Positron Emission Tomography Myocardial Perfusion Imaging Research Articles

Prognostic value of quantitative anatomical and functional measures of coronary artery disease in diabetic and non-diabetic patients

Abstract Background Diabetes is associated with increased risk of coronary artery disease (CAD). However, the relative prognostic importance of anatomical and functional findings of CAD in the presence vs. absence of diabetes is incompletely understood. Technological advances have made quantitative analysis of coronary artery plaques and stenosis feasible by coronary computed tomography angiography (CTA). In turn, positron emission tomography (PET) enables absolute quantification of myocardial blood flow (MBF). Purpose To study long-term prognostic value of quantified severity of coronary atherosclerosis and myocardial perfusion in non-diabetic vs. diabetic patients with suspected CAD. Methods From two academic medical centres, we identified symptomatic patients with suspected CAD who had undergone coronary CTA and [15O]H2O PET myocardial perfusion imaging during adenosine stress. Based on artificial intelligence -guided quantitative analysis of coronary CTA scans, the anatomical severity of CAD was measured as the presence of obstructive CAD (≥50% diameter stenosis) and percent atheroma volume (PAV; higher vs. lower than median). The functional severity of CAD was measured as the presence of regional myocardial ischemia (≥2 adjacent segments with stress MBF <2.3 ml/g/min) and global stress MBF (<2.2 ml/g/min vs. ≥ 2.2 ml/g/min) by PET. Annual rates of adverse events (AER) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were evaluated. Results Among 1311 patients, 251 (19%) had diabetes. Patients with diabetes had more frequently obstructive CAD (55% vs. 43%, p<0.001) and regional myocardial ischemia (51% vs. 43%, p=0.015), higher plaque burden by PAV (12% vs. 7%, p<0.001), and lower global stress MBF (2.78 ml/g/min vs. 3.05 ml/g/min, p<0.001). During median follow-up of 7.1 years, 171 (13.0%) patients experienced AE (85 deaths, 56 MIs, and 30 UAPs). Patients with diabetes had higher AER than non-diabetic patients (3.1% vs. 1.6%, p<0.001). The presence of obstructive stenosis was associated with increased AER in non-diabetic (2.6% vs. 1.0%, p<0.001) and diabetic patients (4.2% vs. 1.9%, p<0.001). High plaque burden by PAV was associated with increased AER in non-diabetic (2.8% vs. 0.7%, p<0.001) and diabetic patients (3.9% vs. 1.7%, p<0.001). The presence of regional myocardial ischemia was associated with increased AER in non-diabetic (2.5% vs. 1.1%, p<0.001), but not in diabetic patients (3.4% vs. 2.7%, p=0.238). Low global stress MBF was associated with increased AER in non-diabetic (2.9% vs. 1.3%, p<0.001), but not among diabetic patients (3.2% vs. 3.0%, p=0.286). Conclusions Diabetes was associated with more advanced CAD. Quantified severity of anatomical findings predicted long-term adverse outcome in non-diabetic and diabetic patients. In contrast, functional imaging risk stratified non-diabetic patients, whereas diabetic patients had impaired long-term outcome irrespective of perfusion findings.

Effect of acute intravenous beta-blocker administration on myocardial blood flow during same-day hybrid CCTA/PET imaging

This study aimed to evaluate the impact of acute intravenous beta-blocker administration on myocardial blood flow (MBF) during same-day hybrid coronary computed tomography angiography (CCTA) and 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI). Previous research on the discontinuation of oral beta-blockers before MPI has shown mixed results, with no studies yet exploring the acute intravenous administration in the context of same-day hybrid imaging. This retrospective study included patients with suspected chronic coronary syndromes undergoing same-day hybrid CCTA/13N-ammonia PET MPI. Exclusion criteria comprised coronary artery stenosis ≥ 50% or regional perfusion abnormalities on PET, and baseline oral beta-blocker medication. Intravenous metoprolol (up to 30 mg) was administered as needed for heart rate control before CCTA. MBF measurements were obtained at rest (rMBF) and during stress (sMBF), and myocardial flow reserve (MFR) was calculated. After excluding 281 patients, 154 were eligible for propensity-score matching, resulting in 108 patients divided into two equal groups based on beta-blocker administration. The groups showed no significant differences in baseline characteristics. Among those who received beta-blockers, there was a significant decrease in sMBF (2.21 [IQR 1.72–2.78] versus 2.46 [2.08–2.99] ml∙min−1∙g−1, p = 0.027) and MFR (3.46 [2.70–4.05] versus 3.79 [3.22–4.46], p = 0.030), respectively, compared to those who did not receive beta-blockers. In contrast, rMBF remained unaffected (0.65 [0.54–0.78] versus 0.64 [0.55–0.76] ml∙min−1∙g−1, p = 0.931). Acute intravenous beta-blocker administration significantly impacts MBF, leading to a slight reduction in sMBF and MFR. In contrast, rMBF appears unaffected, suggesting that beta-blockers primarily affect the coronary capacity to respond to vasodilators.

Age- and Sex-Specific Myocardial Blood Flow Values in Patients Without Coronary Atherosclerosis on Rb-82 PET Myocardial Perfusion Imaging.

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. 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. 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. 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.

Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease

BackgroundThe epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI. MethodsWe retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0. ResultsAmong 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET). ConclusionsCardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.

Quantitative myocardial perfusion in liver transplantation candidates: Poorly metabolized caffeine inhibition of vasodilatory stress

BackgroundData 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. MethodConsecutive 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). ResultsPrevalence 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. ConclusionWe 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.

Duration of adenosine-induced myocardial hyperaemia: insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging.

This study aimed to assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared with 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) and 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 min 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 (interquartile range 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 = 0.007]. 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 hyperaemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR.

Guiding early revascularization using [15O]H2O PET myocardial perfusion imaging - Impact of atrial fibrillation.

Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated whether atrial fibrillation (AF): 1) reduces global hyperemic myocardial blood flow (MBF) and 2) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD and AF-CAD. Hyperemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way ANOVA p<0.0001]. In multiple linear regression ongoing AF was independently associated with reduced hyperemic MBF. Every 0.1 mL/min/g decrease in hyperemic MBF was associated with a 23% increase in odds of early revascularization. ROC-analysis of vessel specific hyperemic MBF to predict early revascularization yielded the following areas under the ROC curve (AUC): SR-noCAD: 0.95 (p<0.0001); AF-noCAD: 0.79 (p<0.0001); SR-CAD: 0.78 (p<0.0001); AF-CAD: 0.88 (p<0.0001). Ongoing AF is associated with 19-25 % reduced global hyperemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel specific hyperemic MBF still predicts early revascularization in patients with AF.

Cardiovascular risk factors and development of nomograms in an Italian cohort of patients with suspected coronary artery disease undergoing SPECT or PET stress myocardial perfusion imaging.

Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive nuclear medicine techniques that can identify areas of abnormal myocardial perfusion. We assessed the prevalence of cardiovascular risk factors in patients with suspected coronary artery disease (CAD) undergoing SPECT or PET stress myocardial perfusion imaging (MPI). Based on significant risk factors associated with an abnormal MPI, we developed a nomogram for each cohort as a pretest that would be helpful in decision-making for clinicians. A total of 6,854 patients with suspected CAD who underwent stress myocardial perfusion imaging by SPECT or PET/CT was studied. As part of the baseline examination, clinical teams collected information on traditional cardiovascular risk factors: age, gender, body mass index, angina, dyspnea, diabetes, hypertension, hyperlipidemia, family history of CAD, and smoking. The prevalence of cardiovascular risk factors was different in the two cohorts of patients undergoing SPECT (n = 4,397) or PET (n = 2,457) myocardial perfusion imaging. A statistical significance was observed in both cohorts for age, gender, and diabetes. At multivariable analysis, only age and male gender were significant covariates in both cohorts. The risk of abnormal myocardial perfusion imaging related to age was greater in patients undergoing PET (odds ratio 4% vs. 1% per year). In contrast, male gender odds ratio was slightly higher for SPECT compared to PET (2.52 vs. 2.06). In the SPECT cohort, smoking increased the risk of abnormal perfusion of 24%. Among patients undergoing PET, diabetes and hypertension increased the risk of abnormal perfusion by 63% and 37%, respectively. For each cohort, we obtained a nomogram by significant risk factors at multivariable logistic regression. The area under the receiver operating characteristic curve associated with the nomogram was 0.67 for SPECT and 0.73 for the PET model. Patients with suspected CAD belonging to two different cohorts undergoing SPECT or PET stress myocardial perfusion imaging can have different cardiovascular risk factors associated with a higher risk of an abnormal MPI study. As crude variables, age, gender, and diabetes were significant for both cohorts. Net of the effect of other covariates, age and gender were the only risk factors in common between the two cohorts. Furthermore, smoking and type of stress test were significant for the SPECT cohort, where as diabetes and hypertension were significant for the PET cohort. Nomograms obtained by significant risk factors for the two cohorts can be used by clinicians to evaluate the risk of an abnormal study.

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.

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.

Abstract 15719: Prognostic Interplay Between Myocardial Flow Reserve and Left Ventricular Ejection Fraction

Introduction: Myocardial flow reserve (MFR), measured using positron emission tomography (PET), has been shown to add incremental prognostic value in multiple patient populations. Whether this association is modified by left ventricular ejection fraction (LVEF) is not well studied. The aim of this analysis is to determine whether there is a prognostic interplay between myocardial flow reserve and LVEF. Methods: The study population included patients who had clinically indicated PET myocardial perfusion imaging and were prospectively followed for incident events. MFR was calculated as the ratio of stress to rest myocardial blood flow (MBF) (ml/min/g). Rest LVEF was calculated from end systolic and end diastolic LV volumes on gated images. Cox proportional hazards were used to study the association between MFR (&lt;2 vs ≥2) and incident cardiovascular events stratified by LVEF (&lt;50% vs ≥50%). Results: The study population included 5,523 patients (mean±SD age 67±12 years, 53% male), 16% of LVEF&lt;50% and 47% MFR &lt;2. Rest MBF was similar among patients with normal or reduced LVEF while stress MFR was lower with lower EF. In adjusted analysis, patients with impaired MFR had a higher incident event rate regardless of LVEF (Figure 1). Patients with MFR&lt;2 had a higher risk of incident outcomes in both LVEF ≥50% (HR=2.58, 95% CI:1.93 - 3.46, p&lt;0.001) and LVEF &lt;50% (HR=2.76, 95% CI: 1.62 - 4.70, p&lt;0.001); p-value for interaction= 0.045. Conclusions: Impaired MFR is associated with a higher risk of cardiovascular outcomes and death in patients with high or low LVEF.

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.

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)

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

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.

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.

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.

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.