Analysis of mortality events in the multicenter automatic defibrillator implantation trial (MADIT-II)

Greenberg, Henry; Case, Robert B.; Moss, Arthur J.; Brown, Mary W.; Carroll, Emily; Andrews, Mark; Investigators, Madit-Ii

doi:10.1016/j.jacc.2003.11.038

Cited by 322 publications

(236 citation statements)

References 9 publications

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“…Ventricular tachyarrhythmias account for ≈50% of deaths in patients with chronic MI and ischemic HF 28. Since many conventional therapies for HF‐related arrhythmias that target sarcolemmal ion channels are fraught with pro‐arrhythmic effects, there is a major unmet need for developing novel approaches that are both effective and safe.…”

Section: Discussionmentioning

confidence: 99%

Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction

Motloch

Cacheux

Ishikawa

et al. 2018

JAHA

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Background SERCA2a gene transfer (GT) improves mechano‐electrical function in animal models of nonischemic heart failure Whether SERCA2a GT reverses pre‐established remodeling at an advanced stage of ischemic heart failure is unclear. We sought to uncover the electrophysiological effects of adeno‐associated virus serotype 1.SERCA2a GT following myocardial infarction (MI).Methods and ResultsPigs developed mechanical dysfunction 1 month after anterior MI, at which point they received intracoronary adeno‐associated virus serotype 1.SERCA2a (MI+SERCA2a) or saline (MI) and were maintained for 2 months. Age‐matched naive pigs served as controls (Control). In vivo ECG‐and‐hemodynamic properties were assessed before and after dobutamine stress. The electrophysiological substrate was measured using optical action potential (AP) mapping in controls, MI, and MI+SERCA2a preparations. In vivo ECG measurements revealed comparable QT durations between groups. In contrast, prolonged QRS duration and increased frequency of R′ waves were present in MI but not MI+SERCA2a pigs relative to controls. SERCA2a GT reduced in in vivo arrhythmias in response to dobutamine. Ex vivo preparations from MI but not MI+SERCA2a or control pigs were prone to pacing‐induced ventricular tachycardia and fibrillation. Underlying these arrhythmias was pronounced conduction velocity slowing in MI versus MI+SERCA2a at elevated rates leading to ventricular tachycardia and fibrillation. Reduced susceptibility to ventricular tachycardia and fibrillation in MI+SERCA2a pigs was not related to hemodynamic function, contractile reserve, fibrosis, or the expression of Cx43 and Nav1.5. Rather, SERCA2a GT decreased phosphoactive CAMKII‐delta levels by >50%, leading to improved excitability at fast rates.Conclusions SERCA2a GT increases conduction velocity reserve, likely by preventing CAMKII overactivation. Our findings suggest a primary effect of SERCA2a GT on myocardial excitability, independent of altered mechanical function.

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Section: Discussionmentioning

confidence: 99%

Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction

Motloch

Cacheux

Ishikawa

et al. 2018

JAHA

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“…7 This committee determined, to the extent possible, the cause of death (cardiac or noncardiac) and the mode of cardiac death (sudden or nonsudden). 6 …”

Section: Follow-up and End Pointsmentioning

confidence: 99%

“…[1][2][3][4][5] The lifesaving benefit achieved with the ICD is due to a reduction in sudden cardiac death. 6 In the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II), all the implanted devices had the capability for antitachycardia pacing to terminate reentrant ventricular tachycardia (VT) with appropriately timed pacemaker stimuli and the ability to deliver an internal shock for termination of fast VT or ventricular fibrillation (VF). The implanted devices also stored records of all therapy delivered by the ICD, and this information was routinely retrieved by device interrogation at regular follow-up visits during the course of the study.…”

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confidence: 99%

Long-Term Clinical Course of Patients After Termination of Ventricular Tachyarrhythmia by an Implanted Defibrillator

et al. 2004

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Background-The implanted cardioverter defibrillator (ICD) improves survival in high-risk cardiac patients. This analysis from the MADIT-II trial database examines the long-term clinical course and subsequent mortality risk of patients after termination of life-threatening ventricular tachyarrhythmias by an ICD. Methods and Results-Life-table survival analysis was performed, and proportional hazards regression analysis was used to evaluate the contribution of baseline clinical factors and time-dependent defibrillator therapy to mortality during long-term follow-up. Of 720 patients with an ICD (average follow-up 21 months), 169 patients received 701 antiarrhythmic device therapies for ventricular tachyarrhythmias. Few baseline characteristics distinguished patients who received appropriate ICD therapy for their first ventricular tachyarrhythmic episode. The probability of survival for at least 1 year after first therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) was 80%. The hazard ratios for the risk of death due to any cause in those who survived appropriate therapy for termination of VT and VF were 3.4 (PϽ0.001) and 3.3 (Pϭ0.01), respectively, compared with those who survived without receiving ICD therapy, with a high frequency of heart failure and late nonsudden cardiac death after first successful ICD therapy for VF. Conclusions-Successful appropriate therapy by an ICD for VT or VF is associated with 80% survival at 1 year after arrhythmia termination. These patients are at increased risk for heart failure and nonsudden cardiac death after device termination of VT or VF and should receive special attention for the prevention and management of progressive left ventricular dysfunction during long-term follow-up.

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“…The ICD therapy resulted in a 31% reduction in the risk of all-cause mortality and a 67% reduction in sudden cardiac death. 53) There are two large primary prevention trials that did not demonstrate ICD benefit in reducing mortality, The CABG Patch Trial 54) and Defibrillator in Acute Myocardial Infarction Trial (DINAMIT). 55) The CABG Patch Trial enrolled 900 patients, mean age of 63 years, to evaluate whether ICDs implanted at the time of CABG reduced mortality in patients with EF of 35% or less and an abnormal signalaveraged ECG.…”

Section: Device-based Therapymentioning

confidence: 99%

Ventricular Arrhythmias in the Elderly

Minor

Akiyama

2006

Journal of Arrhythmia

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The management of malignant ventricular arrhythmias will become gradually more important as life expectancy continues to increase. The incidence of sudden cardiac death and overall cardiac mortality is more pronounced in the elderly mainly as a reflection of the higher prevalence of ischemic heart disease. With the exception of beta‐blocker therapy, antiarrhythmic drug therapy has not proven to be effective in the prevention of sudden cardiac death. Implantable cardioverter‐defibrillator therapy has been shown to reduce both overall mortality and arrhythmic death when following current guidelines for implantation and appears to be applicable to any age group when sensible patient selection is implemented. The greater efficacy of this therapy relative to antiarrhythmic therapies supports its expanded use in the elderly population. Such therapy has a similar cost‐effectiveness to other accepted interventions and does not appear to be associated with reduced quality of life or age‐specific complications. The clinical approach to elderly patients at risk of sudden death from ventricular arrhythmias will continue to evolve as new technologies are developed, but the future of ventricular arrhythmia treatment in the elderly will likely emphasize an increasing utilization of both implantable cardioverter‐defibrillator and beta‐blocker therapies.

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Analysis of mortality events in the multicenter automatic defibrillator implantation trial (MADIT-II)

Abstract: The decrease in mortality with ICD therapy in MADIT-II is entirely due to a reduction in SCD, with similar reductions in SCD in a spectrum of subgroups stratified according to relevant baseline characteristics.

Cited by 322 publications

References 9 publications

Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction

Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction

Long-Term Clinical Course of Patients After Termination of Ventricular Tachyarrhythmia by an Implanted Defibrillator

Ventricular Arrhythmias in the Elderly

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