Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods.

BACKGROUND

In medically-treated patients with ischemic cardiomyopathy, myocardial viability is associated with a worse prognosis than scar. The risk is especially great with hibernating myocardium (chronic regional dysfunction with reduced resting flow), and the excess mortality appears to be due to sudden cardiac death (SCD). Hibernating myocardium also results in sympathetic nerve dysfunction, which has been independently associated with risk of SCD.

OBJECTIVES

PAREPET is a prospective, observational cohort study funded by NHLBI. It is designed to determine whether hibernating myocardium and/or inhomogeneity of sympathetic innervation by positron emission tomography imaging identifies patients with ischemic cardiomyopathy who are at high risk for SCD and cardiovascular mortality.

METHODS

Patients with documented ischemic cardiomyopathy, an ejection fraction of <or=35%, and with no plans for coronary revascularization will be recruited. Major exclusion criteria include: history of resuscitated SCD, sustained VT, ICD discharge, or unexplained syncope; recent myocardial infarction (30 days), percutaneous coronary intervention (3 months), coronary bypass surgery (1 year); or comorbidities that would be expected to reduce life expectancy to <2 years. All patients will undergo transthoracic echocardiography, and dynamic cardiac positron emission tomography to quantify resting perfusion (13N-ammonia), norepinephrine uptake as an index of sympathetic innervation (11C-meta-hydroxyephedrine), and metabolic viability (18F-2-deoxyglucose during glucose-insulin clamp). The development of SCD or cardiovascular mortality will be determined by telephone follow-up every three months. In patients with an implantable cardiac defibrillator, appropriate device discharge will be considered a surrogate for SCD.

CONCLUSION

The PAREPET study will prospectively determine whether the amount of viable dysfunction myocardium and/or cardiac sympathetic dysinnervation is associated with the risk of SCD. It is anticipated that the results of this trial will more specifically identify myocardial substrates of SCD. This will help target therapies intended to reduce arrhythmic death to those patients with the greatest likelihood of benefit.