Sudden cardiac death post arrest care and prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The optimal approach to prevention of SCD following ST elevation MI (STEMI) has been evaluated in multiple randomized trials. In general, post-STEMI patients should be treated with evidenced based therapies that have been associated with a reduction in SCD including beta-blockers, ACE-inhibitors (or ARBs in patients who are ACE intolerant) and statins. In patients who have symptomatic congestive heart failure (CHF), an aldosterone antagonist may be a reasonable additional therapy. Despite the intuitive benefits of anti-arrhythmics, amiodarone and sotalol have not been shown to reduce all cause mortality following STEMI, although amiodarone may be useful in reducing the frequency of shocks in patients with ICDs who have unacceptably high rates of shock. In general terms, ICD placement is indicated in those patients with a reduced left ventricular ejection fraction at 40 days post MI and / or 3 months following revascularization (PCI or CABG) for STEMI given the survival benefits in this population.

Post Arrest Care and Prevention

Timing of Sudden Cardiac Death Following ST elevation MI

Patients with STEMI are at risk of sudden cardiac death. The timing of sudden cardiac death following STEMI is as follows:

  • In the first 3 months after STEMI one quarter of sudden cardiac deaths occur. This statistic is critical in so far as implantable cardiac defibrillators are often not implanted in the first three months. It is for this reason that wearable defibrillators are sometimes used in patients with a large MI and reduced ejection fraction.
  • In the first year following STEMI one half of the sudden cardiac deaths occur.
  • Beyond one year, there is still an increased risk of sudden cardiac death for a prolonged period of time.

Medical Therapy to Prevent Sudden Death Following STEMI

Therapies aimed to reduce disease progression, stabilize plaque, improve left ventricular function, and reduce ischemia may minimize the risk of sudden cardiac death. These therapies include beta blockade, ACE inhibition, and statins.

Beta Blockers

Beta blocker administration has been associated with a reduction in sudden cardiac death from 5.0% to 3.3% in a review of 13 trials [1]. The reduction in SCD was greatest among patients with congestive heart failure. Among patients with an ICD, beta blocker administration has been associated with an additional reduction in mortality in MADIT II (hazard ratio of 0.42 to 0.44) and a lower frequency of ICD discharge (hazard ratio of 0.48) [2].

ACE Inhibitor

ACE inhibitor administration has been associated with a 20% relative and a 1.4% absolute reduction in the risk of SCD in a metanalysis of randomized trials[3] .

Angiotensin II Receptor Blockers (ARBs)

If a patient is intolerant to ACE inhibitor, an ARB can be administered. Valsartan is non-inferior to captopril in reducing post MI mortality, and may therefore confer similar benefits in SCD [4].

Statin Therapy

Among patients with an ICD implanted, statin administration has been associated with a reduction in documented arrhythmias post-MI in observation studies [5] [6].

Aldosterone Antagonists

In the EPHESUS trial, among the specific subgroup of post MI patients who have left ventricular dysfunction and / or diabetes, eplerenone administration was associated with reduction in all cause and SCD mortality (4.9% vs 6.1%)[7].

Anti-arrhythmics

Despite the intuitive benefits of anti-arrhythmic treatments, anti-arrhythmics have not shown a reduction in all cause mortality in the management of post MI SCD. Amiodarone was associated with a reduction in arrhythmic death among patients with an LVEF of <40% following STEMI, but all cause mortality was not improved in the CAMIAT [8] [9] trial. Anti-arrhythmics such as amiodarone may be useful in reducing the frequency of shocks in patients with an ICD who have excessively frequent shocks. Flecainide and propafenone should not be administered as these Class I C agents are proarrhythmic in patients with coronary artery disease [10].

Induced Hypothermia to Improve Neurological Outcome

Clinical practice guidelines summarize management.[11]

A systematic review by the Cochrane Collaboration suggests benefit.[12] A second systematic review focusing on survivors of non-shockable rhythms suggests benefit.[13]

Patients surviving cardiac arrest who cannot follow commands[14] or who are comatose[15], may have increased chance of favorable neurological outcome if their body temperature is cooled to 32 to 34 degrees centigrade.

Prevention of Sudden Death and Implantable Cardioverter Defibrillators Following STEMI

In general terms, ICD placement is indicated in those patients with a reduced left ventricular ejection fraction at 40 days post MI and / or 3 months following revascularization (PCI or CABG) for STEMI given the survival benefits in this population. Patients should also be treated with evidence based therapies including beta-blockers, ACE inhibitors and statins. Patients undergoing ICD implantation should not have a limited life expectancy due to non-cardiovascular causes.

Consensus and CMS Indications for ICD Placement

The following are clear Grade 1 A or CMS supported recommendations for placement of an ICD:

  • Based upon the MADIT II study entry criteria, patients with a prior MI and an LVEF of < 30% should be treated with an ICD after 40 days. This is true whether or not the patient is inducible on electrophysiologic testing.
  • Based upon the SCD-Heft study entry criteria, patients with an ischemic cardiomyopathy who are symptomatic with NYHA grade II or III CHF with an LVEF < 35%. Again, This is true whether or not the patient is inducible on electrophysiologic testing.
  • Some patients will not have an LVEF as low as < 30% as in MADIT II or as low as an LVEF < 35% as in SCD-HeFT, but if they have an LVEF < 40%, and non sustained ventricular tachycardia on Holter monitoring and are inducible on EP testing, then they are appropriate candidates for ICD placement based upon the MUSTT and MADIT I trials.
  • Based upon the MADIT I study entry criteria, patients with a history of MI with an LVEF < 35% who have inducible VT or VF on electrophysiologic testing at least 4 weeks after STEMI.
  • Patients who meet the COMPANION criteria who have an indication for a cardiac resynchronization (CRT) device and have NYHA class IV congestive heart failure (CHF)

Timing of ICD Placement

Despite the fact that the highest risk of SCD is in the first 3 months after STEMI, the DINAMIT [16] and IRIS [17] trials did not show a benefit of ICD placement during the first 3 months after STEMI. Likewise, it should be noted that MADITT II [18] excluded patients who had an MI or revascularization within the preceding 40 days. The results of DINAMIT and IRIS form the basis for the guidelines recommendation that ICD implantation be deferred until 40 days following STEMI. In DINAMIT, 332 patients were enrolled if they had an MI in the previous 6 to 40 days (the average time of implantation was 18 days following MI) and their LVEF was < 35%. A heart rate > 80 beats per minute or a reduced heart rate variability was required. At 30 days of follow-up, the all cause mortality was 7.5% in ICD patients and 6.9% in placebo patients (p=NS). Non-arrhythmic deaths were more common in the ICD arm, and arrhythmic deaths were more common in the placebo arm. Similar trends in mortality were observed in the subsequent IRIS trial, which enrolled a larger number of patients (n=898), during a similar period following STEMI (5 to 31 days) with 37 months of follow-up.

There are some differences in society and CMS recommendations regarding the timing of ICD placement. CMS recommends that LVEF be assessed at 3 months following the most recent revascularization. In contrast to the CMS guidance, the 2008 American College of Cardiology / American Heart Association /Heart Rhythm Society guidelines recommend a 40 day delay following a STEMI and there is no recommendation regarding a 3 month delay following revascularization.

Management of the Patient While Awaiting ICD Placement

Evidence based treatment with beta-blockers, statins, and ACE-inhibitors should be administered to patients while they await placement of an ICD at 40 days to 3 months following STEMI. An external cardiac defibrillator vest can be prescribed in high risk patients with a low ejection fraction while the patient is awaiting assessment of their LVEF at 3 months.

Role of Electrophysiology Testing

Inducibiity and pharmacologic suppression of VT/VF on electrophysiologic studies is no longer deemed to be relevant based upon the MUSTT study [19] and the MADITT I study [20]. Importantly, lack of inducibility on electrophysiologic testing should not preclude implantation of an ICD.

ICD Implantation in Patients with Chronic Stable Symptomatic Congestive Heart Failure: The SCD-HeFT Trial

While the previous trials such as MADITT, MUST, IRIS and DANIMIT focused on post MI patients, the SCD-HeFT trial instead focused on a different population, namely patients with chronic stable symptomatic congestive heart failure (CHF) due to either ischemic or nonischemic cardiomyopathy [25]. In contrast to previous studies where only a reduced ejection fraction was required, in SCD-HeFT symptoms of CHF (NYHA class II or III) were required along with an LVEF of < 35%. For instance, it should be noted that only about two thirds of patients in MADIT II had symptoms of heart failure. ICD implantation was associated with a reduction in mortality at 5 years versus placebo (29% versus 36%), with similar benefits observed both in patients with ischemic and non-ischemic cardiomyopathy. The third arm, amiodarone therapy, was not associated with a reduction in mortality. Based upon SCD-HeFT, an ICD is indicated in patients with an ischemic cardiomyopathy with NYHA class II – III CHF and an LVEF < 35%.

The Benefit of ICD Implantation May Be Greater in Patients with a QRS Duration > 120 msec

In both SCD-HeFT and MADIT II, the reduction in SCD was greater in patients with a QRS duration > 120 msec.

Wearable Defibrillators

In patients with a large MI with a low EF who are awaiting permanent ICD implantation, use of a wearable defibrillator is a reasonable strategy.

Cardiac resynchronization therapy (CRT) Combined with ICD Placement

Patients with congestive heart failure following MI may have dyssynchrony or a loss of coordinated contraction in the left ventricle. Restoration of synchronous contraction can improve patient symptoms and may improve left ventricular function and even mortality in appropriate patients. It is notable that the indications for CRT placement are similar to those for ICD placement, and some patients may benefit from a combined device that functions in both capacities.

Although there are no clear guidelines recommendations, based upon the results of the COMPANION trial it is reasonable to place a combined ICD / CRT device in patients with the following:

  • Symptomatic NYHA Class III or IV congestive heart failure
  • A left ventricular ejection fraction < 35%
  • Evidence of left ventricular dyssynchrony with a QRS > 120 msec

Unresolved Questions in Identifying the Optimal Patients for ICD Implanatation Following STEMI

The benefits of ICD placement in those patients over the age of 75 and in those with impaired renal function is not well defined, but post-hoc analyses from randomized trials suggest a lack of benefit in these populations. Non-sustained VT on Holter monitoring, an abnormal signal averaged EKG, and abnormal micro T wave alternans are associated with an increased risk of SCD, however, it is not known if ICD therapy is of benefit in these populations.

2008 ACC/AHA/HRS Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities (DO NOT EDIT) [21]

Implantable Cardioverter Defibrillators (DO NOT EDIT) [21]

Class I
"1. ICD therapy is indicated in patients who are survivors of cardiac arrest due to VF or hemodynamically unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes.[22][23][24][25][26][27][28] (Level of Evidence: A). "
"2. ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable.[22][23][24][25][26][27][28] (Level of Evidence: B)"
"3. ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological study.[22][26] (Level of Evidence: B)"
"4. ICD therapy is indicated in patients with LVEF less than 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III.[22][29] (Level of Evidence: A). "
"5. ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III.[22][29][30][31] (Level of Evidence: B)"
"6. ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF less than 30%, and are in NYHA functional Class I.[22][18] (Level of Evidence: A). "
"7. ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than 40%, and inducible VF or sustained VT at electrophysiological study.[22][20][19] (Level of Evidence: B)"
Class III
"1. ICD therapy is not indicated for patients who do not have a reasonable expectation of survival with an acceptable functional status for at least 1 year, even if they meet ICD implantation criteria specified in the Class I, IIa, and IIb recommendations above. (Level of Evidence: C)"
"2. ICD therapy is not indicated for patients with incessant VT or VF. (Level of Evidence: C)"
"3. ICD therapy is not indicated in patients with significant psychiatric illnesses that may be aggravated by device implantation or that may preclude systematic follow-up. (Level of Evidence: C)"
"4. ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not candidates for cardiac transplantation or CRT-D. (Level of Evidence: C)"
"5. ICD therapy is not indicated for syncope of undetermined cause in a patient without inducible ventricular tachyarrhythmias and without structural heart disease. (Level of Evidence: C)"
"6. ICD therapy is not indicated when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias associated with the Wolff-Parkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease). (Level of Evidence: C)"
"7. ICD therapy is not indicated for patients with ventricular tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma).[22] (Level of Evidence: B)"
Class IIa
"1. ICD implantation is reasonable for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM. (Level of Evidence: C)"
"2. ICD implantation is reasonable for patients with sustained VT and normal or near-normal ventricular function. (Level of Evidence: C)"
"3. ICD implantation is reasonable for patients with HCM who have 1 or more major{dagger} risk factors for SCD. (Level of Evidence: C)"
"4. ICD implantation is reasonable for the prevention of SCD in patients with ARVD/C who have 1 or more risk factors for SCD. (Level of Evidence: C)"
"5. ICD implantation is reasonable to reduce SCD in patients with long-QT syndrome who are experiencing syncope and/or VT while receiving beta blockers.[32][33][34][35][36] (Level of Evidence: B)"
"6. ICD implantation is reasonable for non hospitalized patients awaiting transplantation. (Level of Evidence: C)"
"7. ICD implantation is reasonable for patients with Brugada syndrome who have had syncope. (Level of Evidence: C)"
"8. ICD implantation is reasonable for patients with Brugada syndrome who have documented VT that has not resulted in cardiac arrest. (Level of Evidence: C)"
"9. ICD implantation is reasonable for patients with catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta blockers. (Level of Evidence: C)"
"10. ICD implantation is reasonable for patients with cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. (Level of Evidence: C)"
Class IIb
"1. ICD therapy may be considered in patients with nonischemic heart disease who have an LVEF of less than or equal to 35% and who are in NYHA functional Class I. (Level of Evidence: C)"
"2. ICD therapy may be considered for patients with long-QT syndrome and risk factors for SCD. (Level of Evidence: B)"
"3. ICD therapy may be considered in patients with syncope and advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to define a cause. (Level of Evidence: C)"
"4. ICD therapy may be considered in patients with a familial cardiomyopathy associated with sudden death. (Level of Evidence: C)"
"5. ICD therapy may be considered in patients with LV noncompaction. (Level of Evidence: C)"

Implantable Cardioverter-Defibrillators in Pediatric Patients and Patients With Congenital Heart Disease (DO NOT EDIT) [21]

Class I
"1. ICD implantation is indicated in the survivor of cardiac arrest after evaluation to define the cause of the event and to exclude any reversible causes.[37][38][39][40] (Level of Evidence: B)"
"2. ICD implantation is indicated for patients with symptomatic sustained VT in association with congenital heart disease who have undergone hemodynamic and electrophysiological evaluation. Catheter ablation or surgical repair may offer possible alternatives in carefully selected patients.[41] (Level of Evidence: C)"
Class III
"1. All Class III recommendations found in Section 3, "Indications for Implantable Cardioverter-Defibrillator Therapy," apply to pediatric patients and patients with congenital heart disease, and ICD implantation is not indicated in these patient populations. (Level of Evidence: C)"
Class IIa
"1. ICD implantation is reasonable for patients with congenital heart disease with recurrent syncope of undetermined origin in the presence of either ventricular dysfunction or inducible ventricular arrhythmias at electrophysiological study.[42][43] (Level of Evidence: B)"
Class IIb
"1. ICD implantation may be considered for patients with recurrent syncope associated with complex congenital heart disease and advanced systemic ventricular dysfunction when thorough invasive and noninvasive investigations have failed to define a cause.[44][45] (Level of Evidence: C)"

References

  1. ↑ Nuttall SL, Toescu V, Kendall MJ (2000). "beta Blockade after myocardial infarction. Beta blockers have key role in reducing morbidity and mortality after infarction". BMJ (Clinical Research Ed.). 320 (7234): 581. PMC 1117610. PMID 10688573. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  2. ↑ Brodine WN, Tung RT, Lee JK, Hockstad ES, Moss AJ, Zareba W, Hall WJ, Andrews M, McNitt S, Daubert JP (2005). "Effects of beta-blockers on implantable cardioverter defibrillator therapy and survival in the patients with ischemic cardiomyopathy (from the Multicenter Automatic Defibrillator Implantation Trial-II)". The American Journal of Cardiology. 96 (5): 691–5. doi:10.1016/j.amjcard.2005.04.046. PMID 16125497. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  3. ↑ Domanski MJ, Exner DV, Borkowf CB, Geller NL, Rosenberg Y, Pfeffer MA (1999). "Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials". Journal of the American College of Cardiology. 33 (3): 598–604. PMID 10080457. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  4. ↑ Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM (2003). "Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both". The New England Journal of Medicine. 349 (20): 1893–906. doi:10.1056/NEJMoa032292. PMID 14610160. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  5. ↑ Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP (2003). "Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial". Journal of the American College of Cardiology. 42 (1): 81–7. PMID 12849664. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  6. ↑ Dickinson MG, Ip JH, Olshansky B, Hellkamp AS, Anderson J, Poole JE, Mark DB, Lee KL, Bardy GH (2007). "Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)". American Heart Journal. 153 (4): 573–8. doi:10.1016/j.ahj.2007.02.002. PMID 17383296. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  7. ↑ Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M (2003). "Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction". The New England Journal of Medicine. 348 (14): 1309–21. doi:10.1056/NEJMoa030207. PMID 12668699. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  8. ↑ Cairns JA, Connolly SJ, Roberts R, Gent M (1997). "Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators". Lancet. 349 (9053): 675–82. PMID 9078198. Retrieved 2011-02-04. Unknown parameter |month= ignored (help)
  9. ↑ Farré J, Romero J, Rubio JM, Ayala R, Castro-Dorticós J (1999). "Amiodarone and "primary" prevention of sudden death: critical review of a decade of clinical trials". The American Journal of Cardiology. 83 (5B): 55D–63D. PMID 10089841. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  10. ↑ Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL (1991). "Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial". The New England Journal of Medicine. 324 (12): 781–8. doi:10.1056/NEJM199103213241201. PMID 1900101. Retrieved 2011-02-07. Unknown parameter |month= ignored (help)
  11. ↑ ECC Committee, Subcommittees and Task Forces of the American Heart Association (2005). "2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 112 (24 Suppl): IV1–203. doi:10.1161/CIRCULATIONAHA.105.166550. PMID 16314375.
  12. ↑ Arrich J, Holzer M, Havel C, Müllner M, Herkner H (2012). "Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation". Cochrane Database Syst Rev. 9: CD004128. doi:10.1002/14651858.CD004128.pub3. PMID 22972067.
  13. ↑ Kim YM, Yim HW, Jeong SH, Klem ML, Callaway CW (2012). "Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies". Resuscitation. 83 (2): 188–96. doi:10.1016/j.resuscitation.2011.07.031. PMID 21835145.
  14. ↑ Hypothermia after Cardiac Arrest Study Group (2002). "Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest". N Engl J Med. 346 (8): 549–56. doi:10.1056/NEJMoa012689. PMID 11856793. Review in: ACP J Club. 2002 Sep-Oct;137(2):46 Review in: Evid Based Nurs. 2002 Oct;5(4):111
  15. ↑ Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G; et al. (2002). "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia". N Engl J Med. 346 (8): 557–63. doi:10.1056/NEJMoa003289. PMID 11856794.
  16. ↑ Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ (2004). "Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction". The New England Journal of Medicine. 351 (24): 2481–8. doi:10.1056/NEJMoa041489. PMID 15590950. Retrieved 2011-02-04. Unknown parameter |month= ignored (help)
  17. ↑ Steinbeck G, Andresen D, Seidl K, Brachmann J, Hoffmann E, Wojciechowski D, Kornacewicz-Jach Z, Sredniawa B, Lupkovics G, Hofgärtner F, Lubinski A, Rosenqvist M, Habets A, Wegscheider K, Senges J (2009). "Defibrillator implantation early after myocardial infarction". The New England Journal of Medicine. 361 (15): 1427–36. doi:10.1056/NEJMoa0901889. PMID 19812399. Retrieved 2011-02-04. Unknown parameter |month= ignored (help)
  18. ↑ 18.0 18.1 Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML (2002). "Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction". The New England Journal of Medicine. 346 (12): 877–83. doi:10.1056/NEJMoa013474. PMID 11907286. Retrieved 2011-02-04. Unknown parameter |month= ignored (help)
  19. ↑ 19.0 19.1 Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G (1999). "A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators". The New England Journal of Medicine. 341 (25): 1882–90. doi:10.1056/NEJM199912163412503. PMID 10601507. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  20. ↑ 20.0 20.1 Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M (1996). "Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators". The New England Journal of Medicine. 335 (26): 1933–40. doi:10.1056/NEJM199612263352601. PMID 8960472. Retrieved 2011-02-06. Unknown parameter |month= ignored (help)
  21. ↑ 21.0 21.1 21.2 Epstein AE, DiMarco JP, Ellenbogen KA; et al. (2008). "ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons". Circulation. 117 (21): e350–408. PMID 18483207. Text "doi:10.1161/CIRCUALTIONAHA.108.189742 " ignored (help); Unknown parameter |month= ignored (help)
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL (2006). "ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)". Journal of the American College of Cardiology. 48 (5): e247–346. doi:10.1016/j.jacc.2006.07.010. PMID 16949478. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  23. ↑ 23.0 23.1 "A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators". The New England Journal of Medicine. 337 (22): 1576–83. 1997. doi:10.1056/NEJM199711273372202. PMID 9411221. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  24. ↑ 24.0 24.1 Wever EF, Hauer RN, van Capelle FL, Tijssen JG, Crijns HJ, Algra A, Wiesfeld AC, Bakker PF, Robles de Medina EO (1995). "Randomized study of implantable defibrillator as first-choice therapy versus conventional strategy in postinfarct sudden death survivors". Circulation. 91 (8): 2195–203. PMID 7697849. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  25. ↑ 25.0 25.1 Siebels J, Kuck KH (1994). "Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg)". American Heart Journal. 127 (4 Pt 2): 1139–44. PMID 8160593. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  26. ↑ 26.0 26.1 26.2 Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B (2000). "Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone". Circulation. 101 (11): 1297–302. PMID 10725290. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  27. ↑ 27.0 27.1 Kuck KH, Cappato R, Siebels J, Rüppel R (2000). "Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH)". Circulation. 102 (7): 748–54. PMID 10942742. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  28. ↑ 28.0 28.1 "eurheartj.oxfordjournals.org" (PDF). Retrieved 2012-11-05.
  29. ↑ 29.0 29.1 Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH (2005). "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure". The New England Journal of Medicine. 352 (3): 225–37. doi:10.1056/NEJMoa043399. PMID 15659722. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  30. ↑ Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH (2004). "Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy". The New England Journal of Medicine. 350 (21): 2151–8. doi:10.1056/NEJMoa033088. PMID 15152060. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  31. ↑ Desai AS, Fang JC, Maisel WH, Baughman KL (2004). "Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials". JAMA : the Journal of the American Medical Association. 292 (23): 2874–9. doi:10.1001/jama.292.23.2874. PMID 15598919. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  32. ↑ Zareba W, Moss AJ, Daubert JP, Hall WJ, Robinson JL, Andrews M (2003). "Implantable cardioverter defibrillator in high-risk long QT syndrome patients". Journal of Cardiovascular Electrophysiology. 14 (4): 337–41. PMID 12741701. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  33. ↑ Viskin S (2003). "Implantable cardioverter defibrillator in high-risk long QT syndrome patients". Journal of Cardiovascular Electrophysiology. 14 (10): 1130–1, reply 1131. PMID 14521674. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  34. ↑ Goel AK, Berger S, Pelech A, Dhala A (2004). "Implantable cardioverter defibrillator therapy in children with long QT syndrome". Pediatric Cardiology. 25 (4): 370–8. doi:10.1007/s00246-003-0566-4. PMID 14994181. Retrieved 2012-11-05.
  35. ↑ Goldenberg I, Mathew J, Moss AJ, McNitt S, Peterson DR, Zareba W, Benhorin J, Zhang L, Vincent GM, Andrews ML, Robinson JL, Morray B (2006). "Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification". Journal of the American College of Cardiology. 48 (5): 1047–52. doi:10.1016/j.jacc.2006.06.033. PMID 16949500. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  36. ↑ Hobbs JB, Peterson DR, Moss AJ, McNitt S, Zareba W, Goldenberg I, Qi M, Robinson JL, Sauer AJ, Ackerman MJ, Benhorin J, Kaufman ES, Locati EH, Napolitano C, Priori SG, Towbin JA, Vincent GM, Zhang L (2006). "Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome". JAMA : the Journal of the American Medical Association. 296 (10): 1249–54. doi:10.1001/jama.296.10.1249. PMID 16968849. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  37. ↑ Silka MJ, Kron J, Dunnigan A, Dick M (1993). "Sudden cardiac death and the use of implantable cardioverter-defibrillators in pediatric patients. The Pediatric Electrophysiology Society". Circulation. 87 (3): 800–7. PMID 8443901. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  38. ↑ Hamilton RM, Dorian P, Gow RM, Williams WG (1996). "Five-year experience with implantable defibrillators in children". The American Journal of Cardiology. 77 (7): 524–6. PMID 8629596. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  39. ↑ Alexander ME, Cecchin F, Walsh EP, Triedman JK, Bevilacqua LM, Berul CI (2004). "Implications of implantable cardioverter defibrillator therapy in congenital heart disease and pediatrics". Journal of Cardiovascular Electrophysiology. 15 (1): 72–6. doi:10.1046/j.1540-8167.2004.03388.x. PMID 15028076. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  40. ↑ Choi GR, Porter CB, Ackerman MJ (2004). "Sudden cardiac death and channelopathies: a review of implantable defibrillator therapy". Pediatric Clinics of North America. 51 (5): 1289–303. doi:10.1016/j.pcl.2004.04.015. PMID 15331285. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  41. ↑ Karamlou T, Silber I, Lao R, McCrindle BW, Harris L, Downar E, Webb GD, Colman JM, Van Arsdell GS, Williams WG (2006). "Outcomes after late reoperation in patients with repaired tetralogy of Fallot: the impact of arrhythmia and arrhythmia surgery". The Annals of Thoracic Surgery. 81 (5): 1786–93, discussion 1793. doi:10.1016/j.athoracsur.2005.12.039. PMID 16631673. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  42. ↑ Mushlin AI, Hall WJ, Zwanziger J, Gajary E, Andrews M, Marron R, Zou KH, Moss AJ (1998). "The cost-effectiveness of automatic implantable cardiac defibrillators: results from MADIT. Multicenter Automatic Defibrillator Implantation Trial". Circulation. 97 (21): 2129–35. PMID 9626173. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  43. ↑ Khairy P, Landzberg MJ, Gatzoulis MA, Lucron H, Lambert J, Marçon F, Alexander ME, Walsh EP (2004). "Value of programmed ventricular stimulation after tetralogy of fallot repair: a multicenter study". Circulation. 109 (16): 1994–2000. doi:10.1161/01.CIR.0000126495.11040.BD. PMID 15051640. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  44. ↑ Kammeraad JA, van Deurzen CH, Sreeram N, Bink-Boelkens MT, Ottenkamp J, Helbing WA, Lam J, Sobotka-Plojhar MA, Daniels O, Balaji S (2004). "Predictors of sudden cardiac death after Mustard or Senning repair for transposition of the great arteries". Journal of the American College of Cardiology. 44 (5): 1095–102. doi:10.1016/j.jacc.2004.05.073. PMID 15337224. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)
  45. ↑ Dubin AM, Berul CI, Bevilacqua LM, Collins KK, Etheridge SP, Fenrich AL, Friedman RA, Hamilton RM, Schaffer MS, Shah M, Silka MJ, Van Hare GF, Kertesz NJ (2003). "The use of implantable cardioverter-defibrillators in pediatric patients awaiting heart transplantation". Journal of Cardiac Failure. 9 (5): 375–9. PMID 14583898. Retrieved 2012-11-02. Unknown parameter |month= ignored (help)

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