working at Ventritex (Sunnyvale, California), studied the pioneering animal work of Dr. John Schuder, who demonstrated that biphasic defibrillation waveforms were superior to the truncated exponential monophasic waveform (6). We tested the first biphasic waveform for defibrillation in humans at the time of ICD implantation. Despite the obvious superiority of the biphasic to the monophasic waveform, a manuscript reporting the results was rejected by 3 peer-reviewed journals before ultimate acceptance by Dr. Dean Mason, editor of the American Heart Journal (7). Despite reviewers’ comments that it was “not clinically relevant,” within a few years, there was not an implantable or external defibrillator manufactured that did not incorporate the biphasic waveform. Schuder’s biphasic waveform was included in the Ventritex
2400
Winkle Evolution of the ICD
Cadence device, which was the first modern ICD incorporating full programmability, bradycardia pacing, ATP, stored electrograms, and low-energy cardioversion in addition to high-energy defibrillation shocks. The incorporation of stored electrograms into the ICD made it possible for the first time to easily determine whether or not shocks were appropriate or inappropriate. In the early days, when ICDs were only used for secondary prevention, it was assumed that an occasional inappropriate shock was the price one paid to make certain patients always received an appropriate shock when needed, and there were few concerns about the risks of receiving a shock. The expansion of ICDs to primary prevention of sudden cardiac death resulted in large databases of patients who were followed in a prospective fashion. Studies in post-myocardial infarction patients with low ejection fractions (8) and those with congestive heart failure (9) discovered that both appropriate life-saving and inappropriate defibrillator shocks are associated with a worse long-term prognosis. It has proven elusive to determine whether defibrillator shocks are merely markers for clinical deterioration (e.g., declining left ventricular function or the occurrence of atrial fibrillation), which would result in increased mortality whether or not a device was implanted, or whether there is some detrimental effect such as subtle myocardial damage that results in increased mortality. Even if there is a detrimental effect of high-energy shocks, the appropriate delivery of an indicated shock far outweighs the potential harm from the device— hence the survival advantage for ICD therapy in most large randomized trials (10 –13). Regardless of whether they have an immediate live-saving beneficial effect or long-term detrimental impact on mortality, all high-energy shocks result in some degree of physical and psychological trauma for many patients. The number of appropriate shocks can be minimized by using longer detection delays to give the rhythm a chance to self-terminate and the use of more aggressive ATP before or during device charging (14). The number of inappropriate shocks for SVT can be minimized by increasing the rate cutoff, using dual-chamber sensing algorithms, and/or administering AV nodal blocking agents or antiarrhythmic drugs, or performing AV node ablation. In this issue of the Journal, Janardhan et al. (15) describe a novel electrotherapy to terminate VT with considerably lower energy than a biphasic shock. The method of energy delivery they describe may represent the first major change in the type of therapy delivered by an ICD since the introduction of the biphasic waveform over 20 years ago. The authors determined that each cycle length of VT has a phase-dependent “vulnerable point,” during which the VT can be terminated with an extremely low-energy shock (0.3 ⫾ 0.2 J). By delivering a series of very low-energy shocks throughout the VT cycle length, 1 of the shocks will be delivered at or near the point in the cardiac cycle where the lowest energy is required to terminate the arrhythmia. This has the potential to markedly reduce the total energy
JACC Vol. 60, No. 23, 2012 December 11, 2012:2399–401
required to terminate most VTs. Additional possible benefits of this therapy might include less discomfort to the patient, less subclinical myocardial damage, prolongation of battery life, and reduction in concerns about inappropriate shocks. There are numerous potential pitfalls to the ultimate adoption of this technology. It remains to be proven if it works reliably in human VT. It must also work properly under a variety of altered electrical milieus, including electrolyte imbalances, ischemic states, and in the presence of antiarrhythmic drugs. It also needs to be shown that a series of low-energy shocks does not result in significant discomfort to the patient. Although it does nothing to prevent inappropriate shocks, in theory if they do occur, the potential for discomfort and myocardial damage should be mitigated with this method of arrhythmia termination. It is unclear whether this technology would be applicable for terminating VF where the myocardium is not uniformly activated during a single cardiac cycle and there may not be a temporal variation in energy required to terminate the arrhythmia. Furthermore, fibrillatory rhythms do not have a single cycle length, which may make it difficult to determine the appropriate timing for delivery of a series of low-energy shocks. Despite these theoretical obstacles, these same authors have shown that a low-energy sequence of shocks can reliably terminate atrial fibrillation in an animal model (16). Sequential shock therapy for ventricular defibrillation is not new. A number of publications (17,18) in the 1980s and 1990s found a modest lowering of defibrillation energy with 2 or 3 sequential or overlapping shocks, often delivered using different shocking vectors. If this new arrhythmia termination technique proves successful in human arrhythmias, it could be a major advance in ICD therapy. It is possible that just as happened with John Schuder’s biphasic waveform, this novel electrotherapy concept will transition smoothly from the animal laboratory to patient care. It should be a relatively straightforward engineering task to incorporate this series of lowenergy pulses into currently available ICDs. We may well find that shooting a series of BBs at VT will result in the same termination success as a single high-energy bullet. Reprint requests and correspondence: Dr. Roger A. Winkle, Silicon Valley Cardiology, 1950 University Avenue, Suite 160, East Palo Alto, California 94303. E-mail: [email protected]. REFERENCES
1. Mirowski M, Mower MM, Staewen WS, Tabatznik B, Mendeloff AI. Standby automatic defibrillator. An approach to prevention of sudden coronary death. Arch Intern Med 1970;126:158 – 61. 2. Lown B, Axelrod P. Implanted standby defibrillators. Circulation 1972;46:637–9. 3. Langer A, Heilman MS, Mower MM, Mirowski M. Considerations in the development of the automatic implantable defibrillator. Med Instrum 1976;10:163–7. 4. Mason JW, Winkle RA. Accuracy of the ventricular tachycardiainduction study for predicting long-term efficacy and inefficacy of antiarrhythmic drugs. N Engl J Med 1980;303:1073–7.
Winkle Evolution of the ICD
JACC Vol. 60, No. 23, 2012 December 11, 2012:2399–401 5. Winkle RA, Bach SM Jr., Echt DS, et al. The automatic implantable defibrillator: local ventricular bipolar sensing to detect ventricular tachycardia and fibrillation. Am J Cardiol 1983;52:266 – 8. 6. Schuder JC, Gold JH, Stoeckle H, McDaniel WC, Cheung KN. Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 1983;30:415–22. 7. Winkle RA, Mead RH, Ruder MA, et al. Improved low energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform. Am Heart J 1989;117:122–7. 8. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II. J Am Coll Cardiol 2008;51:1357– 65. 9. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008;359:1009 –17. 10. The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576 – 83. 11. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882–90. 12. Moss AJ, Zareba W, Hall WJ, et al., for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877– 83. 13. Moss AJ, Hall WJ, Cannom DS, et al., for the Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with
14.
15.
16.
17.
18.
2401
an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933– 40. Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators. Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 2004;110:2591– 6. Janardhan AH, Li W, Fedorov VV, et al. A novel low-energy electrotherapy that terminates ventricular tachycardia with lower energy than a biphasic shock when antitachycardia pacing fails. J Am Coll Cardiol 2012;60:2393–8. Li W, Janardhan AH, Fedorov VV, Sha Q, Schuessler RB, Efimov IR. Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock. Circ Arrhythm Electrophysiol 2011;4:917–25. Jones DL, Sohi A, Bourland JD, Tacker WA, Kallok MJ, Klein GJ. Internal ventricular defibrillation with sequential pulse countershock in pigs: comparison with single pulses and effects of pulse separation. Pacing Clin Electrophysiol 1987;10:497–502. Chang MS, Inoue H, Kallok MJ, Zipes DP. Double and triple sequential shocks reduce ventricular defibrillation threshold in dogs with and without myocardial infarction. J Am Coll Cardiol 1986;8: 1393– 405.
Key Words: defibrillation y ICD y multistage electrotherapy y myocardial infarction y ventricular tachycardia.
EDITORIAL COMMENT
Evolution of the Implantable Cardioverter-Defibrillator* From Bullets to BBs Roger A. Winkle, MD East Palo Alto and Redwood City, California
When his friend and colleague, Dr. Harry Heller, died suddenly due to ventricular tachycardia (VT), Dr. Michel Mirowski conceived the concept of the implantable defibrillator to prevent such tragedies (1). He moved his family from Israel to Baltimore and, collaborating with Dr. Morton Mower, developed the first implantable defibrillator. Criticisms from Dr. Bernard Lown (2), who was at that time a leader in ventricular arrhythmias and external defibrillation, caused Drs. Mirowski and Mower to devise sensing algorithms that would only deliver a shock when a patient was essentially dead from ventricular fibrillation (VF). Working with Dr. Stephen Heilman and his engineers at Intec Systems (Pittsburgh, Pennsylvania), the original implantable cardioverter-defibrillator (ICD) sensed malignant ventricular arrhythmias using electrograms obtained from the shocking leads, which were a spring coil in the superior vena cava and a patch applied directly to the epicardial surface of the heart via sternotomy or thoracotomy. See page 2399
The sensing circuit incorporated the “probability density function” (PDF), which measured the extent to which electrograms were sinusoidal (3). The PDF was specifically designed to detect only sinusoidal VF and not other arrhythmias such as supraventricular tachycardias (SVTs) and monomorphic VTs. By its design, PDF sensing eliminated all “inappropriate” shocks, including those due to a broken lead because the noise would not be sinusoidal. About the time Mirowski et al. (1) were designing the implantable defibrillator, the introduction of programmed stimulation to induce ventricular arrhythmias (4) and ambulatory electrocardiogram recordings that occasionally recorded actual sudden cardiac deaths demonstrated that many tachyarrhythmic sudden deaths began as sustained *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From Silicon Valley Cardiology, East Palo Alto, California; and Sequoia Hospital, Redwood City, California. Dr. Winkle is an investigator for Cardialen.
Vol. 60, No. 23, 2012 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2012.07.066
monomorphic VT, which only much later degenerated into sinusoidal VF. Therefore, the original ICD failed to recognize many fatal VTs, and some patients could still experience sudden cardiac death because their terminal malignant arrhythmia was not “sinusoidal enough” to trigger an ICD shock. In fact, the ventricular rhythm that resulted in the world’s first successful human defibrillation with an implanted device was not sensed by the PDF algorithm until almost 40 s after its induction. By that time, it was assumed the ICD was not going to work, and an external defibrillator was being charged to deliver a transthoracic shock for what appeared to be a failure of the implanted device. Fortunately, just as the patient was to be externally defibrillated, the PDF circuit sensed the rhythm, the device began charging, and it delivered a successful shock. The entire ICD program may never have gotten off the ground if that external shock had been given a few seconds earlier because the PDF sensing algorithm was too restrictive. Because the original ICD frequently failed to deliver a life-saving shock, I worked with Stanley Bach, an Intec engineer, to design a circuit to sense local bipolar ventricular electrograms from a separate sensing lead that allowed shocks to be delivered for any rapid rhythm (including both SVTs and VTs) that exceeded a pre-specified rate cutoff (5). This represented a radical philosophical as well as design change from the initial ICD. A separate sensing lead was required, and the philosophy was now that it was better to deliver an inappropriate shock than to fail to deliver an appropriate shock. This engineering and philosophical paradigm shift is singularly responsible for all subsequent inappropriate shocks. It is also responsible for the almost 100% delivery of necessary appropriate shocks if devices are properly programmed. The original ICD was nonprogrammable, and it was frequently necessary to change the generator when patients experienced SVTs that exceeded the rate cutoff. The original devices had neither bradycardia pacing nor antitachycardia pacing (ATP) capabilities and delivered a nonprogrammable high-energy shock using a monophasic truncated exponential waveform. Benjamin Pless and Michael Sweeney, working at Ventritex (Sunnyvale, California), studied the pioneering animal work of Dr. John Schuder, who demonstrated that biphasic defibrillation waveforms were superior to the truncated exponential monophasic waveform (6). We tested the first biphasic waveform for defibrillation in humans at the time of ICD implantation. Despite the obvious superiority of the biphasic to the monophasic waveform, a manuscript reporting the results was rejected by 3 peer-reviewed journals before ultimate acceptance by Dr. Dean Mason, editor of the American Heart Journal (7). Despite reviewers’ comments that it was “not clinically relevant,” within a few years, there was not an implantable or external defibrillator manufactured that did not incorporate the biphasic waveform. Schuder’s biphasic waveform was included in the Ventritex
2400
Winkle Evolution of the ICD
Cadence device, which was the first modern ICD incorporating full programmability, bradycardia pacing, ATP, stored electrograms, and low-energy cardioversion in addition to high-energy defibrillation shocks. The incorporation of stored electrograms into the ICD made it possible for the first time to easily determine whether or not shocks were appropriate or inappropriate. In the early days, when ICDs were only used for secondary prevention, it was assumed that an occasional inappropriate shock was the price one paid to make certain patients always received an appropriate shock when needed, and there were few concerns about the risks of receiving a shock. The expansion of ICDs to primary prevention of sudden cardiac death resulted in large databases of patients who were followed in a prospective fashion. Studies in post-myocardial infarction patients with low ejection fractions (8) and those with congestive heart failure (9) discovered that both appropriate life-saving and inappropriate defibrillator shocks are associated with a worse long-term prognosis. It has proven elusive to determine whether defibrillator shocks are merely markers for clinical deterioration (e.g., declining left ventricular function or the occurrence of atrial fibrillation), which would result in increased mortality whether or not a device was implanted, or whether there is some detrimental effect such as subtle myocardial damage that results in increased mortality. Even if there is a detrimental effect of high-energy shocks, the appropriate delivery of an indicated shock far outweighs the potential harm from the device— hence the survival advantage for ICD therapy in most large randomized trials (10 –13). Regardless of whether they have an immediate live-saving beneficial effect or long-term detrimental impact on mortality, all high-energy shocks result in some degree of physical and psychological trauma for many patients. The number of appropriate shocks can be minimized by using longer detection delays to give the rhythm a chance to self-terminate and the use of more aggressive ATP before or during device charging (14). The number of inappropriate shocks for SVT can be minimized by increasing the rate cutoff, using dual-chamber sensing algorithms, and/or administering AV nodal blocking agents or antiarrhythmic drugs, or performing AV node ablation. In this issue of the Journal, Janardhan et al. (15) describe a novel electrotherapy to terminate VT with considerably lower energy than a biphasic shock. The method of energy delivery they describe may represent the first major change in the type of therapy delivered by an ICD since the introduction of the biphasic waveform over 20 years ago. The authors determined that each cycle length of VT has a phase-dependent “vulnerable point,” during which the VT can be terminated with an extremely low-energy shock (0.3 ⫾ 0.2 J). By delivering a series of very low-energy shocks throughout the VT cycle length, 1 of the shocks will be delivered at or near the point in the cardiac cycle where the lowest energy is required to terminate the arrhythmia. This has the potential to markedly reduce the total energy
JACC Vol. 60, No. 23, 2012 December 11, 2012:2399–401
required to terminate most VTs. Additional possible benefits of this therapy might include less discomfort to the patient, less subclinical myocardial damage, prolongation of battery life, and reduction in concerns about inappropriate shocks. There are numerous potential pitfalls to the ultimate adoption of this technology. It remains to be proven if it works reliably in human VT. It must also work properly under a variety of altered electrical milieus, including electrolyte imbalances, ischemic states, and in the presence of antiarrhythmic drugs. It also needs to be shown that a series of low-energy shocks does not result in significant discomfort to the patient. Although it does nothing to prevent inappropriate shocks, in theory if they do occur, the potential for discomfort and myocardial damage should be mitigated with this method of arrhythmia termination. It is unclear whether this technology would be applicable for terminating VF where the myocardium is not uniformly activated during a single cardiac cycle and there may not be a temporal variation in energy required to terminate the arrhythmia. Furthermore, fibrillatory rhythms do not have a single cycle length, which may make it difficult to determine the appropriate timing for delivery of a series of low-energy shocks. Despite these theoretical obstacles, these same authors have shown that a low-energy sequence of shocks can reliably terminate atrial fibrillation in an animal model (16). Sequential shock therapy for ventricular defibrillation is not new. A number of publications (17,18) in the 1980s and 1990s found a modest lowering of defibrillation energy with 2 or 3 sequential or overlapping shocks, often delivered using different shocking vectors. If this new arrhythmia termination technique proves successful in human arrhythmias, it could be a major advance in ICD therapy. It is possible that just as happened with John Schuder’s biphasic waveform, this novel electrotherapy concept will transition smoothly from the animal laboratory to patient care. It should be a relatively straightforward engineering task to incorporate this series of lowenergy pulses into currently available ICDs. We may well find that shooting a series of BBs at VT will result in the same termination success as a single high-energy bullet. Reprint requests and correspondence: Dr. Roger A. Winkle, Silicon Valley Cardiology, 1950 University Avenue, Suite 160, East Palo Alto, California 94303. E-mail: [email protected]. REFERENCES
1. Mirowski M, Mower MM, Staewen WS, Tabatznik B, Mendeloff AI. Standby automatic defibrillator. An approach to prevention of sudden coronary death. Arch Intern Med 1970;126:158 – 61. 2. Lown B, Axelrod P. Implanted standby defibrillators. Circulation 1972;46:637–9. 3. Langer A, Heilman MS, Mower MM, Mirowski M. Considerations in the development of the automatic implantable defibrillator. Med Instrum 1976;10:163–7. 4. Mason JW, Winkle RA. Accuracy of the ventricular tachycardiainduction study for predicting long-term efficacy and inefficacy of antiarrhythmic drugs. N Engl J Med 1980;303:1073–7.
Winkle Evolution of the ICD
JACC Vol. 60, No. 23, 2012 December 11, 2012:2399–401 5. Winkle RA, Bach SM Jr., Echt DS, et al. The automatic implantable defibrillator: local ventricular bipolar sensing to detect ventricular tachycardia and fibrillation. Am J Cardiol 1983;52:266 – 8. 6. Schuder JC, Gold JH, Stoeckle H, McDaniel WC, Cheung KN. Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 1983;30:415–22. 7. Winkle RA, Mead RH, Ruder MA, et al. Improved low energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform. Am Heart J 1989;117:122–7. 8. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II. J Am Coll Cardiol 2008;51:1357– 65. 9. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008;359:1009 –17. 10. The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576 – 83. 11. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882–90. 12. Moss AJ, Zareba W, Hall WJ, et al., for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877– 83. 13. Moss AJ, Hall WJ, Cannom DS, et al., for the Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with
14.
15.
16.
17.
18.
2401
an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933– 40. Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators. Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 2004;110:2591– 6. Janardhan AH, Li W, Fedorov VV, et al. A novel low-energy electrotherapy that terminates ventricular tachycardia with lower energy than a biphasic shock when antitachycardia pacing fails. J Am Coll Cardiol 2012;60:2393–8. Li W, Janardhan AH, Fedorov VV, Sha Q, Schuessler RB, Efimov IR. Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock. Circ Arrhythm Electrophysiol 2011;4:917–25. Jones DL, Sohi A, Bourland JD, Tacker WA, Kallok MJ, Klein GJ. Internal ventricular defibrillation with sequential pulse countershock in pigs: comparison with single pulses and effects of pulse separation. Pacing Clin Electrophysiol 1987;10:497–502. Chang MS, Inoue H, Kallok MJ, Zipes DP. Double and triple sequential shocks reduce ventricular defibrillation threshold in dogs with and without myocardial infarction. J Am Coll Cardiol 1986;8: 1393– 405.
Key Words: defibrillation y ICD y multistage electrotherapy y myocardial infarction y ventricular tachycardia.