EHRA Key References on Sudden death and ICDs

Defibrillator implantation early after myocardial infarction.
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; IRIS Investigators.
N Engl J Med. 2009 Oct 8;361(15):1427-36.

A prospective, randomized study showing that early ICD therapy after an acute myocardial infarction in patients at increased risk for SCD did not reduce overall mortality.

*** 2006 ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac, mentioned under “Ventricular arrhythmias: medical therapy and ablation”

Task Force on Sudden Cardiac Death of the European Society of Cardiology.
Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L, Breithardt G, Brugada P, Camm AJ, Cappato R, Cobbe SM, Di Mario C, Maron BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M, Vardas P, Wellens HJ, Zipes DP.
Eur Heart J 2001;22:1374-1450.

Update of the guidelines on sudden cardiac death of the European Society of Cardiology.
Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L, Breithardt G, Brugada P, Camm JA, Cappato R, Cobbe SM, Di Mario C, Maron BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M, Vardas P, Wellens HJ, Zipes DP.
Eur Heart J 2003;24:13-15.
Extensive ESC Task Force document on the epidemiology, etiology, primary and secondary prophylaxis, and different underlying cardiovascular pathology underlying sudden cardiac death. The guidelines were updated in a 2003 document.

Recent primary prevention implantable cardioverter defibrillator trials.
Duray G, Israel CW, Hohnloser SH.
Curr Opin Cardiol 2006;21:15-19.
Synopsis of clinical trials addressing the use of implantable cardioverter defibrillators in primary prevention of sudden death in patients with ischemic and non-ischemic cardiomyopathy or with a recent myocardial infarction.

ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines).
Gregoratos G, Abrams J, Epstein AE, Freedman RA, Hayes DL, Hlatky MA, Kerber RE, Naccarelli GV, Schoenfeld MH, Silka MJ, Winters SL, Gibbons RJ, Antman EM, Alpert JS, Gregoratos G, Hiratzka LF, Faxon DP, Jacobs AK, Fuster V, Smith SC, Jr.
Circulation 2002;106:2145-2161.
Update of the original 1998 guidelines for ICD implantation. These guidelines only include the findings from the first large primary prevention trial (MADIT-II).

A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators.
N Engl J Med 1997;337:1576-1583.
The AVID-trial is the largest secondary prevention trial in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia. It showed significant reductions in mortality.

Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone.
Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B.
Circulation 2000;101:1297-1302.

The CIDS trial was a secondary prevention trial in 659 patients after resuscitated VF or VT or with unmonitored syncope, randomly assigned to treatment with an ICD or with amiodarone. It showed a 20% relative risk reduction with ICD therapy in all-cause mortality and a 33% reduction in arrhythmic mortality compared with amiodarone but these reductions did not reach statistical significance

Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH).
Kuck KH, Cappato R, Siebels J, Ruppel R.
Circulation 2000;102:748-754.

The CASH-trial was the third secondary prevention trial that showed that ICD therapy in cardiac arrest survivors is associated with a 23% (albeit nonsignificant) reduction of all-cause mortality rates when compared with treatment with amiodarone or metoprolol. Of note, an initial propafenone arm of the study was prematurely discontinued after an interim analysis showed a 61% higher all-cause mortality rate than in ICD patients.

Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.

Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M.
N Engl J Med 1996;335:1933-1940.

Original MADIT-trial. Although a small trial (196 post-MI patients with an LVEF of ≤35%) it opened the era of prophylactic ICD implantations to protect patients without prior sudden death or sustained VT against sudden death. It concluded that in patients with a prior MI who are at high risk for ventricular tachyarrhythmia, prophylactic ICD therapy leads to improved survival as compared with conventional medical therapy.

A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G.
N Engl J Med 1999;341:1882-1890.

MUSTT was another primary prevention trial that evaluated whether electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. It concluded that electrophysiologically guided antiarrhythmic therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease.

Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.
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.
N Engl J Med 2005;352:225-237.

The SCD-HeFT trial randomized 2521 patients with NYHA class II or III, CHF and a LVEF of ≤35% to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy with a VVI-ICD. It concluded that amiodarone had no favorable effect on survival, whereas ICD therapy significantly reduced overall mortality by 23%

Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction.
Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ.
N Engl J Med 2004;351:2481-2488.

The DINAMIT trial showed that prophylactic ICD therapy 6 to 40 days after a myocardial infarction in patients with an LVEF of ≤35% and depressed heart-rate variability or an elevated average 24-hour heart rate, did not reduce overall mortality. Although ICD therapy was associated with a reduction in the rate of death due to arrhythmia, that was offset by an increase in the rate of death from nonarrhythmic causes

Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.
Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML.
N Engl J Med 2002;346:877-883.
Being the first large primary prevention trial, MADIT-II showed in 1232 patients with a prior myocardial infarction and a LVEF of ≤30% prophylactic implantation of a defibrillator significantly improved survival.

Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.
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.
N Engl J Med 2004;350:2151-2158.

The moderately sized DEFINITE trial, which randomized 458 patients with nonischemic dilated cardiomyopathy and a LVEF of ≤35% (and frequent VPB or nonsustained VT) to medical therapy alone or with the addition of a VVI-ICD, just failed to reach statistical significance to show a reduction in the risk of death from any cause.

Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease.
Wathen MS, Sweeney MO, DeGroot PJ, Stark AJ, Koehler JL, Chisner MB, Machado C, Adkisson WO.
Circulation 2001;104:796-801.

Prospective, multicenter study evaluating the efficacy of empirical antitachypacing (ATP) to terminate fast VT (FVT; >188 bpm) in 220 patients with coronary artery disease receiving an ICD for standard indications. It demonstrated that ATP can terminate 3 of 4 of these episodes with a low incidence of acceleration and syncope. ATP may safely reduce the morbidity of painful shocks.

Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy.
Maron BJ, Shen WK, Link MS, Epstein AE, Almquist AK, Daubert JP, Bardy GH, Favale S, Rea RF, Boriani G, Estes NA, 3rd, Spirito P.
N Engl J Med 2000;342:365-373.

Observational retrospective study on the benefit of ICDs in 128 patients with hypertrophic cardiomyopathy. After an average follow-up period of 3.1 y. ICDs were activated appropriately in 29 patients (23 percent), i.e. a rate of appropriate defibrillator discharge of 7 percent per year (11% in secondary prevention, 5% in prophylactic implants). A total of 32 patients (25 percent) had episodes of inappropriate discharges. The study indicates that ICDs have a role in the primary and secondary prevention of sudden death in selected high-risk patients with HCM.

Cost-effectiveness of implantable cardioverter-defibrillators.
Sanders GD, Hlatky MA, Owens DK.
N Engl J Med 2005;353:1471-1480.
Based on the data of all major recent primary prevention trials, the cost-effectiveness of ICD therapy was calculated. Compared with control therapy it ranged from 34,000 dollars to 70,200 dollars per QALY gained. Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years.

Cost-effectiveness of the implantable cardioverter-defibrillator versus antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias: results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic analysis substudy.
Larsen G, Hallstrom A, McAnulty J, Pinski S, Olarte A, Sullivan S, Brodsky M, Powell J, Marchant C, Jennings C, Akiyama T.
Circulation 2002;105:2049-2057.

Cost-effectiveness (C/E) calculations based on prospectively collected data of the patients in the AVID trial, the first randomised secondary prevention trial. The base-case C/E ratio was $66 677 per year of life saved by the ICD compared with AAD therapy (95% CI, $30 761 to $154 768). Six- and 20-year C/E ratios remained stable between $68 000 and $80 000 per year of life saved. The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias.

Addendum to "Personal and Public Safety Issues Related to Arrhythmias That May Affect Consciousness: Implications for Regulation and Physician Recommendations: A Medical/ Scientific Statement From the American Heart Association and the North American Society of Pacing and Electrophysiology." Public Safety Issues in Patients With Implantable Defibrillators. A Scientific Statement From the American Heart Association and the Heart Rhythm Society.
Epstein AE, Baessler CA, Curtis AB, Estes NA 3rd, Gersh BJ, Grubb B, Mitchell LB
Circulation 2007;115:1170-1176.

Extension of the original recommendations concerning driving with ICD from 1996, in which driving for patients with ICDs implanted for primary prevention was briefly discussed. It is now recommended that they should be restricted from driving a private automobile for at least 1 week to allow for recovery from implantation of the defibrillator. Thereafter, these driving privileges should not be restricted in the absence of symptoms potentially related to an arrhythmia. If they subsequently receive an appropriate therapy, especially with symptoms of cerebral hypoperfusion, they should be considered to be subject to the driving guidelines previously published for patients who received an ICD for secondary prevention.

Sudden cardiac arrest associated with early repolarization.
Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquie JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O'Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Clementy J.
N Engl J Med 2008;358:2016-2023.

This multicenter report describing 206 case subjects at 22 centers describes for the first time the association between a new QRS-ST junction variant and malignant ventricular arrhythmias. The variant was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The variant was significantly more frequent in case subjects with idiopathic VF than in 406 matched control subjects (31% vs. 5%, P<0.001). Cases were more often male and and had a history of syncope or sudden cardiac arrest during sleep. Moreover, ICD patients with a repolarization abnormality more often had recurrent VF than those without such an abnormality (HR 2.1; P=0.008).

Quality of life with defibrillator therapy or amiodarone in heart failure.
Mark DB, Anstrom KJ, Sun JL, Clapp-Channing NE, Tsiatis AA, Davidson-Ray L, Lee KL, Bardy GH.
N Engl J Med 2008;359:999-1008.

Of particular importance in health-economic evaluations of ICD therapy is whether ICD treatment is accompanied by deterioration in the quality of life (QOL) is unclear. QOL was prospectively measured in 2521 SCD-HeFT patients at months 3, 12, and 30. Psychological well-being in the ICD group, as compared with medical therapy alone, was significantly improved at 3 months (P=0.01) and at 12 months (P=0.003) but not at 30 months. No clinically or statistically significant differences in physical functioning among the study groups were observed. ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains. The use of amiodarone had no significant effects on the primary quality-of-life outcomes. Therefore, the authors conclude that single-lead ICD therapy was not associated with any detectable adverse quality-of-life effects during 30 months of follow-up.