Emission Tomography Myocardial Perfusion Imaging Research Articles

Duration of adenosine-induced myocardial hyperemia - Insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging.

To assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared to a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects. Quantitative MBF at rest (rMBF), during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET-MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 minutes between adenosine infusion offset and rest-imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group (0.80 [IQR 0.66-1.00] vs. 0.70 [0.58-0.83] ml·min-1·g-1, p < 0.001) and, as sMBF was identical between groups (2.52 [2.20-2.96] vs. 2.50 [1.96-3.11], p = 0.347), MFR was significantly lower in the stress-rest group (3.07 [2.43-3.88] vs. 3.50 [2.63-4.10], p < 0.001). There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, p = 0.002) and between Δtstress-rest and MFR (r = 0.163, p = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest. Intravenously applied adenosine induces a long-lasting hyperemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR.

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.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW

ObjectivesThe objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). Background15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. MethodsThe RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies.Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan.The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. ConclusionsThe RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. Clinical trial registration informationClinical-Trials.gov (#NCT05134012).

Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy.

HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P<0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P=0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P=0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 (P=0.02). PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF. URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

Abstract 16514: Head-to-Head Comparison of Quantitative Image Quality on Rubidium-82 Myocardial Perfusion Positron Emission Tomography Between a Digital Silicon Photomultiplierand Conventional Scanner

Introduction: The purpose of this study was to compare rubidium-82 positron emission tomography ( 82 Rb PET) myocardial perfusion imaging (MPI) findings and quantitative image quality measures between the digital silicone photomultipliers (SiPM) scanner and a conventional scanner. Methods: We studied 24 consecutive patients (mean age 71.2±2.2 years) who underwent two clinically indicated rest/stress 82 Rb PET MPI examinations on two scanners, one using a SiPM-based PET scanner (Biograph Vision, Siemens Healthineers) and the other using a conventional photomultiplier tube (PMT)-based PET scanner (Discovery 710, GE Healthcare). Inclusion criteria were: 1) interval between the scans &lt;2 yr (median 1.1 yr, 95% CI: 0.9-1.4), 2) no interval revascularization, and 3) no interval symptom changes. Stress and imaging protocols were the same. 82 Rb doses were 925 MBq at rest and stress. Image quality was assessed using blood background coefficient-of-variation (COV), myocardium to blood signal to noise ratio (SNR) and contrast to noise ratio (CNR) calculated from the 82 Rb images. Results: Between two scanners, there were no significant differences in perfusion and functional measures, including summed stress score (SiPM: 1.6 ± 0.7 vs. PMT: 1.8 ± 0.8, p=0.21), summed rest score (SiPM: 2.7 ± 1.0 vs. PMT: 3.1 ± 1.2, p=0.34), LV function (LVEF, SiPM: 62.6 ± 2.8 vs. PMT: 61.4 ± 2.8, p=0.82) and volumes (LVEDV, SiPM: 62.6 ± 2.8 vs. PMT: 61.4 ± 2.8, p=0.51). Image quality measures significantly improved (Figure), with lower COV (SiPM: 15.3 ± 0.8 vs. PMT: 19.3 ± 1.1, p=0.006), higher SNR (SiPM; 26.4 ± 1.8 vs. PMT; 20.5 ± 1.5, p&lt;0.001) and CNR (SiPM; 14.2 ± 1.2 vs. PMT; 11.4 ± 1.1, p=0.02). Conclusions: 82 Rb PET MPI performed with SiPM-based a PET scanner showed significantly better image contrast and less noise compared to a PMT-based PET scanner. These findings suggest that the SiPM based PET scanner provides more previse evaluations for patients undergoing 82 Rb PET MPI.

Abstract 17801: Age-Specific Normal Values for Myocardial Blood Flow on 82rb Positron Emission Tomography

Introduction: Positron emission tomography (PET) myocardial perfusion imaging (MPI) is utilized to evaluate ischemia along with myocardial blood flow (MBF). The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is a measure of overall health of the coronary circulation and associated with lower major adverse cardiovascular events (MACE) and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease (CAD) has not been well established. Hypothesis/Aim: To determine the effect of age on MBF and MBFR in a cohort of patients without demonstrable CAD. Methods: Patients who underwent PET MPI studies from 2012-2022 on Siemens PET/CT cameras were included if Summed Stress Score=0, coronary calcium score=0, and left ventricular ejection fraction ≥50%. Those with prior history of MI or coronary intervention, heart/kidney/liver transplant, cirrhosis, or CKD stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City, MO) and multivariable linear regression models were developed to predict MBF. Results: Among 3,235 patients (age 59.5+/-12.6 years, 24.2% male) with median rest MBF 0.74 [0.61-0.92] and stress MBF 1.71 [1.41-2.10], MBFR was 2.28 [1.93-2.72]. With increasing age, rest MBF remained fairly stable while stress MBF and MBFR decreased, such that for every 10 years of age, stress MBF decreased by 0.07 [95% CI 0.05-0.08] mL/min/g and MBFR decreased by 0.12 [95% CI 0.11-0.14] after multivariable adjustment. Age-specific predicted MBFR values are documented in the Table. Conclusions: In patients without demonstrable CAD, the MBFR decreases with age. Abnormal MBFR values under 2.0 may be seen in a significant number of older patients.

Reproducibility of Left Ventricular Function Derived From Cardiac Magnetic Resonance and Gated 13N-Ammonia Positron Emission Tomography Myocardial Perfusion Imaging: A Head-to-Head Comparison Using Hybrid Positron Emission Tomography/Magnetic Resonance

Cardiac magnetic resonance (CMR) and gated 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) offer accurate and highly comparable global left ventricular ejection fraction (LVEF) measurements. In addition to accuracy, however, reproducibility is crucial to avoid variations in LVEF assessment potentially negatively impacting treatment decisions. We performed a head-to-head comparison of the reproducibility of LVEF measurements derived from simultaneously acquired CMR and PET-MPI using different state-of-the-art commercially available software. 93 patients undergoing hybrid PET/MR were retrospectively included. LVEF was derived from CMR and PET-MPI at two separate core labs, using two state-of-the-art software packages for CMR (cvi42 and Medis Suite MR) and PET (QPET and CardIQ Physio). Intra- and inter-reader agreement was assessed using correlation and Bland-Altman (BA) analyses. While intra- and inter-reader reproducibility of LVEF was high among both modalities and all software packages (r≥0.87 and ICC≥0.91, all significant at p<0.0001), LVEF derived from PET-MPI and analyzed with QPET outperformed all other analyses (intra-reader reproducibility: r=0.99, ICC=0.99; inter-reader reproducibility: r=0.98, ICC=1.00; Pearson correlations significantly higher than all others at p≤0.0001). BA analyses showed smaller biases for LVEF derived from PET-MPI (-0.1% and +0.9% for intra-reader, -0.4% and -0.8% for inter-reader agreement) than those derived from CMR (+0.7% and +2.8% for intra-reader, -0.9% and -2.2% for inter-reader agreement) with similar results for BA limits of agreement. Gated 13N-ammonia PET-MPI provides equivalent reproducibility of LVEF compared to CMR. It may offer a valid alternative to CMR for patients requiring LV functional assessment.

Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease.

Distinguishing obstructive epicardial coronary artery disease (CAD) from microvascular dysfunction and diffuse atherosclerosis would be of immense benefit clinically. However, quantitative measures of absolute myocardial blood flow (MBF) integrate the effects of focal epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. In this study, MFR and relative perfusion quantification were combined to create integrated MFR (iMFR) which was evaluated using data from a large clinical registry and an international multi-center trial and validated against invasive coronary angiography (ICA). This study included 1,044 clinical patients referred for 82Rb rest/stress positron emission tomography myocardial perfusion imaging and ICA, along with 231 patients from the Flurpiridaz 301 trial (clinicaltrials.gov NCT01347710). MFR and relative perfusion quantification were combined to create an iMFR map. The incremental value of iMFR was evaluated for diagnosis of obstructive stenosis, adjusted for patient demographics and pre-test probability of CAD. Models for high-risk anatomy (left main or three-vessel disease) were also constructed. iMFR parameters of focally impaired perfusion resulted in best fitting diagnostic models. Receiver-operating characteristic analysis showed a slight improvement compared to standard quantitative perfusion approaches (AUC 0.824 vs. 0.809). Focally impaired perfusion was also associated with high-risk CAD anatomy (OR 1.40 for extent, and OR 2.40 for decreasing mean MFR). Diffusely impaired perfusion was associated with lower likelihood of obstructive CAD, and, in the absence of transient ischemic dilation (TID), with lower likelihood of high-risk CAD anatomy. Focally impaired perfusion extent derived from iMFR assessment is a powerful incremental predictor of obstructive CAD while diffusely impaired perfusion extent can help rule out obstructive and high-risk CAD in the absence of TID.

Prevalence and Prognostic Importance of Abnormal Positron Emission Tomography Among Asymptomatic Patients With Diabetes Mellitus

BackgroundIschemia and reduced global myocardial blood flow reserve (MBFR) are associated with high cardiovascular risk among symptomatic patients with diabetes mellitus (DM). ObjectivesThis study aimed to assess the prevalence and prognostic importance of silent ischemia and reduced MBFR among asymptomatic patients with DM. MethodsThis study included 2,730 consecutive patients with DM, without known coronary artery disease (CAD) or cardiomyopathy, who underwent rubidium-82 rest/stress positron emission tomography (PET) myocardial perfusion imaging (MPI) from 2010 to 2016. These patients were followed up for all-cause mortality (n = 461) for a median follow-up of 3 years. Patients were considered asymptomatic if neither chest pain nor dyspnea was elicited. Rates of ischemia, reduced MBFR, and coronary microvascular dysfunction on PET were assessed in both groups. Cox regression was used to define the independent association of abnormal MPI markers with mortality. ResultsOne-quarter of patients with DM (23.7%; n = 647) were asymptomatic; ischemia was present in 30.5% (n = 197), reduced MBFR in 62.3% (n = 361), and coronary microvascular dysfunction in 32.7% (n = 200). In adjusted analyses, reduced MBFR (HR per 0.1 unit decrease in MBFR: 1.08 [95% CI: 1.03-1.12]; P = 0.001) and reduced ejection fraction (HR per 5% decrease: 1.10 [95% CI: 1.01-1.18]; P = 0.02) were independently prognostic of mortality among asymptomatic patients, but ischemia was not. This was comparable to DM patients with symptoms. Insulin use and older age were significant predictors of reduced MBFR among asymptomatic patients with DM. ConclusionsIn both symptomatic and asymptomatic patients with DM, impairment in MBFR is common and associated with greater mortality risk.

Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease

BackgroundFlurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. ObjectivesThe purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). MethodsIn this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ResultsA total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m2, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. ConclusionsThis second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273)

Impact of Positron Emission Tomographic Myocardial Perfusion Imaging on Patient Selection for Revascularization

BackgroundPositron emission tomography (PET) myocardial perfusion imaging (MPI) quantifies left ventricular ejection fraction (LVEF) at peak stress. PET LVEF reserve (LVEF-R = stress LVEF − rest LVEF) offers diagnostic and prognostic value. ObjectivesThe purpose of this study was to determine if PET LVEF-R identifies patients with survival benefit postrevascularization. MethodsWe followed 14,649 unique consecutive patients undergoing 82Rb rest/stress PET MPI from January 2010 to January 2016 (excluding known cardiomyopathy). Adjusted Cox models were built to predict all-cause death, and the 3-way interaction of known coronary artery disease (CAD) (prior myocardial infarction/revascularization), LVEF-R, and 90-day revascularization was tested. ResultsKnown CAD was present in 4,982 (34.0%). Ischemia was detected in 5,396 (36.8%; ≥10% in 1,909 [13%]). Mean LVEF-R was 4.2% ± 5.7%, and was ≤0, 1 to 5, and >5 in 3,349 (22.9%), 5,266 (35.9%), and 6,034 (41.2%). Over median follow-up of 3.4 years (IQR: 1.9-5.2 years), 1,324 (8.1%) had 90-day revascularization, and there were 2,192 (15.0%) deaths. In multivariable modeling, there was a significant 3-way interaction among known CAD, LVEF-R, and 90-day revascularization (P = 0.025), such that LVEF-R ≤0 identified patients with survival benefit with 90-day revascularization in those without prior CAD (interaction P = 0.005), independently beyond percent ischemia and myocardial flow reserve. Among patients with known CAD, LVEF-R was not prognostic of death (HR: 0.99; 95% CI: 0.98-1.02; P = 0.98). ConclusionsA lack of augmentation or drop in LVEF with vasodilator stress on PET MPI independently identifies patients who have better survival with revascularization within 90 days post-MPI compared with medical therapy, in absence of prior myocardial infarction or revascularization. Multiparametric assessment of ischemia with PET can optimize post-test management.

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.

Incremental prognostic value of stress phase entropy over standard PET myocardial perfusion imaging variables.

Phase analysis can assess left ventricular dyssynchrony. The independent prognostic value of phase variables over positron emission tomography myocardial perfusion imaging (PET-MPI) variables including myocardial flow reserve (MFR) has not been studied. The aim of this study was to explore the prognostic value of phase variables for predicting mortality over standard PET-MPI variables. Consecutive patients who underwent pharmacological stress-rest 82Rb PET study were enrolled. All PET-MPI variables including phase variables (phase entropy, phase bandwidth, and phase standard deviation) were automatically obtained by QPET software (Cedars-Sinai, Los Angeles, CA). Cox proportional hazard analyses were used to assess associations with all-cause mortality (ACM). In a total of 3963 patients (median age 71years; 57% male), 923 patients (23%) died during a median follow-up of 5years. Annualized mortality rates increased with stress phase entropy, with a 4.6-fold difference between the lowest and highest decile groups of entropy (2.6 vs. 12.0%/year). Abnormal stress phase entropy (optimal cutoff value, 43.8%) stratified ACM risk in patients with normal and impaired MFR (both p < 0.001). Among three phase variables, only stress phase entropy was significantly associated with ACM after the adjustment of standard clinical and PET-MPI variables including MFR and stress-rest change of phase variables, whether modeled as binary variables (adjusted hazard ratio, 1.44 for abnormal entropy [> 43.8%]; 95%CI, 1.18-1.75; p < 0.001) or continuous variables (adjusted hazard ratio, 1.05 per 5% increase; 95%CI, 1.01-1.10; p = 0.030). The addition of stress phase entropy to the standard PET-MPI variables significantly improved the discriminatory power for ACM prediction (p < 0.001), but the other phase variables did not (p > 0.1). Stress phase entropy is independently and incrementally associated with ACM beyond standard PET-MPI variables including MFR. Phase entropy can be obtained automatically and included in clinical reporting of PET-MPI studies to improve patient risk prediction.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion—a descriptive PET/MR myocarditis study

PurposeWhether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis.MethodsFifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18).ResultsCompared to remote segments, healed segments showed higher stress MBF (2.71 mL*min−1*g−1 [IQR 2.18–3.08] vs. 2.20 mL*min−1*g−1 [1.75–2.68], p < 0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p < 0.0001), and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE.ConclusionIn patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.Graphical abstractCMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Impact of myocardial inflammation on quantitative myocardial perfusion at long-term follow-up - a descriptive hybrid PET/MR myocarditis study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF). Background Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. Objectives To assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. Methods Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n=469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n=118), and scarred (LGE at follow-up, n=72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n=18). Results Compared to remote segments, healed segments showed higher stress MBF (2.71mL*min-1*g-1 [IQR 2.18–3.08] vs. 2.20 mL*min-1*g-1 [1.75–2.68], p&amp;lt;0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p&amp;lt;0.0001) and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ∼30% (p&amp;lt;0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with myocardial scar but without corresponding LGE. Conclusions In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also provides prognostic information. Purpose We evaluated sex differences in disease phenotype and adverse outcomes by using non-invasive combined anatomical and functional imaging in symptomatic patients with suspected CAD. Methods We retrospectively evaluated patients undergone coronary computed tomography angiography (CTA) for suspected CAD. According to local routine, patients with suspected obstructive stenosis on CTA were referred to downstream 15O-water positron emission tomography (PET) myocardial perfusion imaging to assess stress myocardial blood flow (MBF; ≤2.3 mL/g/min considered abnormal). A composite adverse endpoint was recorded, including all-cause death, myocardial infarction, and unstable angina pectoris. Results A total of 1948 patients (59% women) underwent coronary CTA of whom 657 (34%) patients underwent downstream PET perfusion imaging. During a mean follow-up of 6.8 years, 182 adverse events occurred. Women more often had normal coronary arteries (42% vs. 22%, p&amp;lt;0.001) and less often abnormal stress MBF (9% vs. 28%, p&amp;lt;0.001), as compared with men. The annual adverse event rate was lower in women versus men (1.2% vs. 1.7%, p = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0 and 5.6-fold adverse event rates in women and men, respectively. There was no statistical interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse outcome. Conclusion Among patients evaluated for chronic chest pain, women have lower prevalence of ischemic CAD and lower rate of future adverse events. Combined coronary CTA and PET myocardial perfusion imaging predicts outcomes equally in women and men.

Hybrid CTA/PET imaging of coronary artery disease in non-diabetic, prediabetic and diabetic patients evaluated for chest pain

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland Finnish foundation for cardiovascular research. Background Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and cardiac events. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). Purpose To study whether prediabetes or diabetes affects the relationship between imaging-defined CAD and patient outcome. Methods We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was routinely evaluated by 15O-water PET myocardial perfusion imaging. The relationship of CAD phenotype and long-term outcome was investigated according to patient’s diabetic status. A composite outcome included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris. Results A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of follow-up, 164 (9%) adverse events occurred, including 106 deaths, 41 MIs and 17 episodes of unstable angina. The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (i.e., obstructive stenosis and abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and to 27% in diabetic patients. The lowest event rate was seen in patients with normal coronary arteries (annual event rate 0.2%) and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings. Conclusions Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in type 2 diabetic, prediabetic, and non-diabetic patients.

The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging

BackgroundPatients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome.MethodsWe retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by 15O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP).ResultsA total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings.ConclusionsCoronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.

A comparison of cardiovascular imaging practices in Africa, North America, and Europe: two faces of the same coin

Abstract Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. There are significant differences in the burden of cardiovascular disease and associated risk factors, across high-income countries and low- and middle-income countries. Cardiac imaging by echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography myocardial perfusion imaging are well-established non-invasive tests that aid in the diagnosis, risk stratification, and management of various cardiac diseases. However, there are significant inequalities in availability and access to imaging modalities in low- and middle-income countries attributed to financial constraints, disparities in healthcare and technical infrastructure. In the post-COVID-19 pandemic era, these disparities are exaggerated by the continued technological advancements driving innovations in the field of cardiovascular (CV) imaging in high-income countries, while there is an urgent need to provide sustainable access to diagnostic imaging for patients in economically strained healthcare systems in regions like Africa. This review aims to highlight the inequalities in the burden of cardiac disease, associated risk factors, and access to diagnostic CV imaging tests, while also exploring the need for sustainable solutions to implementing CV imaging all over the world.