PET promising for identifying cardiac mismatch

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A multiple radiotracer investigational study conducted at the University of Washington in Seattle shows that PET technology may be efficacious in determining the potential for adverse outcomes in patients with congestive heart failure (CHF). Arrhythmogenic right ventricular dysplasia, which predisposes to fatal arrhythmias, has demonstrated a significant reduction of post-synaptic—adrenergic receptor (BAR) density and a lesser decrease in pre-synaptic function. The imbalance, or mismatch, may cause or exacerbate arrhythmias and is thought to increase the risk of sudden cardiac death.

A multidisciplinary team from the departments of cardiology and radiology at the institution, employing a cocktail of three radiotracers, utilized PET to image pre- and post-synaptic function, as well as myocardial blood flow (MBF) in a cohort of patients with ischemic CHF against a group of healthy age-matched volunteers.

“The purpose of this study was to determine the extent and magnitude of regional mismatch between pre- and postsynaptic function in patients with ischemic CHF in comparison with that of age-matched healthy subjects and to relate mismatch to adverse events during follow-up,” the authors wrote.

Their results, published last month in the Journal of Nuclear Medicine, indicate that mismatch between pre- and post-synaptic left ventricular (LV) sympathetic function is present in patients with severe CHF and may be more marked in those with adverse outcomes.
The scientists studied two populations: 13 male patients (mean age, 72) with coronary artery disease (CAD) and CHF from depressed LV function and 25 (13 female, 12 male) healthy volunteers, also with a mean age of 72.

“The healthy volunteers were screened to exclude current smoking, hypertension, chronic medication use, or any cardiovascular or pulmonary disease,” the authors stated. “All had unremarkable blood counts and chemistries, including cholesterol and thyroid-stimulating hormone, urinalysis, normal 2-dimensional and Doppler echocardiograms for age, and normal maximal post-exercise SPECT 99mTc-sestamibi images.”

The PET studies were conducted on a GE Healthcare Advance system and employed a three-radiotracer imaging protocol. Pre-synaptic function was measured by imaging uptake of 11Cmeta-hydroxyephedrine (11C-mHED), a norepinephrine (NE) analog. For post-synaptic function, BAR density was measured by imaging (S)-4-3’-t-butylamino-2’-hydroxypropoxy)-benzimidazol-2-11C-one (11C-CGP12177); MBF was measured by imaging 15O-water.

“When studying mismatch, and mismatch heterogeneity, it is advantageous to study the smallest possible coregistered regions of sequential images,” the authors wrote. “Our PET method approaches this goal.”

The researchers reported that the dynamic PET image sets were reconstructed, decay-corrected to the time of each radiotracer injection, reoriented into short-axis cardiac projections, and analyzed.

The mean and range of regional mismatch scores within each individual subject were compared in the healthy subjects and in subjects with and without adverse cardiac events, according to the researchers. In follow-up monitoring over a period of 18 months, they found no adverse events in the 25-member healthy subject group.

However, in the CAD/CHF population, they found that 3 of the 4 patients who experienced an adverse event during this period presented with mean mismatch score of greater than 6 above the standard deviation above the mean of the healthy subjects. In the CAD/CHF cohort overall, 43 percent who presented with a mean mismatch score greater than the upper limit of normal (2 times the standard deviation) had an adverse event.

Although the scientists noted that their procedure requires evaluation and confirmation in a much larger patient population before being considered in the clinical management of patients with CHF, they are encouraged by the results of the study.

“Our preliminary study suggests that patients with the greatest mismatch had more adverse events,” they wrote. “We also demonstrated that such PET can be done within a short time period that minimizes the potential for changes in sympathetic function, is clinically acceptable, and does not cause clinically significant hemodynamic changes in patients with moderately severe CHF.”