Background and Aims Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization.Methods Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0.Results Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025).Conclusions Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Aims:Quantitative rest-stress myocardial perfusion in millilitres per minute per gram among multiple 2D and 3D positron emission tomography-computed tomography (PET-CT) scanners is essential for personalized cardiac management and clinical trials. Accordingly, this study reports the accuracy and precision of quantitative rest-stress millilitres per minute per gram and coronary flow capacity among 2D and two different digital 3D silicon photomultiplier (SiPM) PET-CT scanners for quantifying the severity of coronary pathophysiology for clinical trials or guiding interventions vs. medical treatment. Methods and results:One hundred seventy-one participants underwent 748 paired serial rest or stress PET perfusion imaging in the same person on 'same day' or 'different days' using rubidium-82 (Rb-82) pharmacologic stress on 2D and two different digital 3D SiPM PET-CT scanners for global myocardial perfusion in millilitres per minute per gram. For methodological variability of 66 'same-day' serial paired PETs in the same person by 2D and two different 3D SiPM PET-CT scanners, rest-stress global myocardial millilitres per minute per gram had no significant bias (P = 0.464, mean difference 0.014 ± 0.21 mL/min/g) with coefficient of variation (COV) of ±14%. For methodological plus biological variability of 154 'different-day' serial paired PETs, rest-stress global perfusion had no significant bias (P = 0.136), mean difference (0.028 ± 0.33), and COV of ±20%. Coronary flow reserve had a small bias of 0.095 ± 0.57 (P = 0.041) and COV of ±20%. Coronary flow capacity was not different by Kolmogorov-Smirnov test (P = 0.99). Conclusion:For quantifying myocardial perfusion in the same person on 'same day' or 'different days' using Rb-82, 3D SiPM PET-CT is comparably reproducible to analogue 2D PET-CT with the HeartSee perfusion model as the basis for quantifying physiologic severity of coronary heart disease to guide clinical decision-making or randomized clinical trials confirming these outcomes.

BACKGROUND:Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion. METHOD:Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine). RESULTS:Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group. CONCLUSION:We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.

Background: Despite advances in management of chronic coronary artery disease (CAD), risk of major adverse cardiac events (MACE) remains high without reduced mortality benefit in revascularization trials. The randomized CENTURY trial tested a comprehensive strategy integrating intense lifestyle management, medical treatment to targets, and quantitative myocardial perfusion by PET to identify patients at high mortality risk for which revascularization reduced mortality. Methods: Patients with chronic CAD were randomly assigned to standard-care or comprehensive-care groups. Cardiac PET quantified physiological CAD severity at baseline, 2, and 5 years. Patients and referring physicians of standard-care group were blinded to PET results but severely abnormal Coronary Flow Capacity (CFC) was unblinded with referral for intervention.Findings: Between March 5, 2009 and April 13, 2017, 515 patients were assigned to comprehensive care and 513 to standard care. Over 5-years study period, the primary endpoint of change in baseline-to-final risk score (∆) for comprehensive care was improved compared with standard care (-∆1·1 vs +∆0·33; 95% CI -1·84 to -0·97; p<0·000). Secondary endpoints of death (24/515: 4·7% vs 42/513: 8·2%; p=0·023), death or MI (36/515: 7·0% vs 57/513: 11·1%; p=0·024), late revascularization (49/515: 9·5% vs 76/513: 14·8%; p=0·011) and MACE (105/515: 20·4% vs 153/512: 29·8%; p=0·0006) were lower for comprehensive care than for standard care. For CENTURY population with high prevalence of risk factors (99%), coronary calcifications (79%), abnormal rest-stress PET scans (41%), abnormal angiogram or coronary events (38%), PET derived CFC reduced interventions to primarily severe CFC at high mortality risk 45/1028 (4·4%) and reduced interventions in patients with non-severe CFC to 11/1028 (1.1%) (P <0.00001).Interpretation: The randomized CENTURY trial demonstrates that integrated intense lifestyle modification, medical treatment to targets, and quantitative CFC by PET reduce all-cause-death, death or MI, revascularization and MACE as an efficient "gatekeeper" to interventions with cost reduction for optimal outcomes.Trial Registration: ClinicalTrials.gov NCT00756379.Funding: Weatherhead Foundation and the Weatherhead Endowment at the University of Texas Health Sciences Centre, Houston, TX, USA.Declaration of Interest: The authors have no conflict of interest, receive no support or payments from any commercial source, are solely responsible for design and conduct of the study, analyses, drafting, editing and submitted manuscript. No authors have a relationship with industry related to this manuscript.Ethical Approval: The study was approved by the University of Texas–Houston Committee for the Protection of Human Subjects (UT-CPHS) after patients voluntarily signed written informed consent.

Subendocardial ischemia is commonly diagnosed but not quantified by imaging.This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90).Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.

Background Data on impact of financial hardship on coronary artery disease (CAD) remain incomplete. Methods Consecutive subjects referred for clinical rest/stress cardiac positron emission tomography (PET) were enrolled. Financial hardship is defined as patients’ inability to pay for their out-of-pocket expense for cardiac PET. Abnormal cardiac PET is defined as at least moderate relative perfusion defects at stress involving > 10% of the left ventricle or global coronary flow reserve ≤ 2.0. Patients were followed for major adverse cardiovascular event (MACE) comprised of all-cause mortality, non-fatal myocardial infarction, and late coronary revascularization. Results We analyzed a total of 4173 patients with mean age 65.6 ± 11.3 years, 72.2% men, and 93.6% reported as having medical insurance. Of these, 504 (12.1%) patients had financial hardship. On multivariable analysis, financial hardship associated with abnormal cardiac PET (odds ratio 1.377, p = 0.004) and MACE (hazard ratio 1.432, p = 0.010) and its association with MACE was mostly through direct effect with small proportion mediated by abnormal cardiac PET or known CAD. Conclusion Among patients referred for cardiac rest/stress PET, financial hardship independently associates with myocardial perfusion abnormalities and MACE; however, its effect on MACE is largely not mediated by abnormal myocardial perfusion or known CAD suggesting distinct impact of financial hardship beyond traditional risk factors and CAD that deserves attention and intervention to effectively reduced adverse outcomes. Having medical insurance does not consistently protect from financial hardship and a more preventive-oriented restructuring may provide better outcomes at lower cost.

BACKGROUND:Subendocardial ischemia is commonly diagnosed but not quantified by imaging. OBJECTIVES:This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes. METHODS:Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization. RESULTS:Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90). CONCLUSIONS:Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.

BACKGROUND:The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice. METHODS:The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization. CONCLUSIONS:The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.

Background PET quantitative myocardial perfusion requires correction for partial volume loss due to one-dimensional LV wall thickness smaller than scanner resolution. Methods We aimed to assess accuracy of risk stratification for death, MI, or revascularization after PET using partial volume corrections derived from two-dimensional ACR and three-dimensional NEMA phantoms for 3987 diagnostic rest-stress perfusion PETs and 187 MACE events. NEMA, ACR, and Tree phantoms were imaged with Rb-82 or F-18 for size-dependent partial volume loss. Perfusion and Coronary Flow Capacity were recalculated using different ACR- and NEMA-derived partial volume corrections compared by Kolmogorov-Smirnov statistics to standard perfusion metrics with established correlations with MACE. Results Partial volume corrections based on two-dimensional ACR rods (two equal radii) and three-dimensional NEMA spheres (three equal radii) over estimate partial volume corrections, quantitative perfusion, and Coronary Flow Capacity by 50% to 150% over perfusion metrics with one-dimensional partial volume correction, thereby substantially impairing correct risk stratification. Conclusions ACR (2-dimensional) and NEMA (3-dimensional) phantoms overestimate partial volume corrections for 1-dimensional LV wall thickness and myocardial perfusion that are corrected with a simple equation that correlates with MACE for optimal risk stratification applicable to most PET-CT scanners for quantifying myocardial perfusion.

OBJECTIVES This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization. BACKGROUND The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown. METHODS Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic followup over 10 years (mean 4.2 +/- 2.5 years) for all-cause mortality with and without revascularization. RESULTS Severely reduced CFR of 1.0 to 1.5 and stress perfusion .1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere .0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery specific stenosis not defined by global CFR or stress perfusion alone. CONCLUSIONS CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere .0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio. (J Am Coll Cardiol Img 2021;14:1020-34) (c) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Rationale We aimed to define the impact of variable arterial input function on myocardial perfusion severity that may misguide interventional decisions and relates to limited capacity of 3D PET for high-count arterial input function of standard bolus R-82. Methods We used GE Discovery-ST 16 slice PET-CT, serial 2D and 3D acquisitions of variable Rb-82 dose in a dynamic circulating arterial function model, static resolution and uniformity phantoms, and in patients with dipyridamole stress to quantify per-pixel rest and stress cc center dot min(-1)center dot g(-1), CFR and CFC with (+) and (-) 10% simulated change in arterial input. Results For intermediate, border zone severity of stress perfusion, CFR and CFC comprising 7% of 3987 cases, simulated arterial input variability of +/- 10% may cause over or underestimation of perfusion severity altering interventional decisions. In phantom tests, current 3D PET has capacity for quantifying high activity of arterial input and high-count per-pixel values of perfusion metrics per artery or branches. Conclusions Accurate, reproducible arterial input function is essential for at least 7% of patients at thresholds of perfusion severity for optimally guiding interventions and providing high-activity regional per-pixel perfusion metrics by 3D PET for displaying complex quantitative perfusion readily understood ("owned") by interventionalists to guide procedures.

Aims To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). Methods and results Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 +/- 0.55 vs. 2.14 +/- 0.53 for dipyridamole and 1.82 +/- 0.61 vs. 2.33 +/- 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 +/- 0.67 vs. 2.67 +/- 0.72 for dipyridamole and 1.84 +/- 0.33 vs. 2.31 +/- 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR <= 2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). Conclusion Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest–stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET (P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size–severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone.

Background— Different adenosine stress imaging protocols have not been systemically validated for absolute myocardial perfusion and coronary flow reserve (CFR) by positron emission tomography, where submaximal stress precludes assessing physiological severity of coronary artery disease. Methods and Results— In 127 volunteers, serial rest–stress positron emission tomography scans using rubidium-82 with various adenosine infusion protocols identified (1) the protocol with maximum stress perfusion and CFR, (2) test–retest precision in same subject, (3) stress perfusion and CFR after adenosine compared with dipyridamole, (4) heterogeneity of coronary flow capacity combining stress perfusion and CFR, and (5) potential relevance for patients with risk factors or coronary artery disease. The adenosine 6-minute infusion with rubidium-82 injection at 3 minutes caused CFR that was significantly 15.7% higher than the 4-minute adenosine infusion with rubidium-82 injection at 2 minutes and significantly more homogeneous by Kolmogorov–Smirnov analysis for histograms of 1344 pixel range of perfusion in paired positron emission tomographies. In a coronary artery disease cohort separate from volunteers of this study, compared with the 3/6-minute protocol, the 2/4-minute adenosine protocol would potentially have changed 332 of 1732 (19%) positron emission tomographies at low-risk physiological severity CFR ≥2.3 to CFR <2.0, thereby implying high-risk quantitative severity potentially appropriate for interventions but because of suboptimal stress of the 2/4 protocol in some patients. Conclusions— The 6-minute adenosine infusion with rubidium-82 activation at 3 minutes produced CFR that averaged 15.7% higher than that in the 2/4-minute protocol, thereby potentially providing essential information for personalized management in some patients.

OBJECTIVES Positron emission tomography (PET) quantifies stress myocardial perfusion (in cc/min/g) and coronary flow reserve to guide noninvasively the management of coronary artery disease. This study determined their test-retest precision within minutes and daily biological variability essential for bounding clinical decision-making or risk stratification based on low flow ischemic thresholds or follow-up changes.BACKGROUND Randomized trials of fractional flow reserve-guided percutaneous coronary interventions established an objective, quantitative, outcomes-driven standard of physiological stenosis severity. However, pressure-derived fractional flow reserve requires invasive coronary angiogram and was originally validated by comparison to noninvasive PET.METHODS The time course and test-retest precision of serial quantitative rest-rest and stress-stress global myocardial perfusion by PET within minutes and days apart in the same patient were compared in 120 volunteers undergoing serial 708 quantitative PET perfusion scans using rubidium 82 (Rb-82) and dipyridamole stress with a 2-dimensional PET-computed tomography scanner (GE DST 16) and University of Texas HeartSee software with our validated perfusion model.RESULTS Test-retest methodological precision (coefficient of variance) for serial quantitative global myocardial perfusion minutes apart is +/- 10% (mean Delta SD at rest +/- 0.09, at stress +/- 0.23 cc/min/g) and for days apart is +/- 21% (mean Delta SD at rest +/- 0.2, at stress +/- 0.46 cc/min/g) reflecting added biological variability. Global myocardial perfusion at 8 min after 4-min dipyridamole infusion is 10% higher than at standard 4 min after dipyridamole.CONCLUSIONS Test-retest methodological precision of global PET myocardial perfusion by serial rest or stress PET minutes apart is +/- 10%. Day-to-different-day biological plus methodological variability is +/- 21%, thereby establishing boundaries of variability on physiological severity to guide or follow coronary artery disease management. Maximum stress increases perfusion and coronary flow reserve, thereby reducing potentially falsely low values mimicking ischemia. (C) 2017 by the American College of Cardiology Foundation.

In the wake of the Food and Drug Administration (FDA) recall, many clinics have had to reduce their examination volumes to meet the new generator volume usage requirements. This review tests 3 common infusion methods and how they affect patient dose, generator volume usage, image counts, and generator volume limits. Methods: Three common configurations of the Rb-82 infusion system settings-standard 50-mL, volume-limiting, and bolus methods-were tested to determine how they affect patient dose, generator volume, and image counts. Each injection configuration was tested daily for the duration of 3 consecutive generators by injection into separate vials. Each injection configuration was also infused into a beaker and imaged to determine the impact of image counts for each method. The total estimated volumes for multiple examination and quality assurance clinical situations were simulated to observe the use of each method relative to the new FDA volume alert and expiration limits. Results: Vial tests confirmed that the bolus method used the least amount of volume per infusion and stayed the most consistent throughout the life of the generator. The bolus method also produced a lower patient dose after approximately 10 d of use. The beaker tests in the scanner showed that the standard 50-mL method produced the greatest number of total counts for the flow and uptake images. On the basis of the estimated total volume simulations, the bolus method allowed for the most examinations over the life of the generator while staying within the new FDA limits. Conclusion: All 3 methods for augmenting the Rb-82 infusion system produced different outcomes for patient dose, image counts, and total generator volume use. The standard 50-mL method ensured the maximum amount of counts available for imaging throughout the life of the generator. The bolus method provided a consistent and predictable amount of volume use. The volume-limiting method fell somewhere in the middle of volume predictability and count preservation.