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Introduction: FDA approved external counterpulsation (ECP) improves coronary collateral flow index measured invasively, using intracoronary wedge pressure beyond a severe stenosis. However, there is presently no noninvasive method to measure coronary collateral flow capacity (CCFC), in patients with total coronary occlusion (CTO). Hypothesis: CCFC can be measured noninvasively by comparing the improvement in flow in the ischemic bed beyond CTO, using dobutamine stress (DBT), which supports supply side pressure, compared with vasodilator stress (DIP), which lowers supply side pressure, causing coronary steal. Methods: Seven patients with CTO were treated with 35 sessions of ECP, and studied with both DIP and DOB stress PET myocardial perfusion imaging. Coronary flow capacity (CFC), which integrates absolute rest and stress flow with coronary flow reserve on a per pixel basis, was measured objectively with FDA approved HeartSee software. Results: As shown in the Table, all patients demonstrated a decrease in the size of the ischemic zone at risk, defined as moderate or severely reduced CFC, when CFC with DIP was compared with DOB: 28% LV mass vs. 5%; p &lt 0.01. Five of 7 patients also demonstrated significant improvement in global CFC by Kolmogorov-Smirnoff analysis. Absolute stress flow into the ischemic zone improved significantly in all ECP treated patients during demand ischemia compared with vasodilator stress (1.9 vs. 1 ml/min/g; p &lt 0.01). One of the two patients who did not improve global CFC, despite ECP treatment, underwent coronary arteriography demonstrating a new flow limiting stenosis in the supply side vessel, which was successfully stented. Conclusion: ECP treatment is associated with improved coronary collateralization in patients with CTO, which can be identified noninvasively with quantitative PET myocardial perfusion imaging.

Objectives This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients. Background There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience. Methods A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028). Results Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively. Conclusions A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols.

A drop in blood pressure (BP) or blunted BP response is an established high-risk marker during exercise myocardial perfusion imaging (MPI); however, data are sparse regarding the prognostic value of BP response in patients undergoing vasodilator stress rubidium-82 (Rb-82) Positron Emission Tomography (PET) MPI. From the PET Prognosis Multicenter Registry, a cohort of 3413 patients underwent vasodilator stress Rb-82 PET MPI with dipyridamole or adenosine. We used multivariable Cox proportional hazard regression to analyze the association with mortality of four BP variables: stress minus rest systolic BP (∆SBP), stress minus rest diastolic BP (∆DBP), resting systolic BP (rSBP), and resting diastolic BP (rDBP). Covariates that had univariate P values

Background: Heart disease continues to be the leading cause of death, and the prevalence of coronary artery disease is expected to increase as the population ages. It is important to understand the clinical utility of medical tests, or its lack thereof, in the aging population. The objective of this study was to understand the incremental prognostic value of positron emission tomographic (PET) myocardial perfusion imaging in the elderly (≥85 years of age). Methods and Results: A total of 3343 patients enrolled in a multicenter observational PET registry were analyzed. Participants were initially divided into 3 age categories: 65 to 74.9, 75 to 84.9, and ≥85 years of age and followed for all-cause death. Median follow-up time was 3 years. Of the total patient population, 248 patients (49% men) were ≥85 years old. When compared with younger patients, individuals ≥85 years had a higher prevalence of hypertension (79%) and a lower incidence of dyslipidemia (54%) and diabetes mellitus (24%). On multivariable analysis, %left ventricular stress defect and %left ventricular ischemia were predictors of patient outcome for those Conclusions: The elderly is a high-risk population irrespective of PET myocardial perfusion imaging results, and incremental prognostic value of PET myocardial perfusion imaging appears to wane in those ≥85 years of age. Although PET myocardial perfusion imaging may be diagnostically useful in the elderly, its prognostic value in this population requires further evaluation.

Serial myocardial perfusion imaging (MPI) is valuable for assessing coronary disease progression and treatment efficacy. Previous serial MPI studies emphasized severe perfusion defects, with no attention given to milder perfusion defects. Thus, this study sought to compare and identify predictors of change in severe versus mild perfusion defect size in patients who underwent serial positron emission tomography (PET) MPI. Serial PET MPI was performed in 551 patients with an average of 1.9 years between scans. Severe and mild perfusion defect size at both PETs were derived from automated software as percentage of left ventricular mass with relative tracer activity60% (severe) and between 61% and 80% of maximum tracer activity (mild), respectively. Predictors of change in severe and mild perfusion defect size between PETs were determined. Overall, severe perfusion defect sizes improved (p0.001) and mild perfusion defect sizes worsened (p0.001) between PETs with individual changes being highly variable. In individuals with negligible changes in severe defect size (±2%), changes in mild defect size ranged from a worsening of 47% to an improvement of 48% of left ventricular mass. The strongest predictors of change in severe defect size were indicators of obstructive coronary disease including interval myocardial infarction, interval revascularization, history of myocardial infarction, and history of bypass surgery. Strong predictors of change in mild defect size were cardiac risk factors including male gender, body mass index, diabetes, and smoking. In conclusion, changes in mild perfusion defects may provide valuable secondary information for evaluating treatment efficacy in patients who underwent serial MPI.

Objectives The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET). Background The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established. Methods A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated. Results The 5-year CAD mortality was 3.7% for women and 6.0% for men (p Conclusions Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Objectives: The primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classifica...

Background: Myocardial perfusion imaging by positron-emission tomography (PET MPI) is regarded as a valid technique for the diagnosis of coronary artery disease (CAD), but the incremental prognostic value of PET MPI among individuals with known or suspected CAD is not firmly established. Hypothesis: Myocardial perfusion defect sizes as measured by PET MPI using automated software will provide incremental prognostic value for cardiac and all-cause mortality. Methods: This study included 3739 individuals who underwent rest-stress rubidium-82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress-induced myocardial perfusion defect sizes were determined objectively by automated computer software. Study participants were followed for a mean of 5.2 years for cardiac and all-cause mortality. Cox proportional hazards models were developed to evaluate the incremental prognostic value of PET MPI. Results: A strong correlation was observed between perfusion defect sizes assessed visually and by automated software (r = 0.76). After adjusting for cardiac risk factors, known CAD, noncoronary vascular disease, and use of cardioprotective medications, stress perfusion defect size was strongly associated with cardiac death (P < 0.001). Rest perfusion defects demonstrated a stronger association with cardiac death (P < 0.001) than stress-induced perfusion defects (P = 0.01), yet both were highly significant. Similar patterns held for all-cause death. Conclusions: The current study is the largest to date demonstrating PET MPI provides incremental prognostic value among individuals with known or suspected CAD. Automated calculation of perfusion defect sizes may provide valuable supplementary information to visual assessment. This work was partially funded by a predoctoral fellowship grant awarded to the first author by the American Heart Association's Founders' Affiliate. Additional funding was provided by Niagara Falls Memorial Medical Center, Positron Corporation, the University at Buffalo, and Niagara University. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Aims We sought to determine the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with prior coronary artery bypass graft (CABG) surgery. PET MPI has recently been shown to provide incremental risk stratification for patients with suspected coronary artery disease (CAD), but the prognostic utility of PET MPI in CABG patients has not been well studied. Methods and results A multi-centre PET registry of 7061 patients who underwent Rb-82 PET MPI from four participating centres was screened. Nine hundred and fifty-three CABG patients were identified and their images were analysed. Outcomes of all-cause mortality and cardiac death were collected. With a mean follow-up of 2.4 ± 1.4 years, 128 (13.4%) all-cause deaths and 44 (4.6%) cardiac deaths were observed. Multivariable analyses, adjusted for clinical variables, demonstrated that the summed stress score (SSS) was a significant independent predictor of both all-cause mortality [HR: 1.60 (per 1 category increase in SSS); 95% CI: 1.34–1.92; P < 0.001] and cardiac death (HR: 1.80; 95% CI: 1.33, 2.44; P < 0.001). The receiver-operator characteristic (ROC) curves showed that the addition of SSS increased the area under the curve (AUC) from 0.645 to 0.693 ( P = 0.014) for all-cause mortality, and from 0.612 to 0.704 ( P = 0.027) for cardiac death. SSS also improved the net reclassification improvement (NRI) for all-cause mortality (category-free NRI = 0.422; 95% CI: 0.240–0.603; P < 0.001) and cardiac death (category-free NRI = 0.552; 95% CI: 0.268–0.836; P < 0.001). Conclusions PET MPI provides independent and incremental prognostic value to clinical variables in predicting all-cause mortality and cardiac death in CABG patients.

An impaired chronotropic response to exercise is an accepted risk marker but the relationship between heart rate reserve (HRR) with pharmacologic stress is less well-established. The primary aim of this analysis was to evaluate the prognostic significance of HRR in patients undergoing rest/stress myocardial perfusion positron emission tomography (PET) in estimating coronary artery disease (CAD) mortality. This subset analysis from the PET Prognosis Multicenter Registry includes a total of 2,398 patients undergoing rest/stress Rb-PET from three participating sites. The HRR from rest to peak stress was categorized into tertiles of ≤4, 5-14, and ≥15 beats per minute (bpm). At stress, the % abnormal myocardium was categorized as

Objectives As accumulation of monocytes and macrophages is a feature of atherosclerotic plaque at all stages, inflammatory gene expression profiling of peripheral blood mononuclear cells may provide a more reliable measure of atherogenesis than systemic inflammatory markers. The aim of this study was to determine whether expression patterns of inflammatory regulators in blood are correlated with severity and progression of coronary artery disease. Methods PCR expression arrays were used to profile mRNA levels of 84 candidate genes in blood from three patients with persistent perfusion defects, three with improved perfusion, and two without perfusion defects as measured by serial PET myocardial perfusion imaging. A case-control study compared expression of inflammatory genes in 25 patients with stress-induced perfusion defects and 25 controls using quantitative real-time PCR. Results Expression array analysis identified IL-8, CXCR1, and CXCR2 as genes showing increased expression in patients with persistent perfusion defects. The case-control study confirmed a significant increase in CXCR1 (P=0.04) and CXCR2 (P=0.002) mRNAs in blood in males with obstructive CAD, but not in females. There was no difference in IL-8 mRNA level between cases and controls (P=0.1). Coordinated expression of CXCR1 and CXCR2 mRNA was more pronounced in controls (r=0.96) than in patients with perfusion defects (r=0.73). Conclusions mRNA levels for CXCR1 and CXCR2 are increased in blood in males with obstructive CAD and decreased in patients with improved perfusion, suggesting that these genes may serve as markers of disease severity and progression.

A drop in blood pressure (BP) or blunted BP response is an established high-risk marker during exercise myocardial perfusion imaging (MPI); however, data are sparse regarding the prognostic value of resting BP and BP response in patients undergoing vasodilator stress Rubidium-82 (Rb-82) Positron

Background: PET myocardial perfusion imaging (PET MPI) identifies coronary disease (CAD) progression and reversal in response to lipid lowering therapy (LLT), however, the optimal lipid values necessary to reverse CAD are unknown. In practice, NCEP ATP III guidelines (NCEP) are used as clinical targets. The purpose of this study was to evaluate the efficacy of aggressive LLT, beyond NCEP guidelines, to induce arrest or reversal of CAD as assessed with PET MPI. Methods: 147 patients with iv dipyridamole stress induced myocardial perfusion defects at baseline, treated for 1.5 years to beyond NCEP guidelines, underwent follow-up PET MPI and outcome assessment for MI, coronary death, CABG, CVA, and PTCI. Paired stress PET MPI studies were analyzed with automated software to determine the average uptake of 82-Rb in the anterior, septal, inferior, lateral and apical segments, normalized to peak myocardial activity. Baseline and follow-up MPI studies were then compared with the paired t-test, to identify significant improvement, worsening, or stabilization in segmental perfusion in each patient. Results: With LLT: 24 patients demonstrated improvement in myocardial perfusion, 96 patients no change, and 27 progression of CAD despite LLT. At mean follow-up of 15 months after the second PET study, coronary events occurred in 4.2%, 4.2%, and 22.2% respectively. Conclusions: PET MPI identifies 18% of patients with progressive CAD despite successful LLT which exceeds NCEP guidelines. These patients with progressive CAD identified by PET, have a significant (five fold ) increased risk of subsequent hard coronary events, compared with those patients demonstrating CAD arrest or reversal. Baseline Follow Up % Change p-value Total Cholesterol 169 +/− 38 152 +/− 30 −10.1 0.0001 LDL 96 +/− 35 84 +/− 23 −12.5 0.001 HDL 45 +/− 13 49 +/− 14 8.9 0.01 Triglyceride 136 +/− 73 106 +/− 60 −22.1 0.0001

To assess the accuracy of positron emission tomography (PET) for evaluation of coronary artery disease (CAD), cardiac PET perfusion images were obtained at rest and with dipyridamole-handgrip stress in 193 patients undergoing coronary arteriography. PET images were reviewed by two independent readers blinded to clinical data. Subjective defect severity scores were assigned to each myocardial region on a 0 (normal) to 5 (severe) scale. Results were compared with arteriographic stenosis severity expressed as stenosis flow reserve (SFR), with continuous values ranging from 0 (total occlusion) to 5 (normal), calculated from quantitative arteriographic dimensions using automated detection of the vessel borders. There were 115 patients with significant CAD (SFR less than 3), 37 patients with mild CAD (3 less than or equal to SFR less than 4), and 41 patients with essentially normal coronaries (SFR greater than or equal to 4). With increasingly severe impairment of stenosis flow reserve, subjective PET defect severity increased. Despite wide scatter, a PET score of 2 or more was highly predictive of significant flow reserve impairment (SFR less than 3). For each patient, the score of the most severe PET defect correlated with the SFR of that patient's most severe stenosis (rs = 0.77 +/- 0.06). For each of 243 stenoses, PET defect score correlated with the SFR of the corresponding artery (rs = 0.63 +/- 0.08). PET defect location closely matched the region supplied by the diseased artery, and readers agreed whether the most severe PET defect was less than or more than 2 for 89% of patients.

ObjectivesThis study sought to determine and compare the prognostic and incremental value of positron emission tomography (PET) in normal, overweight, and obese patients.BackgroundCardiac rubidium 82 (Rb-82) PET is increasingly being used for myocardial perfusion imaging (MPI). A strength of PET is its accurate attenuation correction, thereby potentially improving its diagnostic accuracy in obese patients. The prognostic value of PET in obese patients has not been well studied.MethodsA total of 7,061 patients who had undergone Rb-82 PET MPI were entered into a multicenter observational registry. All patients underwent pharmacologic Rb-82 PET and were followed for cardiac death and all-cause mortality. Based on body mass index (BMI), patients were categorized as normal (

Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2-18F]-2-deoxyglucose (FDG) and 82Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition.