DINAMIT

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Hohnloser SH, et al. "Prophylactic use of an implantable cardioverter–defibrillator after acute myocardial infarction". The New England Journal of Medicine. 2004. 351(24):2481-2488.
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Clinical Question

In patients with LV systolic dysfunction (LVEF ≤35%) and impaired autonomic function in the setting of acute MI, does early prophylactic ICD placement decrease mortality compared to medical therapy alone?

Bottom Line

Prophylactic implantation of an ICD 6-40 days after acute MI in patients with LV dysfunction (LVEF ≤ 35%) and impaired autonomic function reduces arrhythmic deaths but does not improve all-cause mortality.

Major Points

Two large RCTs (MADIT-II and SCD-HeFT) have established the use of ICDs as primary prophylaxis for patients with LVEF ≤35%. However, these trials were not designed to assess the role of ICD therapy in the immediate post-MI period when the risk of ventricular arrhythmia may be highest. In particular, previous studies have demonstrated that patients with markers of impaired autonomic function suffer from increased mortality,[1] suggesting that these patients are at especially high risk for sudden cardiac death.

Published in 2004, the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) randomized 674 patients with acute MI within the preceding 6-40 days, concomitant LV systolic dysfunction (LVEF ≤35%), and evidence of autonomic dysfunction (abnormal resting HR or reduced HR variability) to early prophylactic ICD placement versus optimal medical therapy (OMT) alone. DINAMIT demonstrated that at 30 months, early ICD placement did not reduce the risk of mortality (the study's primary outcome). There were fewer arrhythmic deaths in the ICD group, but this was offset by an increase in the rate of death from non-arrhythmic causes.

As a result of the DINAMIT trial, current ICD guidelines continue to recommend ICD therapy 40 days after MI rather than in the acute post-MI period.

Guidelines

AHA/ACCF Heart Failure (2013, adapted)[2]

  • ICD for patients with ischemic or non-ischemic CM ≥40 days post-MI in patients with LVEF ≤35% and NYHA class II or III symptoms on OMT with expected survival >1 year (class I, level A)
  • ICD for ICM ≥40 days post-MI with LVEF ≤30%, NYHA class I symptoms on OMT with expected survival >1 year (class I level B)

Design

  • Multicenter, randomized, open-label controlled trial.
  • N=674
    • ICD (n=332)
    • Control (n=342)
  • Setting: 73 sites in 12 countries
  • Enrollment: 1998-2003
  • Mean follow-up: 30 months
  • Analysis: Intention-to-treat
  • Primary outcome: All-cause mortality
  • Secondary outcome: Arrhythmic death

Population

Inclusion Criteria

  • Age 18-80 years
  • Recent MI in prior 6-40 days
  • LVEF ≤35%
  • Autonomic dysfunction (HR ≥80 or mean RR interval of ≤750 msec over a 24-hour period)

Exclusion Criteria

  • Acute HF or NYHA class IV at randomization
  • Non-cardiac, disease-limiting life expectancy
  • CABG performed since qualifying infarct or planned within 4 weeks of randomization.
  • 3-vessel PCI performed since qualifying infarct
  • Waiting list for cardiac transplant
  • Current and ongoing ICD therapy
  • Requirement for ICD (eg, sustained ventricular tachycardia)
  • Prior permanent pacemaker
  • Low probability that ICD could be implanted within 7 days of randomization.
  • Expected poor compliance with protocol

Baseline Characteristics

From the control group

  • Male: 77%
  • Age: 62 years
  • Prior MI: 33%
  • Prior CABG: 7%
  • Prior PTCA: 11%
  • DM2: 29%
  • HTN 45%
  • QRS duration: 105ms
  • HF with index MI: 49%
    • Class I 12%
    • Class II 59%
    • Class III 29%
  • Revascularization at index visit: 62%
  • LVEF: 28%
  • Beta blocker: 87%
  • ACE inhibitor: 94%
  • Antiplatelet: 92%
  • Lipid-lower agent: 80%

Interventions

  • Randomized in 1:1 fashion to receive single-chamber ICD or no ICD
  • Investigators encouraged to use OMT in all patients (ACE inhibitor, beta-blocker, aspirin, and statin as appropriate)
  • ICD implantation occurred within 1 week of randomization
  • Patients followed for a maximum of 4 years
  • Follow-up visits scheduled at 3 and 6 months post-randomization and every 6 months thereafter
  • All deaths adjudicated by a blinded central validation committee

Outcomes

Comparisons are ICD vs. control

Primary Outcomes

All cause mortality (%/yr)
7.5% vs. 6.9% (HR 1.08; 95% CI 0.76-1.55; P=0.66)

Secondary Outcomes

Arrhythmic death (%/yr)
1.5% vs. 3.5% (HR 0.42; 95% CI 0.22-0.83; P=0.009)
Non-arrhythmic cardiac death (%/yr)
4.1% vs. 2.4% (HR 1.72; 95% CI 0.99-2.99; P=0.05)
Non-cardiac vascular death (%/yr)
0.6% vs. 0.4% (HR 1.69; 95% CI 0.40-7.06; P=0.47)
Non-vascular Death
1.3% vs. 0.7% (HR 1.85; 95% CI 0.68-5.01; P=0.22)

Subgroup Analysis

A set of baseline clinical features was examined for potential subgroup effects and the effect of ICD remained consistent across all subgroups.

Adverse Events

Complications of ICD placement occurred in 25 patients; the most common of these were lead dislodgement, pneumothorax, and inappropriate shocks. There were no deaths related to device implantation.

Criticisms

  • Because of lower than expected mortality rates, the target enrollment was increased to 674 patients during the course of the study
  • Result may have been influenced by baseline imbalances including more amiodarone use and more PCI/CABG in the control group
  • Unblinded nature of the study may have allowed for effects of bias on study results (e.g., more control patients on amiodarone due to perceived lack of protection from arrythmia)
  • The study results cannot rule out a smaller (<25%) benefit of early ICD use on mortality in this population

Funding

  • Study funded by a grant from St. Jude Medical
  • Several authors either consult for or are employed by study sponsor

Further Reading

  1. La Rovere MT, et al. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 1998351;478-84.
  2. Yancy CW, et al. "2013 ACCF/AHA guideline for the management of heart failure." Circulation. 2013;128:e240-e327.