Positron Emission Tomography Perfusion Research Articles

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion

BackgroundAmong patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. MethodsAI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4–8.3] years. Results662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n ​= ​147/331) vs. normal AI-QCTischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17–5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n ​= ​269/331) vs. normal AI-QCTischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58–2.02, p ​= ​0.794) (p-interaction ​= ​0.039). ConclusionAmong patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.

The Role of Magnetic Resonance Spectroscopy, Magnetic Resonance Perfusion and Positron Emission Tomography-Computed Tomography in Post-Radiotherapy Evaluation of Gliomas to Detect Recurrence

Abstract Background and Aim: In this article, the findings of magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion, and positron emission tomography (PET) will be compared and finally correlated with the histopathological examination in all patients having positive imaging findings. The sensitivity and specificity of MRS, MR perfusion, and PET in diagnosing residual/recurrent glioma would be estimated using the histopathological diagnosis as a gold standard. Materials and Methods: Twenty-nine cases of intracranial glioma that had undergone surgery, followed by adjuvant radiotherapy were enrolled in the study. All 29 patients underwent MRS, MR perfusion, and fluorodeoxyglucose (FDG) PET. Results: The sensitivity of MRS to detect recurrence was found to be 83.3% and specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) were 100% and 33.3%, respectively. The diagnostic accuracy of MRS was found to be 84.6%. The sensitivity and specificity of MR perfusion to detect recurrence were 91.7% and 100%, respectively. The diagnostic accuracy of MR perfusion is 92.3%. The NPV of MR perfusion was found to be 50%. The sensitivity of PET scans to detect recurrence was 83.3% and specificity was 100%. The PPV of PET was 100% and the NPV was 33.3%. The diagnostic accuracy of the PET scan was found to be 84.6%. Conclusions: Our study shows that all three modalities are useful, however, MR perfusion study is better than MRS and FDG PET in detecting recurrence. MR contrast with perfusion and spectroscopy and FDG PET scan should be included in the protocol for radiotherapy-treated gliomas to differentiate between radiation necrosis, postradiotherapy gliosis, and recurrent/residual tumor.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest

ObjectivesThis study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. MethodsEleven healthy subjects (eight men and three women) received intravenous XTR004 (239–290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. ResultsIn the first 0–12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. ConclusionsXTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

PET-determined myocardial perfusion and flow in coronary artery disease characterization

Positron emission tomography (PET) myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent assessment of myocardial perfusion and regional myocardial blood flow (MBF) of the left ventricle in absolute terms in milliliters per gram per minute (mL/g/min). The non-invasive quantification of MBF during pharmacologically induced hyperemia, at rest, and corresponding myocardial flow reserve (MFR) opens a new avenue for the identification and characterization of classical or endogen type of coronary microvascular dysfunction (CMD) as functional substrate for microvascular angina in patients with non-obstructive coronary artery disease (CAD) and/or no CAD at all. Further, PET-MBF quantification expands the scope of conventional myocardial perfusion imaging from the identification of advanced, and flow-limiting, epicardial CAD to early stages of atherosclerosis and/or CMD. Adding MBF assessment to myocardial perfusion may also reliably unravel diffuse ischemia owing to significant left main stenosis and/or multivessel CAD, confirmed by peak stress transient ischemic cavity dilation of the left ventricle during maximal vasomotor stress on gated PET images. Owing to high spatial and contrast resolution in conjunction with photon-attenuation free myocardial perfusion PET images, PET is preferentially used for CAD in advanced obesity and women with pronounced breast habitus. With increasing clinical use of cardiac PET perfusion and MBF assessment, individualized, and image-guided cardiovascular treatment decisions in CAD patients is likely to ensue, while its translation into improved cardiovascular outcome remains to be investigated.

Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

Coronary microvascular function in male physicians with burnout and job stress: an observational study

BackgroundAs a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events.MethodsThirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on coronary flow reserve (primary outcome) and two additional measures of coronary microvascular function in the same model while adjusting for age and body mass index.ResultsBurnout and job stress were significantly and independently associated with endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow response, and hyperemic myocardial blood flow (r partial = 0.28 to 0.35; p-value = 0.008 to 0.035). Effort-reward ratio (r partial =  − 0.32 to − 0.38; p-value = 0.004 to 0.015) and overcommitment (r partial =  − 0.30 to − 0.37; p-value = 0.005 to 0.022) showed inverse associations with these measures.ConclusionsIn male physicians, burnout and high job stress showed opposite associations with coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications and temporal relationships between work-related variables and coronary microvascular function. Future studies should include burnout and job stress for a more nuanced understanding of their potential role in cardiovascular health.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Association Between Global Sleep Quality and Coronary Microvascular Function in Male Physicians With Occupational Burnout.

Occupational burnout has been associated with an increased risk of coronary heart disease, although the mechanisms involved are elusive. We investigated whether poor global sleep quality is associated with impaired coronary microvascular function in male physicians, a professional group at increased risk of burnout. Study participants were 30 male physicians with clinical burnout and 30 controls without burnout defined by the Maslach Burnout Inventory. Global sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular functions were quantified with myocardial perfusion positron emission tomography. In multivariable analyses, the interaction between burnout and the PSQI global score was regressed on measures of coronary microvascular function, adjusting for age, body mass index, physical activity, alcohol consumption, and main effects of burnout and PSQI score. The prevalence of poor sleepers (PSQI score >5) was 40% in the burnout group and 10% in the control group. Adjusting for covariates, burnout-by-global PSQI score interactions were observed for myocardial blood flow (MBF) at rest ( r partial = -0.30, p = .025), endothelium-dependent coronary flow reserve ( r partial = -0.26, p = .062), MBF response ( r partial = -0.30, p = .028), and hyperemic MBF ( r partial = -0.34, p = .012). The global PSQI score was inversely associated with these MBF measures in the burnout group relative to the control group. No significant interactions emerged for endothelium-independent MBF. In male physicians with occupational burnout, poor global sleep quality was associated with reduced endothelium-dependent coronary microvascular function, suggesting a mechanism by which burnout may affect cardiovascular health.

Adenosine-induced splenic switch-off on [15O]H2O PET perfusion for the assessment of vascular vasodilatation

BackgroundSplenic switch-off (SSO) is a marker of adequate adenosine-induced vasodilatation on cardiac magnetic resonance perfusion imaging. We evaluate the feasibility of quantitative assessment of SSO in myocardial positron emission tomography (PET) perfusion imaging using [15O]H2O.MethodsThirty patients underwent [15O]H2O PET perfusion with adenosine stress. Time-activity curves, as averaged standardized uptake values (SUVavg), were extracted from dynamic PET for spleen and liver. Maximum SUVavg, stress and rest spleen-to-liver ratio (SLR), and the splenic activity concentration ratio (SAR) were computed. Optimal cut-off values for SSO assessment were estimated from receiver operating characteristics (ROC) curve for maximum SUVavg and SLR. Also, differences between coronary artery disease, myocardial ischemia, beta-blockers, and diabetes were assessed. Data are presented as median [interquartile range].ResultsIn concordance with the SSO phenomenon, both the spleen maximum SUVavg and SLR were lower in adenosine stress when compared to rest perfusion (8.1 [6.5, 9.2] versus 16.4 [13.4, 19.0], p < 0.001) and (0.81 [0.63, 1.08] versus 1.86 [1.73, 2.06], p < 0.001), respectively. During adenosine stress, the SSO effect was most prominent 40–160 s after radiotracer injection. Cut-off values of 12.6 and 1.57 for maximum SUVavg and SLR, respectively, were found based on ROC analysis. No differences in SAR, SLRRest, or SLRStress were observed in patients with coronary artery disease, myocardial ischemia, or diabetes.ConclusionsSSO can be quantified from [15O]H2O PET perfusion and used as a marker for adequate adenosine-induced vasodilatation response. In contrary to other PET perfusion tracers, adenosine-induced SSO is time dependent with [15O]H2O.

Incremental value of a CCTA-derived AI-based ischemia algorithm over standard CCTA interpretation for coronary ischemia in patients with suspected coronary artery disease

Abstract Background Coronary computed tomography angiography (CCTA) is a widely used non-invasive test to diagnose coronary artery stenosis in patients with suspected coronary artery disease (CAD). Positive predictive value for ischemia has been suboptimal using clinical reading. A novel AI-based ischemia algorithm applying machine learning that considers an array of atherosclerotic and vascular morphology features from CCTA images has been suggested to improve the diagnostic performance for ischemia. Purpose This study aims to evaluate the incremental diagnostic performance of CCTA derived AI-based ischemia algorithm in evaluating myocardial ischemia. Methods Patients with suspected CAD referred for CCTA at Turku University Hospital from February 2007 to December 2016 were analysed. The AI-based ischemia algorithm was calculated by analysts blinded for patient characteristics and clinical outcomes using typically-acquired CCTA images. In diagnostic reading significant stenosis defined by a stenosis &amp;gt; 50% on CCTA. The reference standard was ischemia detected by stress 15O-H2O positron emission tomography (PET). Results A total of 1445 patients (mean age 63 ± 9 years, 46% male) were included in this analysis. Myocardial ischemia by PET was detected in 384 (27%) patients while the other patients had either normal PET or had non-obstructive CAD by CCTA. A positive AI-based ischemia algorithm was found in 431 (30%) patients. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the AI-based ischemia algorithm for the assessment of myocardial ischemia were 83%, 74%, 86%, 66%, and 90%, respectively. Compared with diagnostic reading of CCTA (area under the receiver operating characteristic curve [AUC], 0.853; 95%CI 0.832-0.874), the model including clinical reading and AI-based ischemia algorithm demonstrated superior discrimination of myocardial ischemia (AUC 0.883; 95%CI 0.863-0.904, p-value &amp;lt;0.001). (Figure) Conclusions A novel AI-based ischemia algorithm derived from CCTA improves diagnostic accuracy compared with clinical reading of CCTA in assessing myocardial ischemia by PET perfusion imaging in patients with suspected CAD.Figure

Abstract 17343: Coronary Microvascular Function in Physician Burnout and Job Stress

Background: As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that seems more prevalent among male than female physicians. Aim: This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events. Methods: Thirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on measures of coronary microvascular function in the same model while adjusting for age and body mass index. Results: Burnout and job stress had significant and independent effects on endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow (MBF) response, and hyperemic MBF (r partial: 0.29 to 0.35; p-value: 0.008 to 0.027). Effort-reward ratio (r partial: -0.32 to -0.34; p-value: 0.009 to 0.017) and overcommitment (r partial: -0.29 to -0.35; p-value: 0.008 to 0.027) showed inverse associations with these measures. Conclusions: In male physicians, burnout and high job stress showed opposite effects on coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications. Future studies should include burnout and job stress for a more nuanced understanding of their potential impact on cardiovascular health.

Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion.

Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. In total, 6867 patients were included with a median follow-up of 3.4 years [1st-3rd quartiles, 1.9-5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37-2.97]) and global MFR (HR 2.29, 95%C.I. [2.08-2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46-1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03-1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183-0.310]). The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.

Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes

BackgroundMyocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear. MethodOverall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5–10%); and Group III (n = 155), moderate-to-severe (> 10%). ResultsCardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48–5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37–8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59–2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR. ConclusionImpaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

Incremental prognostic value of downstream positron emission tomography perfusion imaging after coronary computed tomography angiography: a study using machine learning.

To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. A total of 2411 patients with clinically suspected coronary artery disease (CAD) underwent CCTA, out of whom 891 patients were admitted to downstream PET MPI for haemodynamic evaluation of obstructive coronary stenosis. Two sets of Extreme Gradient Boosting (XGBoost) ML models were trained, one with all the clinical and imaging variables (including PET) and the other with only clinical and CCTA-based variables. Difference in the performance of the two sets was analysed by means of area under the receiver operating characteristic curve (AUC). After the removal of incomplete data entries, 2284 patients remained for further analysis. During the 8-year follow-up, 210 adverse events occurred including 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths. The PET MPI data improved the outcome prediction over CCTA during the first 4 years of the observation time and the highest AUC was at the observation time of Year 1 (0.82, 95% confidence interval 0.804-0.827). After that, there was no significant incremental prognostic value by PET MPI. PET MPI variables improve the prediction of adverse events beyond CCTA imaging alone for the first 4 years of follow-up. This illustrates the complementary nature of anatomic and functional information in predicting the outcome of patients with suspected CAD.

Prognostic Value of Modified Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [15O]H2O positron emission tomography perfusion imaging. Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction. During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P<0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P<0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P<0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P=0.017). [15O]H2O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [15O]H2O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.

Coronary artery calcium score and pre-test probabilities as gatekeepers to predict and rule out perfusion defects in positron emission tomography

BackgroundLittle is known about the gatekeeper performance of coronary artery calcium score (CACS) before myocardial perfusion positron emission tomography (PET), compared with updated pre-test probabilities from American and European guidelines (pre-test-AHA/ACC, pre-test-ESC).MethodsWe enrolled participants without known coronary artery disease undergoing CACS and Rubidium-82 PET. Abnormal perfusion was defined as summed stress score ≥ 4. Using Bayes’ formula, pre-test probabilities and CACS were combined into post-test probabilities.ResultsWe included 2050 participants (54% male, mean age 64.6 years) with median CACS 62 (IQR 0-380), pre-test-ESC 17% (11-26), pre-test-AHA/ACC 27% (16-44), and abnormal perfusion in 437 participants (21%). To predict abnormal perfusion, area under the curve of CACS was 0.81, pre-test-AHA/ACC 0.68, pre-test-ESC 0.69, post-test-AHA/ACC 0.80, and post-test-ESC 0.81 (P < 0.001 for CACS vs. each pre-test, and each post-test vs. pre-test). CACS = 0 had 97% negative predictive value (NPV), pre-test-AHA/ACC ≤ 5% 100%, pre-test-ESC ≤ 5% 98%, post-test-AHA/ACC ≤ 5% 98%, and post-test-ESC ≤ 5% 96%. Among participants, 26% had CACS = 0, 2% pre-test-AHA/ACC ≤ 5%, 7% pre-test-ESC ≤ 5%, 23% post-test-AHA/ACC ≤ 5%, and 33% post-test-ESC ≤ 5% (all P < 0.001).ConclusionsCACS and post-test probabilities are excellent predictors of abnormal perfusion and can rule it out with very high NPV in a substantial proportion of participants. CACS and post-test probabilities may be used as gatekeepers before advanced imaging.Graphical Summary: Prediction of Abnormal Perfusion in Position Emission Tomography Using Coronary Artery Calcium Score and Pre-Test ProbabilitiesCoronary artery calcium score (CACS) predicted abnormal perfusion (SSS ≥ 4) in myocardial positron emission tomography (PET) better than pre-test probabilities of coronary artery disease (CAD), while pre-test-AHA/ACC and pre-test-ESC performed similarly (left). Using Bayes’ formula, pre-test-AHA/ACC or pre-test-ESC were combined with CACS into post-test probabilities (middle). This calculation reclassified a substantial proportion of participants to low probability of CAD (0-5%), not needing further imaging, as shown for AHA/ACC probabilities (2% with pre-test-AHA/ACC to 23% with post-test-AHA/ACC, P < 0.001, right). Very few participants with abnormal perfusion were classified under pre-test or post-test probabilities 0-5%, or under CACS 0. AUC: area under the curve. Pre-test-AHA/ACC: Pre-test probability of the American Heart Association/American College of Cardiology. Post-test-AHA/ACC: Post-test probability combining pre-test-AHA/ACC and CACS. Pre-test-ESC: Pre-test probability of the European Society of Cardiology. SSS: Summed stress score.

The incremental value of PET perfusion imaging over coronary CT angiography in predicting outcome. A study using machine learning

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland, Turku University Hospital Background Coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) are powerful non-invasive tools to evaluate the patients with suspected coronary artery disease (CAD). Purpose The goal of this study was to evaluate the incremental value of these imaging methods in predicting short- and long-term cardiac events using machine learning (ML) approaches. Methods 2411 patients with clinically suspected CAD underwent coronary CTA and subsequent positron emission tomography (PET) MPI. Following our local routine, if obstructive CAD cannot be ruled-out by coronary CTA, PET MPI using 15O-water is performed. The incremental prognostic value of PET imaging was tested using several ML models of which XGBoost models consistently outperformed others and were chosen for further analyses. XGBoost models were trained by using clinical data from medical records and coronary imaging findings: one set of models used all the available variables, while a second set of models used only clinical and CTA-based variables. Differences in the performances of the models were then used to assess the incremental value of PET perfusion variables in outcome prediction. Results After the removal of incomplete data entries, data from 2284 patients was retained for further analysis. During 8-year follow-up period 210 patients had a major cardiac event (these endpoints correspond to 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths). The PET perfusion imaging data improved the predictive power of CTA during the first 4 years of observation time. After that, no significant difference in the predictive power was observed between the considered sets of XGBoost models, which either included or did not include PET perfusion data in the input variables. The highest area under the receiver operating characteristic curve (AUC) was at the observation time of 2 years (0.81, 95% CI 0.805–0.823) when PET data were included. The corresponding AUC when PET data were not included was at the observation time of 2 years (0.79, 95% CI 0.785–0.802). Conclusions Based on ML approach PET perfusion imaging improves the power in predicting cardiac events over anatomical CTA imaging for the first 4 years. The results illustrate the differences and complementary nature of anatomic and perfusion information in predicting outcome of patients with suspected CAD.