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Background: Quantitative myocardial blood flow (MBF) on positron-emission tomography myocardial perfusion imaging is a measure of the overall health of the coronary circulation. The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is associated with lower major adverse cardiovascular events and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease have not been well established. We aimed to determine the effect of age and sex on MBF in a cohort of patients without demonstrable coronary artery disease., Methods: Patients who underwent positron-emission tomography myocardial perfusion imaging studies from 2012 to 2022 on positron-emission tomography/computed tomography cameras were included if the summed stress score was 0, the coronary calcium score was 0, and the left ventricular ejection fraction was ≥50%. Those with known coronary artery disease, prior history of coronary intervention, diabetes, heart/kidney/liver transplant, cirrhosis, or chronic kidney disease stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City), and quantile regression models were developed to predict MBF., Results: Among 2789 patients (age 59.9±13.0 years, 76.4% females), median rest MBF was 0.73 (0.60-0.91) mL/min·g, stress MBF was 1.72 (1.41-2.10) mL/min·g, and MBFR was 2.31 (1.96-2.74). Across all ages, males augmented MBF in response to vasodilator stress to a greater degree than females but achieved lower absolute stress MBF. Younger males in particular achieved a higher MBFR than their female counterparts, and this gap narrowed with increasing age. Predicted MBFR for a 20-year-old male was 3.18 and female was 2.50, while predicted MBFR for an 80-year-old male was 2.17 and female was 2.02., Conclusions: In patients without demonstrable coronary artery disease, MBFR is higher in younger males than younger females and decreases with age in both sexes. Age- and sex-specific MBFR may be important in risk prediction and guidance for revascularization and warrant further study., Competing Interests: Dr Bateman has received research grant support from Bracco, GE Healthcare, Jubilant Drax Image, and Spectrum Dynamics; has served as a consultant to GE Healthcare and Synektik; and has an equity interest in Cardiovascular Imaging Technologies. The other authors report no conflicts.

Background: Myocardial perfusion imaging (MPI) identifies abnormalities that occur early in the ischemic cascade leading to angina. Our aim was to study the association between ischemic measures on positron emission tomography MPI and patients' health status; their symptoms, function, and quality of life., Methods: Health status was collected using the Seattle Angina Questionnaire (SAQ-7, 0-100, higher=better) and Rose Dyspnea Score (RDS) on 1515 outpatients with known or suspected coronary artery disease presenting for clinically indicated pharmacological 82 Rb positron emission tomography MPI from July 2018 to July 2019. Adjusted multivariable ordinal regression models were used to assess the association between MPI findings of ischemia and the SAQ physical limitation, angina frequency, quality of life, summary score, and the RDS., Results: The mean SAQ and RDS scores of the cohort (mean age 71.7 years, 55% male, 37.6% prior myocardial infarction or revascularization) were 73.8±28.6 (physical limitation), 87.4±21.7 (angina frequency), 79.0±26.1 (quality of life), 81.3±19.0 (summary score), and 2±2 (RDS). No perfusion, flow or function abnormalities were significantly associated with SAQ angina frequency scores. Low left ventricular ejection fraction reserve (≤0%), low global and regional myocardial blood flow reserve (<2) were independently associated with worse SAQ Physical Limitation score, SAQ summary score, and RDS (30% to 57% greater odds; all P ≤0.01), but reversible perfusion defects were not., Conclusions: Impaired augmentation of left ventricular ejection fraction and myocardial blood flow with stress is associated with significant angina-associated functional limitation, health status, and dyspnea in patients who underwent positron emission tomography MPI, but not the frequency of their angina. Future studies should evaluate whether therapies that improve stress-induced abnormalities in systolic function and myocardial flow may improve patients' health status.

Background: Phase analysis of single-photon emission computed tomography myocardial perfusion imaging provides dyssynchrony information which correlates well with assessments by echocardiography, but the independent prognostic significance is not well defined. This study assessed the independent prognostic value of single-photon emission computed tomography-myocardial perfusion imaging phase analysis in the largest multinational registry to date across all modalities., Methods: From the REFINE SPECT (Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT), a total of 19 210 patients were included (mean age 63.8±12.0 years and 56% males). Poststress total perfusion deficit, left ventricular ejection fraction, and phase variables (phase entropy, bandwidth, and SD) were obtained automatically. Cox proportional hazards analyses were performed to assess associations with major adverse cardiac events (MACE)., Results: During a follow-up of 4.5±1.7 years, 2673 (13.9%) patients experienced MACE. Annualized MACE rates increased with phase variables and were ≈4-fold higher between the second and highest decile group for entropy (1.7% versus 6.7%). Optimal phase variable cutoff values stratified MACE risk in patients with normal and abnormal total perfusion deficit and left ventricular ejection fraction. Only entropy was independently associated with MACE. The addition of phase entropy significantly improved the discriminatory power for MACE prediction when added to the model with total perfusion deficit and left ventricular ejection fraction ( P <0.0001)., Conclusions: In a largest to date imaging study, widely representative, international cohort, phase variables were independently associated with MACE and improved risk stratification for MACE beyond the prediction by perfusion and left ventricular ejection fraction assessment alone. Phase analysis can be obtained fully automatically, without additional radiation exposure or cost to improve MACE risk prediction and, therefore, should be routinely reported for single-photon emission computed tomography-myocardial perfusion imaging studies.

Objectives: This study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis., Background: Quantitative analysis has not been compared with clinical visual analysis in prognostic studies., Methods: A total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE., Results: During follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001)., Conclusions: Quantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study compared the clinical effectiveness of pharmacologic stress myocardial perfusion imaging (MPI) plus positron emission tomography (PET) with single-photon emission computed tomography (SPECT) in patients with known coronary artery disease (CAD) presenting with symptoms suggestive of ischemia., Background: Although PET MPI has been shown to have higher diagnostic accuracy in detecting hemodynamically significant CAD than SPECT MPI, whether this impacts downstream management has not been formally evaluated in randomized trials., Methods: This study consisted of a single-center trial in which patients with known CAD and suspected ischemia were randomized to undergo PET or attenuation-corrected SPECT MPI between June 2009 and September 2013. Post-test management was at the discretion of the referring physician, and patients were followed for 12 months. The primary endpoint was diagnostic failure, defined as unnecessary angiography (absence of ≥50% stenosis in ≥1 vessel) or additional noninvasive testing within 60 days of the MPI. Secondary endpoints were post-test escalation of antianginal therapy, referral for angiography, coronary revascularization, and health status at 3, 6, and 12 months., Results: A total of 322 patients with an evaluable MPI were randomized (n = 161 in each group). At baseline, 88.8% of patients were receiving aspirin therapy, 76.7% were taking beta-blockers, and 77.3% were taking statin therapy. Diagnostic failure within 60 days occurred in only 7 patients (2.2%) (3 [1.9%] in the PET group and 4 [2.5%] in the SPECT group; p = 0.70). There were no significant differences between the 2 groups in subsequent rates of coronary angiography, coronary revascularization, or health status at 3, 6, and 12 months of follow-up (all p values ≥0.20); however, when subjects were stratified by findings on MPI in a post hoc analysis, those with high-risk MPI on PET testing had higher rates of angiography and revascularization on follow-up than those who had SPECT MPI, whereas those undergoing low-risk PET studies had lower rates of both procedures than those undergoing SPECT (interaction between randomized modality ∗high-risk MPI for 12-month catheterization [p = 0.001] and 12-month revascularization [p = 0.09])., Conclusions: In this contemporary cohort of symptomatic CAD patients who were optimally medically managed, there were no discernible differences in rates of diagnostic failure at 60 days, subsequent coronary angiography, revascularization, or patient health status at 1 year between patients evaluated by pharmacologic PET compared with those evaluated by SPECT MPI. Downstream invasive testing rates with PET MPI were more consistent with high-risk features than those with SPECT MPI. (Effectiveness Study of Single Photon Emission Computed Tomography [SPECT] Versus Positron Emission Tomography [PET] Myocardial Perfusion Imaging; NCT00976053)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study evaluated the automatic prediction of obstructive disease from myocardial perfusion imaging (MPI) by deep learning as compared with total perfusion deficit (TPD)., Background: Deep convolutional neural networks trained with a large multicenter population may provide improved prediction of per-patient and per-vessel coronary artery disease from single-photon emission computed tomography MPI., Methods: A total of 1,638 patients (67% men) without known coronary artery disease, undergoing stress 99m Tc-sestamibi or tetrofosmin MPI with new generation solid-state scanners in 9 different sites, with invasive coronary angiography performed within 6 months of MPI, were studied. Obstructive disease was defined as ≥70% narrowing of coronary arteries (≥50% for left main artery). Left ventricular myocardium was segmented using clinical nuclear cardiology software and verified by an expert reader. Stress TPD was computed using sex- and camera-specific normal limits. Deep learning was trained using raw and quantitative polar maps and evaluated for prediction of obstructive stenosis in a stratified 10-fold cross-validation procedure., Results: A total of 1,018 (62%) patients and 1,797 of 4,914 (37%) arteries had obstructive disease. Area under the receiver-operating characteristic curve for disease prediction by deep learning was higher than for TPD (per patient: 0.80 vs. 0.78; per vessel: 0.76 vs. 0.73: p < 0.01). With deep learning threshold set to the same specificity as TPD, per-patient sensitivity improved from 79.8% (TPD) to 82.3% (deep learning) (p < 0.05), and per-vessel sensitivity improved from 64.4% (TPD) to 69.8% (deep learning) (p < 0.01)., Conclusions: Deep learning has the potential to improve automatic interpretation of MPI as compared with current clinical methods., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Under the auspices of the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC), an appropriateness review was conducted for radionuclide cardiovascular imaging (RNI), specifically gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The review assessed the risks and benefits of the imaging test for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid range (4 to 6) implies that the test may be generally acceptable and may be a reasonable approach for the indication. The indications for this review were primarily drawn from existing clinical practice guidelines and modified based on discussion by the ACCF Appropriateness Criteria Working Group and the Technical Panel members who rated the indications. The method for this review was based on the RAND/UCLA approach for evaluating appropriateness, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first- and second-round ratings of 52 clinical indications. The ratings were done by a Technical Panel with diverse membership, including nuclear cardiologists, referring physicians (including an echocardiographer), health services researchers, and a payer (chief medical officer). These results are expected to have a significant impact on physician decision making and performance, reimbursement policy, and future research directions. Periodic assessment and updating of criteria will be undertaken as needed.

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into "classical" (predominantly related to hyperemic MBFs) and "endogen" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials. [Display omitted] • Chest pain in patients without obstructive coronary artery disease constitutes a frequent clinical problem. • Coronary microvascular dysfunction may reflect a functional substrate underlying chest pain and shortness of breath symptoms. • Positron emission tomography MBF quantification can identify coronary microvascular dysfunction noninvasively. • Grouping hyperemic MBFs and MFR into "classical" and "endogen" normal coronary microvascular function or CMD, respectively, provides a framework for standardized reporting needed for diagnostic, treatment, and outcome clinical CMD trials. • In case of normal hyperemic MBFs and MFR, further evaluation of the presence of microvascular vasospasm, predominantly with invasive testing, may be considered in the appropriate clinical context. [ABSTRACT FROM AUTHOR]