Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve.

PURPOSE: We evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: The study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study. RESULTS: During a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001). CONCLUSIONS: In patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Prediction of outcome by 82Rb PET/CT in patients with ischemia and nonobstructive coronary arteries.

BACKGROUND: The purpose of this study was to assess the prognostic value of cardiac 82Rb positron emission tomography (PET)/computed tomography (CT) imaging in patients with myocardial ischemia of nonobstructive coronary arteries (INOCA). METHODS: We retrospectively evaluated 311 INOCA patients who underwent rest stress 82Rb PET/CT. Cardiac end points were cardiac death, myocardial infarction, or late coronary revascularization. A parametric survival model was also used to identify how the variables influenced time to event. RESULTS: During a median follow-up of 37 months (range 6-108), 23 (7%) cardiac events occurred. In patients with events total perfusion defect (TPD) was higher and myocardial flow reserve (MFR) lower compared to those without events (both P < .001). At multivariable Cox analysis, increased TPD (i.e., ≥ 5%) and reduced MFR (i.e., < 2) were predictors of events (both P < .001). At Weibull survival analysis, the highest probability of cardiac events and risk acceleration were observed in patients with both increased TPD and reduced MFR. Annualized event rate was higher in patients with reduced MFR compared to those with preserved MFR (P < .001). CONCLUSION: In patients with INOCA, the combined evaluation of myocardial perfusion and coronary vascular function by 82Rb PET/CT is able to identify those at higher risk of cardiac events.

A preliminary evaluation of a high temporal resolution data-driven motion correction algorithm for rubidium-82 on a SiPM PET-CT system.

BACKGROUND: In myocardial perfusion PET, images are acquired during vasodilator stress, increasing the likelihood of intra-frame motion blurring of the heart in reconstructed static images to assess relative perfusion. This work evaluated a prototype data-driven motion correction (DDMC) algorithm designed specifically for cardiac PET. METHODS: A cardiac torso phantom, with a solid defect, was scanned stationary and being manually pulled to-and-fro in the axial direction with a random motion. Non-motion-corrected (NMC) and DDMC images were reconstructed. Total perfusion deficit was measured in the defect and profiles through the cardiac insert were defined. In addition, 46 static perfusion images from 36 rubidium-82 MPI patients were selected based upon a perception of motion blurring in the images. NMC and DDMC images were reconstructed, blinded, and scored on image quality and perceived motion. RESULTS: Phantom data demonstrated near-perfect recovery of myocardial wall visualization and defect quantification with DDMC compared with the stationary phantom. Quality of clinical images was NMC: 10 non-diagnostic, 31 adequate, and 5 good; DDMC images: 0 non-diagnostic, 6 adequate, and 40 good. CONCLUSION: The DDMC algorithm shows great promise in rubidium MPI PET with substantial improvements in image quality and the potential to salvage images considered non-diagnostic due to significant motion blurring.

The prevalence of image degradation due to motion in rest-stress rubidium-82 imaging on a SiPM PET-CT system.

BACKGROUND: Motion of the heart is known to affect image quality in cardiac PET. The prevalence of motion blurring in routine cardiac PET is not fully appreciated due to challenges identifying subtle motion artefacts. This study utilizes a recent prototype Data-Driven Motion Correction (DDMC) algorithm to generate corrected images that are compared with non-corrected images to identify visual differences in relative rubidium-82 perfusion images due to motion. METHODS: 300 stress and 300 rest static images were reconstructed with DDMC and without correction (NMC). The 600 DDMC/NMC image pairs were assigned Visual Difference Score (VDS). The number of non-diagnostic images were noted. A "Dwell Fraction" (DF) was derived from the data to quantify motion and predict image degradation. RESULTS: Motion degradation (VDS = 1 or 2) was evident in 58% of stress images and 33% of rest images. Seven NMC images were non-diagnostic-these originated from six studies giving a 2% rate of non-diagnostic studies due to motion. The DF metric was able to effectively predict image degradation. The DDMC heart identification and tracking was successful in all images. CONCLUSION: Motion degradation is present in almost half of all relative perfusion images. The DDMC algorithm is a robust tool for predicting, assessing and correcting image degradation.

Diagnostic value of clinical risk scores for predicting normal stress myocardial perfusion imaging in subjects without coronary artery calcium.

BACKGROUND: We evaluated if risk scores commonly used to predict the absence of significant stenosis at coronary computed tomography (CT) angiography are useful to predict a normal stress myocardial perfusion imaging (MPI) study. METHODS: Our cohort included a total of 1422 consecutive patients with zero coronary artery calcium score (ZCS) who underwent 82Rb PET/CT for evaluation of suspected coronary artery disease (CAD). Predictive models were constructed as reported by Genders et al. and Alshahrani et al., and the probability of abnormal summed stress score (SSS) and of reduced myocardial perfusion reserve (MPR) based on these risk scores was assessed. RESULTS: In the overall population, the prevalence of abnormal SSS was 0.10 and the prevalence of reduced MPR was 0.17 (both P < .001).The observed frequencies of abnormal SSS and reduced MPR vs the probabilities predicted by the Genders and Alshahrani models were above the diagonal identity line, highlighting an underestimation of the observed occurrence by these models. The areas under the receiver operating characteristic curve of the Genders and Alshahrani models indicated lack of discriminative ability for predicting abnormal SSS (0.547 and 0.527) and reduced MPR (0.509 and 0.538). The Hosmer-Lemeshow test revealed that both models underestimated the observed occurrence of abnormal SSS and reduced MPR. CONCLUSIONS: Available models were unable to identify among patients with ZCS those with a low probability of a normal stress MPI study. Thus, an optimal approach to rule out from MPI patients without detectable coronary calcium still needs to be improved.

Prognostic value of coronary vascular dysfunction assessed by rubidium-82 PET/CT imaging in patients with resistant hypertension without overt coronary artery disease.

PURPOSE: The identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD). METHODS: We studied 517 hypertensive subjects, 26% with RH, without overt CAD, and with normal stress-rest myocardial perfusion imaging at 82Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure. RESULTS: Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05) and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time. CONCLUSION: The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.

Assessment of motion correction in dynamic rubidium-82 cardiac PET with and without frame-by-frame adjustment of attenuation maps for calculation of myocardial blood flow.

BACKGROUND: Patient motion during pharmacological stressing can have substantial impact on myocardial blood flow (MBF) estimated from dynamic PET. This work evaluated a motion correction algorithm with and without adjustment of the PET attenuation map. METHODS: Frame-by-frame motion correction was performed by three users on 30 rubidium-82 studies. Data were divided equally into three groups of motion severity [mild (M1), moderate (M2) and severe (M3)]. MBF data were compared for non-motion corrected (NC), motion-corrected-only (MC) and with adjustment of the attenuation map (MCAC). Percentage differences of MBF were calculated in the coronary territories and 17-segment polar plots. Polar plots of spill-over were also generated from the data. RESULTS: Median differences of 23% were seen in the RCA and 18% for the LAD in the M3 category for MC vs NC images. Differences for MCAC vs MC images were considerably smaller and typically < 10%. Spill-over plots for MC and MCAC were notably more uniform compared with NC images. CONCLUSION: Motion correction for dynamic rubidium data is desirable for future MBF software updates. Adjustment of the PET attenuation map results in only marginal differences and therefore is unlikely to be an essential requirement. Assessing the uniformity of spill-over plots is a useful visual aid for verifying motion correction techniques.

Prognostic value of coronary risk factors, exercise capacity and single photon emission computed tomography in liver transplantation candidates: A 5-year follow-up study.

BACKGROUND: Although consensus-based guidelines support noninvasive stress testing prior to orthotopic liver transplantation (OLT), the optimal screening strategy for assessment of coronary artery disease in patients with end-stage liver disease (ESLD) is unclear. This study sought to determine the relative predictive value of coronary risk factors, functional capacity, and single photon emission computed tomography (SPECT) on major adverse cardiovascular events and all-cause mortality in liver transplantation candidates. METHODS: Prior to listing for transplantation, 404 consecutive ESLD patients were referred to a University hospital for cardiovascular (CV) risk stratification. All subjects met at least one of the following criteria: inability to perform > 4 METs by history (62%), insulin-treated diabetes mellitus (53%), serum creatinine > 1.72 mg/dL (8%), history of MI, PCI or CABG (5%), stable angina (3%), cerebrovascular disease (1%), peripheral vascular disease (1%). Subjects underwent Technetium-99m SPECT with multislice coronary artery calcium scoring (CACS) using exercise treadmill or standard adenosine stress in those unable to achieve 85% maximal heart rate (Siemens Symbia T16). Abnormal perfusion was defined as a summed stress score (SSS) ≥ 4. RESULTS: Of the 404 patients, 158 (age 59 ± 9 years; male 68%) subsequently underwent transplantation and were included in the primary analysis. Of those, 50 (32%) died after a mean duration follow-up of 5.4 years (maximal 10.9 years). Most deaths (78%) were attributed to noncardiovascular causes (malignancy, sepsis, renal failure). Of the 32 subjects with abnormal perfusion (20%), nine (6%) had a high-risk perfusion abnormality defined as a total perfusion defect size (PDS) ≥ 15% and/or an ischemic PDS ≥ 10%. Kaplan-Meier survival curves demonstrated abnormal perfusion was associated with increased CV mortality (generalized Wilcoxon, P = 0.014) but not all-cause death. Subjects with both abnormal perfusion and an inability to exercise > 4 METs had the lowest survival from all-cause death (P = 0.038). Abnormal perfusion was a strong independent predictor of CV death (adjusted HR 4.2; 95% CI 1.4 to 12.3; P = 0.019) and MACE (adjusted HR 7.7; 95% CI 1.4 to 42.4; P = 0.018) in a multivariate Cox regression model that included age, sex, diabetes, smoking and the ability to exercise > 4 METs. There was no association between CACS and the extent of perfusion abnormality, nor with outcomes. CONCLUSIONS: Most deaths following OLT are noncardiovascular. Nonetheless, abnormal perfusion is prevalent in this high-risk population and a stronger predictor of cardiovascular morbidity and mortality than functional status. A combined assessment of functional status and myocardial perfusion identifies those at highest risk of all-cause death. (Exercise Capacity and Single Photon Emission Computed Tomography in Liver Transplantation Candidates [ExSPECT]; ClinicalTrials.gov Identifier: NCT03864497).

Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging.

BACKGROUND: We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD). METHODS: We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2. RESULTS: During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR. CONCLUSIONS: Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients.

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome.

PURPOSE: Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC), stress-induced myocardial ischemia and myocardial perfusion reserve (MPR). We evaluated the prognostic role of the combined assessment of regional CAC score, ischemic total perfusion defect (ITPD) and MPR in predicting lesion-related outcome in patients with suspected coronary artery disease (CAD). METHODS: We studied 206 patients with suspected CAD referred to 82Rb PET/CT cardiac imaging and available coronary angiographic data. The outcome end points were cardiac death, target vessel-related myocardial infarction or coronary revascularization. RESULTS: Compared to vessels without event, those with event showed higher CAC score and ITPD, and lower hyperemic myocardial blood flow and MPR (all p < 0.001). At Cox regression multivariable analysis, significant CAD (≥50% stenosis) (p < 0.001), CAC score ≥ 300 (p < 0.01) and MPR <2 (p < 0.01) were independent predictors of events. The decision trees analysis for the identification of events produced five terminal nodes. The initial split was on CAC score values. For vessels with CAC <300 and MPR ≥2, no further split was performed, while vessels with CAC <300 and MPR <2 were further stratified by ITPD. For vessels with CAC ≥300 a further stratification was performed only by MPR. The worst prognosis was observed in vessels with CAC ≥300 and MPR <2 and in vessels with CAC <300, MPR <2 and ITPD ≥5%. CONCLUSION: The combination of CAC score and MPR is useful to predict the lesion-related outcome in the presence of significant CAD.

Assessing time-of-flight signal-to-noise ratio gains within the myocardium and subsequent reductions in administered activity in cardiac PET studies.

BACKGROUND: Time-of-flight (TOF) is known to increase signal-to-noise ratio (SNR) and facilitate reductions in administered activity. Established measures of SNR gain are derived from areas of uniform uptake, which is not applicable to the heterogeneous uptake in cardiac PET images using fluoro-deoxyglucose (FDG). This study aimed to develop a technique to quantify SNR gains within the myocardium due to TOF. METHODS: Reference TOF SNR gains were measured in 88 FDG oncology patients. Phantom data were used to translate reference SNR gains and validate a method of quantifying SNR gains within the myocardium from parametric images produced from multiple replicate images. This technique was applied to 13 FDG cardiac viability patients. RESULTS: Reference TOF SNR gains of +23% ± 8.5% were measured in oncology patients. Measurements of SNR gain from the phantom data were in agreement and showed the parametric image technique to be sufficiently robust. SNR gains within the myocardium in the viability patients were +21% ± 2.8%. CONCLUSION: A method to quantify SNR gains from TOF within the myocardium has been developed and evaluated. SNR gains within the myocardium are comparable to those observed by established methods. This allows guidance for protocol optimization for TOF systems in cardiac PET.

Coronary vascular age: An alternate means for predicting stress-induced myocardial ischemia in patients with suspected coronary artery disease.

BACKGROUND: Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). METHODS: A total of 717 subjects referred to CAC scoring and 82Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). RESULTS: Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P < .001) in patients with ischemia compared to those without. At incremental analysis, the global Chi square increased from 41.26 to 68.77 (P < .001) when chronological age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P < .001). Adding chronological age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. CONCLUSIONS: In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

Impact of pharmacological stress agent on patient motion during rubidium-82 myocardial perfusion PET/CT.

BACKGROUND: Patient motion has been demonstrated to have a significant impact on the quality and accuracy of rubidium-82 myocardial perfusion PET/CT. This study aimed to investigate the effect on patient motion of two pharmacological stressing agents, adenosine and regadenoson. METHODS AND RESULTS: Dynamic data were retrospectively analyzed in 90 patients undergoing adenosine (n = 30), incremental adenosine (n = 30), or regadenoson (n = 30) rubidium-82 myocardial perfusion PET/CT. Severity of motion was scored qualitatively using a four-point (0-3) scale and quantitatively using frame-to-frame pixel shifts. The type of motion, returning or non-returning, and the frame in which it occurred were also recorded. There were significant differences in both the qualitative and quantitative scores comparing regadenoson to adenosine (P = .025 and P < .001) and incremental adenosine (P = .014, P = .015), respectively. The difference in scores between adenosine and incremental adenosine was not significant. Where motion was present, significantly more adenosine patients were classed as non-returning (P = .018). The median frames for motion occurring were 12 for regadenoson and 14 for both adenosine cohorts. CONCLUSIONS: The choice of stressing protocol impacts significantly on patient motion. Patients stressed with regadenoson have significantly lower motion scores than those stressed with adenosine, using local protocols. This motion is more likely to be associated with a drift of the heart away from a baseline position, coinciding with the termination of infusion.

The impact of prompt gamma compensation on myocardial blood flow measurements with rubidium-82 dynamic PET.

BACKGROUND: Rubidium-82 myocardial perfusion imaging is a well-established technique for assessing myocardial ischemia. With continuing interest on myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements, there is a requirement to fully appreciate the impact of technical aspects of the process. One such factor for rubidium-82 is prompt gamma compensation (PGC). This study aims to assess the impact of PGC on MBF and MFR calculated from dynamic Rb-82 data. METHODS: Dynamic rest and stress images were acquired on a Siemens Biograph mCT and reconstructed with and without PGC in 50 patients (29 male). MBF and MFR were measured in the three main coronary territories as well as globally. RESULTS: With PGC, statistically significant reductions in MBF were observed in LAD (-6.9%), LCx (-4.8%), and globally (-6.5%) but only in obese patients. Significant increases in MBF were observed in RCA (+6.4%) in only nonobese patients. In very obese patients, differences of up to 40% in MBF were observed between PGC and non-PGC images. In nearly all cases, similar PGC differences were observed at stress and rest so there were no significant differences in MFR; however, in a small number of very obese patients, differences in excess of 20% were observed. CONCLUSION: PGC results in statistically significant changes in MBF, with the greatest reductions observed in the LAD and LCx territories of obese patients. In most cases, the impact on stress and rest data is of similar relative magnitudes and changes to MFR are small.

Prognostic value of atherosclerotic burden and coronary vascular function in patients with suspected coronary artery disease.

PURPOSE: To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD). METHODS: We studied 436 patients undergoing hybrid 82Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0, <400, and ≥400). CFR was calculated as the ratio of hyperemic to baseline myocardial blood flow, and it was considered reduced when <2. RESULTS: Follow-up was 94% complete during a mean period of 47±15 months. During follow-up, 17 events occurred (4% cumulative event rate). Event-free survival decreased with worsening of CAC score category (p < 0.001) and in patients with reduced CFR (p < 0.005). At multivariable analysis, CAC score ≥400 (p < 0.01) and CFR (p < 0.005) were independent predictors of events. Including CFR in the prognostic model, continuous net reclassification improvement was 0.51 (0.14 in patients with events and 0.37 in those without). At classification and regression tree analysis, the initial split was on CAC score. For patients with a CAC score < 400, no further split was performed, while patients with a CAC score ≥400 were further stratified by CFR values. Decision curve analyses indicate that the model including CFR resulted in a higher net benefit across a wide range of decision threshold probabilities. CONCLUSIONS: In patients with suspected CAD, CFR provides significant incremental risk stratification over established cardiac risk factors and CAC score for prediction of adverse cardiac events.

Coronary atherosclerotic burden vs. coronary vascular function in diabetic and nondiabetic patients with normal myocardial perfusion: a propensity score analysis.

PURPOSE: To assess the relationship between coronary atherosclerotic burden and vascular function in diabetic and nondiabetic patients after balancing for coronary risk factors. METHODS: We studied 672 patients without overt coronary artery disease and normal myocardial perfusion on stress 82Rb PET/CT imaging. To account for differences in baseline characteristics between diabetic patients and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. RESULTS: Before matching, diabetic patients had higher coronary artery calcium (CAC) scores (p < 0.001) and lower coronary flow reserve (CFR; p < 0.001) than nondiabetic patients. After matching, CAC scores were comparable between diabetic and nondiabetic patients, but diabetic patients still had lower hyperaemic myocardial blood flow (p < 0.001) and CFR (p < 0.05). Patients were categorized by ln(CAC score) quartiles. There was a decrease in CFR with increasing CAC score quartile in both diabetic patients (p for trend < 0.01) and nondiabetic patients (p for trend < 0.005). Diabetes was associated with lower CFR across quartile categories (p < 0.002). In a multivariable linear regression analysis, CAC score was inversely related to CFR in both diabetic patients (p < 0.05) and nondiabetic patients (p < 0.001). CONCLUSION: Diabetic patients had higher CAC scores than nondiabetic patients, but the difference disappeared when clinical characteristics were taken into account. Of note, diabetic patients also had lower CFR regardless of CAC score than nondiabetic patients after matching. Thus, coronary atherosclerotic burden and vascular function have to be seen as two different entities.