1169 Objectives SPECT RNA can be used to quantify wall motion, and has been investigated for its potential at predicting cardiac resynchronization therapy response (CRT). However, the quantitative analysis of wall-motion curves, which is currently qualitative in nature, may hold potential for other applications as well. However, before abnormal wall-motion can be assessed, normal wall motion must be quantified. In this work, intra-segment and inter-subject variation in wall-motion curves was assessed in a population with normal cardiac function. Methods Using an in-house developed SPECT RNA program, 8-gate wall-motion curves were obtained at 568 locations around the myocardium for each of 50 subjects with normal cardiac function (LVEF>55%, QRS Results Normalized time-activity curves were successfully produced for all 50 patients. Mean intra-segment variation was found to be 34% and the mean inter-subject variation was found to be 11% averaged over all gates. The greatest intra-segment variations occurred in the end-systolic gates. Conclusions Normal cardiac mean variations and time-activity curves were obtained. From this data, a normal database of wall-motion curves can be developed for use in assessing abnormal regions, which may have applications in the prediction of CRT response
1076 Objectives Chemokines receptors (CR) are involved in the process of inflammatory diseases. Radiolabeled CR antagonists can be used to image inflammation. Our goal is to develop an 123I labeled DAPTA peptide targeting CR CCR5, and to evaluate its potential as an inflammation imaging tracer using an atherosclerosis model. Methods DAPTA was radiolabeled with 123I using iodogen. Cold iodine compound was characterized by mass spectroscopy. Biodistribution was determined in C57BL/6 mice. Cell uptake studies were conducted in: a) primary spleen cells and HEK-293 cells; b) U87-CD4-CCR5 and U87-MG cells. The tracer was injected into: 1) 9 month old ApoE-/- mice with normal diet; 2) 4 month old ApoE-/- mice with high fat Western diet (HFD); 3) 4 month old C57BL/6 mice as controls. The mice were sacrificed at 2 hr p.i.. Aortas were dissected and autoradiography images were collected and compared with en face and Oil Red O images. The lesion uptake (%IDxkg/m2) in autoradiography images were quantified using standards. Results DAPTA was radiolabeled with 123I with high radiochemical purity (> 95%) and specific activity (980 mCi/µmol). The identification of the tracer was confirmed by HPLC and mass spectroscopy of the cold analog. Biodistribution showed high blood uptake, indicating slow clearance of the tracer. In vivo de-iodination resulted in high stomach and thyroid uptake.Cell uptake studies showed: i) the uptake in primary spleen cells was significantly higher than the negative control HEK-293 cells (ratio: 2.3 at 1 hr and 2.5 at 2 hr incubatio); ii) U87-CD4-CCR5 cells had ~ 1.4 fold higher uptake than the control U87-MG cells. Autoradiography showed that the lesion uptake of 4 month ApoE-/- HFD mice (0.561 ± 0.079%) was lower than the uptake of 9 month ApoE-/- mice (0.747 ± 0.073%), and ~1.6 fold higher than the control mice (0.343 ± 0.069%). Conclusions We have developed 123I-DAPTA targeting CCR5. The preliminary in vitro and ex vivo evaluation indicates its potential application as a SPECT tracer for imaging inflammation.
The impact of ablation of ganglionated plexuses (GPs) during ablation of atrial fibrillation (AF) on ventricular myocardial innervation is unknown. Previous animal studies have shown different electrophysiological outcomes of ventricular myocardial denervation after ablation of autonomic ganglia.1,2 A recent animal report demonstrated that the ligament of Marshall could represent a conduit between the left stellate ganglion and the ventricle.2 There have been no reports evaluating detailed GP mapping and ablation in the atria and potential effects on ventricular sympathetic myocardial innervation.
Abstract Aims This large prospective cohort study sought to confirm the incremental prognostic value of coronary computed tomographic angiography (CCTA) measured over a prolonged follow-up duration. CCTA has diagnostic and prognostic value but data supporting its long-term prognostic value in a large prospectively recruited cohort with suspected coronary artery disease (CAD) has been limited. Methods and results Consecutive patients (without history of myocardial infarction, revascularization, cardiac transplantation, and congenital heart disease) were prospectively enrolled. CCTA was evaluated for CAD severity, total plaque score (TPS), and left ventricular ejection fraction. Patients were followed for major adverse events (MAE) and major adverse cardiac events (MACE). Over a total of 99 months, 8667 consecutive CCTA patients (mean age = 57.1 ± 11.1 years, 52.9% men) were prospectively enrolled and followed for a mean duration of 7.0 ± 2.6 years. At follow-up, there were a total of 723 MAE, 278 MACE, 547 all-cause deaths, 110 cardiac deaths, and 104 non-fatal myocardial infarction. Patients without coronary atherosclerosis at the time of CCTA had a very low annual event rate for both MAE and MACE (0.45%/year and 0.19%/year, respectively). Both MAE and MACE increased with increasing TPS and severity of CAD. In patients with non-obstructive CAD and who were statin-naive, TPS ≥5 had MACE rates >0.75%/year. Patients with high-risk CAD had an annual MAE and MACE rates of 3.52%/year and 2.58%/year, respectively. Adjusted hazard ratio of the severity of CAD based on multivariable analyses indicated that the prognostic values were incremental. Conclusion CCTA has independent and incremental prognostic value that is durable over time. The absence of coronary atherosclerosis portends an excellent prognosis. Patients with increasing non-obstructive plaque burden have worse prognosis and a TPS threshold ≥5 may identify a population that may benefit from statin therapy.
Noninvasive quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) provides incremental benefit to relative myocardial perfusion imaging (MPI) to diagnose and manage heart disease. MBF can be measured with single-photon emission computed tomography (SPECT) but the uncertainty in the measured values is high. Standardization and optimization of protocols for SPECT MBF measurements will improve the consistency of this technique. One element of the processing protocol is the choice of kinetic model used to analyze the dynamic image series.This study evaluates if a net tracer retention model (RET) will provide a better fit to the acquired data and greater test-retest precision than a one-compartment model (1CM) for SPECT MBF, with (+MC) and without (-MC) manual motion correction.Data from previously acquired rest-stress MBF studies (31 SPECT-PET and 30 SPECT-SPECT) were reprocessed ± MC. Rate constants (K1) were extracted using 1CM and RET, +/-MC, and compared pairwise with standard PET MBF measurements using cross-validation to obtain calibration parameters for converting SPECT rate constants to MBF and to assess the goodness-of-fit of the calibration curves. Precision (coefficient of variation of test re-test relative differences, COV) of flow measurements was computed for 1CM and RET ± MC using data from the repeated SPECT MBF studies.Both the RET model and MC improved the goodness-of-fit of the SPECT MBF calibration curves to PET. All models produced minimal bias compared with PET (mean bias < 0.6%). The SPECT-SPECT MBF COV significantly improved from 34% (1CM+MC) to 28% (RET+MC, P = 0.008).The RET+MC model provides a better calibration of SPECT to PET and blood flow measurements with better precision than the 1CM, without loss of accuracy.
