Sudden cardiac death continues to be a major contributor to mortality in patients with ischemic cardiomyopathy. While implantable defibrillators can prevent death from ventricular arrhythmias, our current approach to identify patients at highest risk primarily rests on demonstrating a reduction in left ventricular ejection fraction less than 35%. The purpose of this observational cohort study is to prospectively test whether this can be enhanced by quantifying the amount of sympathetic denervation, left ventricular end-diastolic volume or brain natriuretic peptide levels.

Using current guidelines based primarily on ejection fraction (EF), only one-quarter of patients receiving an implantable cardiac defibrillator (ICD) for the primary prevention of sudden cardiac arrest (SCA) require appropriate ICD therapy within 5 years. The NIH-sponsored PAREPET study (Prediction of ARrhythmic Events with Positron Emission Tomography, ClinicalTrials.gov, NCT01400334) identified four independent risk factors that predict SCA or ICD equivalent in patients with ischemic cardiomyopathy. Using retrospectively defined cut-points, the absence of these risk factors identified 38% of the cohort with a very low risk of SCA (<1% per year). This rate is actually lower than the 1.5-2% annual rate of SCA among patients with coronary artery disease and mild left ventricular (LV) dysfunction, who are not considered candidates for a primary prevention ICD. This proposal will prospectively determine whether these risk factors can form the basis of a clinically applicable approach to identify a subgroup of patients who are candidates for an ICD, but are at low enough risk of SCA to have an ICD safely withheld. Our long-term goal is to develop better approaches to identify patients with coronary artery disease who are most likely to benefit from prevention of SCA with placement of an implantable defibrillator.

Inclusion Criteria:

• Coronary artery disease (by cardiac catheterization or definite myocardial infarction)

• ICD implantation for the primary prevention of SCA

• Primary prevention patients with a Biventricular ICD

  • Eligible immediately when this is placed to prevent dysynchrony related to intermittent RV pacing and the native QRS duration is ≤ 130 msec in the absence of pacing.
  • Eligible 6 months after implantation when the native QRS duration prior to implant is >130 msec or there is persistent RV pacing.

• Optimal medical therapy for heart failure.

Exclusion Criteria:

• Plans for coronary revascularization (due to the independent impact on SCA)
• Contraindication for PET (i.e. claustrophobia, pregnancy, physical limitation)
• Tricyclic antidepressant use (inhibits norepinephrine and LMI1195 uptake)
• Comorbidities limiting life expectancy <2yr.
• Age <18 years or inability to provide informed consent
• Primary prevention ICD/BiV recipients who have received an appropriate ICD shock prior to enrollment

The study population comprises adult patients of either sex with ischemic cardiomyopathy who have an ejection fraction ≤ 35% and New York Heart Association Class II or III CHF or an ejection fraction ≤ 30% and Class I CHF who are candidates to place an ICD for the primary prevention of SCA. Subjects already having a primary prevention ICD are eligible if they have not yet received an appropriate ICD shock for ventricular arrhythmias.