A Clinical Tool to Identify Candidates for Stress-First 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.

Is There an Age When Myocardial Perfusion Imaging May No Longer Be Prognostically Useful?

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 <85 years of age but was not statistically significant in those ≥85 years of age. The prognostic value of PET (%left ventricular stress defect and %left ventricular ischemia) appeared to decrease with advancing age. 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.

Prognostic value of vasodilator response using rubidium-82 positron emission tomography myocardial perfusion imaging in patients with coronary artery disease.

BACKGROUND: Prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) is well established. There is paucity of data on how the prognostic value of PET relates to the hemodynamic response to vasodilator stress. We hypothesize that inadequate hemodynamic response will affect the prognostic value of PET MPI. METHODS AND RESULTS: Using a multicenter rubidium (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated rest/stress PET MPI with a vasodilator agent were analyzed. Patients were categorized as, "responders" [increase in heart rate ≥ 10 beats per minute (bpm) and decrease in systolic blood pressure (SBP) ≥10 mmHg], "partial responders" (either a change in HR or SBP), and "non-responders" (no change in HR or SBP). Primary outcome was all-cause death (ACD), and secondary outcome was cardiac death (CD). Ischemic burden was measured using summed stress score (SSS) and % left ventricular (LV) ischemia. After a median follow-up of 1.68 years (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n = 54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of 1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had higher AER with worsening levels of ischemic burden. In the presence of severe SSS ≥12 and LV ischemia of ≥10%, partial responders had an AER of 10.79% and 10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively. Patient classification was improved when SSS was added to a model containing clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI: 61%, p < 0.001). The model including clinical variables, SSS and hemodynamic response has good discrimination ability (Harrell C statistics: 0.77 [0.74-0.80]). CONCLUSION: Hemodynamic response during a vasodilator Rb-82 PET MPI is predictive of ACD. Partial and non-responders may require additional risk stratification leading to altered patient management.

Prognostic significance of blood pressure response during vasodilator stress Rb-82 positron emission tomography myocardial perfusion imaging.

BACKGROUND: 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. METHODS AND RESULTS: 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 <.10 were entered into the multivariable model. After median 1.7 years follow-up, 270 patients died. In univariate analyses, ∆SBP (P = .082), rSBP (P = .008), and rDBP (P < .001) were of potential prognostic value (P < .10), but ∆DBP was not (P = .96). After adjustment for other clinical and MPI variables, ∆SBP no longer independently predicted mortality (P = .082); only lower rSBP (P = .026) and lower rDBP (P = .045) remained independently prognostic. CONCLUSIONS: In patients undergoing vasodilator stress MPI, only lower resting BP is an independent predictor of mortality along with other clinical and MPI variables; BP response does not appear to add to risk stratification in these patients.

External validation of models for estimating pretest probability of coronary artery disease among individuals undergoing myocardial perfusion imaging.

BACKGROUND: Clinical decisions regarding the appropriateness of noninvasive cardiac imaging among individuals with suspected coronary artery disease (CAD) rely heavily on the pretest probability of coronary artery disease (pCAD), often estimated from clinical prediction models. These models have not been validated among individuals undergoing noninvasive myocardial perfusion imaging (MPI) for suspected CAD. Thus, the objective of this study was to compare the extent of agreement and predictive performance between four published pCAD models among individuals undergoing positron emission tomography (PET MPI). METHODS: This cross-sectional study performed at a cardiac referral center included 2383 patients with stable symptoms undergoing PET MPI for the evaluation of suspected CAD. pCAD was estimated on a per-patient basis using four distinct pCAD estimation models. All pCAD estimates were calibrated to a common standard to allow fair comparisons of agreement and predictive performance. Pairwise pCAD model disagreement was defined as percent discordance in classifying patients as low versus intermediate pCAD (<10% vs. ≥10%). Predictive performance was quantified by c-statistics with abnormal myocardial perfusion as a binary outcome. RESULTS: Pairwise pCAD estimates demonstrated non-negligible disagreement with percent discordance between models ranging from 11% to 23%. Agreement worsened when higher thresholds for distinguishing low-intermediate pCAD were employed. All pCAD models demonstrated poor predictive performance for identifying abnormal stress perfusion with c-statistics ranging from 0.554 to 0.616. CONCLUSIONS: pCAD estimation models showed suboptimal agreement and poor predictive performance in patients undergoing PET MPI. The transportability of pCAD models to MPI patients should be questioned and further evaluated in future studies.

Comparing changes in severe versus mild perfusion defect size in patients who underwent serial rubidium-82 positron emission tomography myocardial perfusion imaging.

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 activity <60% (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 (p <0.001) and mild perfusion defect sizes worsened (p <0.001) 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.

Prognostic value of PET myocardial perfusion imaging in obese patients.

OBJECTIVES: This study sought to determine and compare the prognostic and incremental value of positron emission tomography (PET) in normal, overweight, and obese patients. BACKGROUND: Cardiac 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. METHODS: A 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 (<25 kg/m(2)), overweight (25 to 29.9 kg/m(2)), or obese (≥30 kg/m(2)). Using a 17-segment model and 5-point scoring system, the percentage of abnormal myocardium was calculated for stress and rest patients categorized as normal (0%), mild (0.1% to 9.9%), moderate (10% to 19.9%), and severe (≥20%). RESULTS: A total of 6,037 patients were followed for cardiac death (median: 2.2 years) and the mean BMI was 30.5 ± 7.4 kg/m(2). A total of 169 cardiac deaths were observed. PET MPI demonstrated independent and incremental prognostic value over BMI. Normal PET MPI conferred an excellent prognosis with very low annual cardiac death rates in normal (0.38%), overweight (0.43%), and obese (0.15%) patients. As well, both moderately and severe obese patients with a normal PET MPI had excellent prognosis (0.20% and 0.10%, respectively). The net reclassification improvement of PET was 0.46 (95% confidence interval [CI]: 0.31 to 0.61), and appeared similar in the moderately and severe obese patients which were 0.44 (95% CI: 0.12 to 0.76) and 0.63 (95% CI: 0.27 to 0.98), respectively. CONCLUSIONS: Rb-82 PET has incremental prognostic value in all patients irrespective of BMI. In the obese population, where other modalities may have reduced diagnostic accuracy, cardiac PET appears to be a promising noninvasive modality with prognostic value.

Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET.

BACKGROUND: 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. METHODS: 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 <5%, 5-9.9%, and ≥ 10%. We estimated CAD mortality using univariable and multivariable Cox proportional hazard models. RESULTS: CAD mortality was 12.8%, 3.4%, and 0.8%, respectively, for HRR measurements of ≤ 4, 5-14, and ≥ 15 bpm (P < 0.0001). In a multivariable model, the HRR was independently predictive of CAD mortality (P < 0.0001) with adjusted hazard ratios elevated 3.5- and 8.4-fold for HRR of 5-14 and ≤ 4 versus ≥ 15 bpm. In a multivariable model, both the HRR and stress MPI % abnormal myocardium were independently and highly predictive of CAD mortality. Moreover, the net reclassification improvement was 0.18 for the HRR when compared to a model including risk factors, symptoms, rest HR, and PET variables (P = 0.0008). For those with ≥ 10% abnormal myocardium on stress PET, there was a graded relationship between HRR and CAD mortality with adjusted hazards exceeding 50-fold for measurements of 5-14 and ≤ 4 bpm (P < 0.0001) compared to stress MPI with <5% abnormal myocardium and a HRR ≥ 15 bpm. CONCLUSION: A diminished HRR to vasodilator stress is a novel but increasingly important predictor of CAD mortality. HRR measurements of ≤ 4, 5-14, and ≥ 15 bpm were independently predictive of CAD mortality and underscore the importance of optimizing readily available novel markers of risk as highly relevant to identifying high and low risk patient subsets.

Prognostic value of Rb-82 positron emission tomography myocardial perfusion imaging in coronary artery bypass patients.

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.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

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.

Association between neutrophil-lymphocyte ratio and impaired myocardial perfusion in patients with known or suspected coronary disease.

OBJECTIVE: To determine whether an elevated neutrophil-lymphocyte ratio (NLR) is associated with chronically impaired myocardial perfusion in patients with known or suspected coronary disease. BACKGROUND: Elevated NLRs are positively associated with cardiac events, anatomic coronary disease, and myocardial infarct size. However, no study has evaluated the association between NLR and chronically impaired myocardial perfusion. METHODS: This study included 683 patients undergoing cardiac positron emission tomography (PET) with a calculable NLR within 90 days of PET. The primary outcome was myocardial perfusion defect size measured in percent of left ventricular mass (%LV60). RESULTS: NLR was independently associated with %LV60 when analyzed as both a continuous and binary outcome (p < 0.001). Individuals with NLR above the 90th percentile had a 5-fold increased likelihood of significant perfusion defects compared to individuals with NLR between the 10th and 25th percentiles (Odds ratio = 4.7, p < 0.001). CONCLUSION: An elevated NLR demonstrated strong associations with myocardial perfusion.

Influence of sex on risk stratification with stress myocardial perfusion Rb-82 positron emission tomography: Results from the PET (Positron Emission Tomography) Prognosis Multicenter Registry.

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 < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset. 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.

Prognostic value of stress myocardial perfusion positron emission tomography: results from a multicenter observational registry.

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 classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD). BACKGROUND: Limited prognostic data are available for MPI with PET. METHODS: A total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed. RESULTS: Risk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death. CONCLUSIONS: In patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors.

Evaluating the prognostic value of positron-emission tomography myocardial perfusion imaging using automated software to calculate perfusion defect size.

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.

The prognostic association between resting heart rate and cardiac death--myocardial perfusion defects as a potential mechanism.

OBJECTIVE: Elevated resting heart rate (RHR) is a robust risk factor for cardiac events, and recent clinical trial evidence suggests lowering RHR may reduce cardiac risk among individuals with elevated RHR and known coronary artery disease (CAD). This study sought to elucidate the extent to which myocardial perfusion defects explain the association between RHR and cardiac death among individuals with known or suspected CAD undergoing myocardial perfusion imaging (MPI). METHODS: This retrospective cohort study included 3708 individuals with known or suspected CAD who underwent clinically indicated MPI with positron emission tomography (PET MPI). Stress, rest, and stress-induced myocardial perfusion defect sizes were measured objectively by automated computer software as percent of left ventricular myocardium hypoperfused. RHR was measured by electrocardiography prior to rest PET MPI. Cardiac and non-cardiac death information was obtained through the National Death Index. All analyses were stratified by beta blocker (BB) use. RESULTS: RHR was consistently associated with the presence of significant myocardial perfusion defects, though associations were stronger among BB than non-BB users. Among BB users, RHR was strongly associated with an increased risk of cardiac death in adjusted models before (hazard ratio [HR] = 2.6 comparing RHR ≥ 80 bpm vs. RHR<60, p<0.05) and after (HR = 2.4, p<0.05) including stress myocardial perfusion defect size in the model. Results were similarly strong among non-BB users. CONCLUSIONS: Resting heart rate was independently associated with cardiac death, however there was little evidence suggesting this association was explained by the presence of myocardial perfusion defects.

Elevated expression of the interleukin-8 receptors CXCR1 and CXCR2 in peripheral blood cells in obstructive coronary artery disease.

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.

Impact of myocardial perfusion imaging with PET and (82)Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management.

UNLABELLED: We hypothesized that PET myocardial perfusion imaging with (82)Rb (PET MPI), would reduce downstream utilization of diagnostic arteriography, compared with SPECT, in patients matched for pretest likelihood of coronary disease (pCAD). PET MPI is more accurate for assessment of impaired coronary flow reserve compared with SPECT MPI, potentially reducing the demand for subsequent arteriography, percutaneous trans-coronary intervention, and coronary artery bypass grafting (CABG), with attendant cost savings, while avoiding a negative impact on coronary events. METHODS: The frequency of diagnostic arteriography, revascularization, costs, and 1-y clinical outcomes in 2,159 patients studied with PET MPI was compared with 2 control groups studied with SPECT MPI matched to the PET group by pCAD: an internal control group of 102 patients and an external SPECT control group of 5,826 patients. CAD management costs were approximated with realistic global fee estimates. RESULTS: Arteriography rates were 0.34 and 0.31 for the external and internal control SPECT groups and 0.13 for the patients studied with PET (P < 0.0001). pCAD averaged 0.39 in patients studied with PET MPI, and in the external SPECT control group, and 0.37 in the internal SPECT controls. Revascularization rates were 0.13 and 0.11 for external and internal SPECT patients and 0.06 for the PET group (P < 0.0001; P < 0.01), with a cost savings of 30% noted for PET patients, with no significant difference in cardiac death or myocardial infarction at 1-y follow-up. CONCLUSION: PET MPI in patients with intermediate pCAD results in a >50% reduction in invasive coronary arteriography and CABG, a 30% cost savings, and excellent clinical outcomes at 1 y compared with SPECT.