Positron Emission Tomography Myocardial Perfusion Imaging Research Articles

Low coronary flow reserve in patients with long-standing persistent atrial fibrillation is associated with worse clinical outcomes

Abstract Funding Acknowledgements Type of funding sources: None. Background / Introduction Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction, stroke and all-cause mortality. Myocardial perfusion imaging (MPI) is well-established for the diagnosis of coronary artery disease (CAD) and risk-stratification in sinus rhythm (SR) patients. Purpose The aim of this study was to determine the prognostic impact of AF and coronary flow reserve (CFR) in patients undergoing positron emission tomography (PET) MPI. Methods 680 patients without a known history of CAD were included. 226 paroxysmal AF (PAF) and 114 long-standing persistent AF (LSPAF) patients were identified from a prospective PET MPI registry in the Isala Hospital and propensity matched in a 1:1 ratio to SR patients. The main indications for PET MPI were chest pain and dyspnea. Follow-up was obtained for the occurrence of major adverse cardiac and cerebrovascular events (MACCE, composite of myocardial infarction (MI), stroke/transient ischemic attack (TIA) or all-cause death). Results Compared with patients with PAF, patients with LSPAF were older (p=0.011) and more frequently male (p=0.031), with no significant differences in medical history. There were no significant differences between SR and AF in the occurrence of MACCE during a mean follow-up of 36 months. However, the incidence of downstream coronary angiography (p<0.001) and MACCE (p=0.028) was higher in patients with LSPAF compared to those with PAF and SR. A low CFR (defined as CFR below the median of 2.4) in patients with LSPAF showed significantly more MACCE compared with SR and PAF (p<0.001). Moreover, LSPAF was an independent predictor of MACCE (odds ratio 1.667, 95% confidence interval 1.028±2.705). Conclusion Low CFR in patients with LSPAF is associated with a higher incidence of MI, stroke/TIA and death compared with low and normal coronary flow parameters in patients with SR and PAF.

Impact of rubidium imaging availability on management of patients with acute chest pain

ObjectiveEvaluate the impact of 82-Rubidium positron emission tomography (PET) myocardial perfusion imaging (MPI) availability on patient management presenting at the emergency department (ED) with chest pain (CP). MethodsThis is a single-center retrospective study of clinical databases. Patients presenting with CP with a non-definitive suspicion of acute coronary syndrome (ACS) at the ED between April 2016 and February 2020 were divided into 2 groups based on PET availability. The proportion of invasive coronary angiography (ICA) without significant coronary artery disease (CAD), length of stay (LoS), and additional downstream testing were evaluated. ResultsThere were 21,242 ED visits for CP without definitive ACS: 5,492 when PET is not available and 15,750 when PET is available. When PET is available, proportion of patients undergoing a MPI study was greater (20.7% vs 17.6%, P<0.0001), proportion of ICA without significant CAD was similar (18.5% vs 21.4%, P=0.24), and median ED LoS was shorter (16.6 vs 18.1 hours, P=0.03). Patients undergoing SPECT MPI had significantly more downstream testing (8.9% vs 6.4%, P=0.003) and a higher rate of coronary angiogram without significant CAD (21.2% vs 14.2%, P=0.09) compared to those who underwent PET MPI. ConclusionAvailability of PET MPI was associated with an increased number of MPI referral from the ED, similar rates of ICA without significant CAD, decreased LoS, and fewer downstream testing.

Нарушения эндотелий-зависимой вазодилатации у больных с микрососудистой стенокардией

Background: disorders of both endothelium-dependent and endothelium-independent vasodilation play a role in the pathogenesis of microvascular angina (MVA), the contribution of which may be different. Aim: to study the processes of endothelium-dependent vasodilation (EDV) in patients with primary MVA. Patients and Methods: an open prospective study included 60 patients (mean age 57.3±6.4 years) with MVA, confirmed clinical picture (chest pain), coronary angiography data (the absence of coronary artery stenosis), positive stress test (pain syndrome and/or ST segment depression by ≥2 mm by treadmill exercise stress test), positron emission tomography (PET) myocardial perfusion imaging (MPI) with tests (cold pressor test and with adenosine). Patients with diseases that can lead to secondary microvascular dysfunction were not included in the study. To evaluate the processes of EDV, all patients underwent the following evaluations: peripheral arterial tonometry (PAT), assessment of circulating endothelial cells (CEC), high-sensitivity C-reactive protein (hsCRP), endothelin-1 (ET-1), total antioxidant status. Adding that, the results of a cold pressor test during PET were analyzed. Results: the majority of the examined patients were women — 81.7%. Most of the female patients included in the study (93.9%) were postmenopausal. In all patients with MVA, according to the data of PET MPI with cold pressor test, signs of EDV disorder were detected as a decrease in coronary blood flow through the three coronary arteries. During PET, the index of reactive hyperemia was reduced (&lt;1,67) in all examined patients and amounted to 1.43±0.15. According to the results of laboratory studies, there was an increase in the level of ET-1 and CEC — 3,335 [1,545; 3,952] fmol/L and 14±8 cells/3×105 leukocytes, respectively. The CRP level was 4,44 [1.02; 4.45] mg/L. The total antioxidant capacity was reduced in 53 (88%) patients, the average values of the indicator were 289,03±52,14 μmol/L. Conclusion: according to laboratory and instrumental studies, signs of endothelial dysfunction, namely disorders of EDV, were revealed in all examined patients with primary MVA. KEYWORDS: microvascular angina, peripheral arterial tonometry, endothelium-dependent vasodilation, positron emission tomography. FOR CITATION: Leonova I.A., Zakharova O.V., Boldueva S.A. Disorders of endothelium-dependent vasodilation in patients with microvascular angina. Russian Medical Inquiry. 2022;6(8):427–432 (in Russ.). DOI: 10.32364/2587-6821-2022-6-8-427-432.

PROGNOSTIC VALUE OF PET MPI MYOCARDIAL FLOW RESERVE IN CABG PATIENTS

<h3>BACKGROUND</h3> Positron emission tomography (PET) myocardial perfusion imaging (MPI) is a well-validated non-invasive imaging technique for the assessment of coronary artery disease (CAD). Amongst its many advantage, it permits quantitative, non-invasive assessment of myocardial blood flow (MBF) and myocardial flow reserve (MFR). While the diagnostic and prognostic value of MFR has been extensively validated in the general CAD population, only limited data is available when it comes to its prognostic value in patients with prior coronary artery bypass grafting (CABG). Our study aim was to evaluate if diminished MFR on 13N-Ammonia PET MPI is associated with increased risk of major adverse cardiovascular events (MACE) amongst patients with prior CABG. <h3>METHODS AND RESULTS</h3> A retrospective study was performed at the Montréal University Hospital Centre (CHUM) between February 2018 and September 2020. Patients (n=62) with prior CABG (at least 3 months) who had an 13N-Ammonia PET/CT scan performed were included. The main endpoint was to evaluate if myocardial perfusion values were associated with increased risk of MACE. MACE was defined as death, re-infarction, repeat revascularization or hospitalization for heart failure. In patients with multiple MACE, only the first event was considered for analysis. Our cohort was subdivided in two groups: patients with MACE and patients without MACE. The main indications for performing PET MPI are displayed in the figure. Baseline characteristics (table) were comparable between both groups except for the number of graft (3.0 [2.0,3.0] vs. 3.0 [3.0,4.0], p=0.005). Risk factors were similar between both groups except for presence of chronic kidney disease (CKD) (11 (55%) vs. 10 (23.8%), p=0.02). There was no difference between both groups regarding drug regimen. In patients with MACE as compared to no-MACE, both global MFR (1.8 ± 0.5 vs. 2.1 ± 0.5, p=0.03, respectively) and the global stress MBF (1.2 [0.9,1.4] vs. 1.4 [1.1,1.8] mL/min/g, p=0.049, respectively) were significantly lower. Sum Stress Score was higher in the MACE group (2.5 [1.0,10.0] vs. 0.0 [0.0,3.5], p=0.04). Low left ventricular ejection fraction (LVEF) reserve had no prognostic value in our study (p=0.20). <h3>CONCLUSION</h3> In patients with prior CABG, both reduced global MFR and global stress MBF were associated with increased risk of MACE. Therefore, PET MPI with flow quantification can help identifying patients at risk of MACE after CABG. Our findings need to be confirmed in a larger cohort of patients.

Reducing radiation dose from myocardial perfusion imaging in subjects with complex congenital heart disease

IntroductionThe prevalence of defects and effective radiation dose from various myocardial perfusion imaging (MPI) strategies in congenital heart disease (CHD) is unknown. MethodsWe studied 75 subjects with complex CHD (ages 5 to 80 years) referred for MPI between 2002 and 2015. A rest and exercise or pharmacologic stress MPI was performed using 99mTechnetium sestamibi, 82rubidium or 13N-ammonia, and Sodium iodide SPECT (single-photon emission computed tomography), SPECT/CT or Cadmium zinc telluride (CZT) SPECT or PET (positron emission tomography)/CT scanners. Deidentified images were interpreted semi-quantitatively in three batches: stress only MPI, stress/rest MPI, and stress/rest MPI with taking into account a history of ventricular septal defect repair. Effective radiation dose was estimated for stress/rest MPI and predicted for 1-day stress-first (normal stress scans), and for 2-day stress/rest MPI (abnormal stress scans). ResultsThe median age was 18.6 years. The most common type of CHD was transposition of the great arteries (63%). Rest/stress MPI was abnormal in 43% of subjects and 25% of the abnormal scans demonstrated reversible defects. Of the subjects with abnormal MPI, 33% had significant underlying anatomic coronary artery obstruction. Estimated mean effective radiation dose ranged from 2.1 ± 0.6 mSv for 13N-ammonia PET/CT to 12.5 ± 0.9 mSv for SPECT/CT. Predicted effective radiation dose was significantly lower for stress-first MPI and for 2-day stress/rest protocols. ConclusionsDue to the relatively high prevalence of abnormal stress MPI, tailored protocols with a stress-first MPI as well as the use of 2-day protocols and advanced imaging technologies including CZT SPECT, novel image reconstruction software, and PET MPI could substantially reduce radiation dose in complex CHD.

The prognostic role of PET myocardial perfusion imaging in patients with cardiac sarcoidosis: a systematic review

Abstract Funding Acknowledgements Type of funding sources: None. Background Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac Sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. 18Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. Purpose The aim of this review is to summarize evidence on the prognostic role of FDG PET. Methods Studies were identified by searching MEDLINE from inception to October 2020. Medical Subject Headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done. Results A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported Major Adverse Cardiovascular Events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used Left Ventricular Ejection Fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake. Conclusion Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study

BackgroundDetection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. Methods and resultsAmong 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). ConclusionsAmong symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging

BackgroundPositron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI. MethodsThe primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial’s design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA. ConclusionsThis second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD. Trial Registration Number:NCT03354273

Prognostic value of coronary flow reserve in patients with suspected or known coronary artery disease referred to PET myocardial perfusion imaging: A meta-analysis

BackgroundWe performed a meta-meta-analysis to evaluate the prognostic value of coronary flow reserve (CFR) assessed by cardiac positron emission tomography (PET) imaging in patients with suspected or known coronary artery disease (CAD). MethodsStudies published until April 2019 were identified by database search. We included studies if they evaluated CFR by PET providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. Annualized event rates were calculated and the incidence rate ratios with 95% confidence interval (CI) were estimated to compare patients with impaired and preserved CFR. ResultsWe identified 13 eligible articles including 11,867 patients with a follow-up ranging from 0.6 to 7.1 years. The HR for the occurrence of major adverse cardiac events (MACE) was reported in 11 studies and pooled HR was 1.93 (95% CI 1.65-2.27). The HR for the occurrence of hard events was reported in 5 studies and pooled HR was 3.11 (95% CI 1.88-5.14). Six studies reported data useful to calculate separately the incidence rate of MACE in patients with preserved and impaired CFR and pooled IRR was 2.26 (CI 95% 1.79-2.85). Three studies reported data useful to calculate separately the incidence rate of hard events in patients with preserved and impaired CFR and pooled IRR was 4.12 (CI 95% 3.08-5.51). At meta-regression analysis, we found an association between HR for MACE and gender, diabetes and hypertension, while no significant association was found between HR for hard events and demographic and clinical variables. ConclusionIn patients with suspected or known CAD, an impaired CFR is associated with adverse cardiovascular events. However, the large heterogeneity in study population underlines the need for further investigations to maximize the prognostic role of CFR.

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging

ObjectiveVisually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)–myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the...

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI). BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD. MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables. ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.) ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.

Phase I clinical study of NMB58, a novel positron emission tomography (PET)-myocardial perfusion imaging tracer, conducted to evaluate its safety and pharmacokinetics in Japanese healthy adult males.

NMB58 is a novel positron emission tomography (PET) tracer containing flurpiridaz as an active ingredient and available as a myocardial perfusion imaging tracer that targets mitochondrial complex 1. A phase I clinical study of NMB58 was conducted to evaluate its safety and pharmacokinetics in healthy volunteers. Ten healthy Japanese volunteers received bolus injection of NMB58 (111-167MBq) intravenously and underwent imaging studies at rest on day 1. Of these subjects, 5 (day 2 cohort 1; exercise stress) and 5 (day 2 cohort 2; pharmacological stress) similarly underwent stress imaging studies on day 2. The safety of NMB58 was evaluated through monitoring of signs/symptoms, electrocardiography, vital signs, and laboratory examinations at baseline and several time points during 3days. Sequential whole-body positron emission tomography-computed tomography (PET/CT) scan data were acquired for up to 5-h post-injection, with venous blood and urine samples collected for up to 8-h post-injection. Based on the results of the biodistribution study, the absorbed radiation dose (Rad) was estimated by the Medical Internal Radiation Dose method. On day 1, the kidneys were shown to have the highest Rad, followed by the myocardium. On day 2, the myocardium was shown to have the highest Rad, followed by the kidneys. The mean effective doses (EDs) per unit activity administered were 0.021, 0.017 and 0.021mSv/MBq for overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2, respectively. The estimated exposure dose of NMB58 was similar to or lower than those of radiotracers currently approved for clinical use, including 18F-Fludeoxyglucose. Biodistribution results indicated that NMB58 distributed to the myocardium exhibited high and sustained retention after administration. The cumulative urinary radioactivity excretion rate was shown to be 6.9, 2.3%, and 8.0% of the injected dose in overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. Based on radiation dosimetry, biodistribution, and safety evaluations, NMB58 was found to be a suitable tracer for clinical use in PET myocardial perfusion imaging during exercise or pharmacological stress.

CCTA-derived functional and morphological features and their comparative performance in predicting impaired coronary vasodilatation by PET-myocardial perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 onbehalf EVINCI-SMARTOOL Background/Objectives: The relationship between biomechanical characteristics of a coronary lesion with myocardial blood flow has not been studied. We investigated the relationship between local endothelial shear stress (ESS) and computed tomography coronary angiography (CTCA)-derived anatomical and plaque characteristics data with impaired vasodilating capability assessed by positron emission tomography myocardial perfusion imaging (PET-MPI). Methods A total of 92 coronary vessels of 53 patients who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia were analysed. PET was considered abnormal when &amp;gt; 1 contiguous segments showed both stress Myocardial Blood Flow (MBF) ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or &amp;lt;1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. CTCA images were used to assess stenosis severity, lesion specific total plaque volume (PV), non-calcified PV and calcified PV as well as plaque phenotype. ESS was calculated for the full length of a lesion (total), as well as in the proximal, minimum lumen area and distal lesion segments. Results ESS was weakly correlated with total PV (rho = 0.273, p = 0.008), non-calcified PV (rho = 0.247, p = 0.017) and the volume of necrotic core (rho = 0.242, p = 0.02). ESS increased progressively with stenosis severity (p ≤ 0.001). ΕSS was also higher in functionally significant vs. non-significant lesions (10.4 [8.04-54.4] Pa vs. 3.9 [2.32-7.29] Pa, p ≤0.001). Addition of ESS to stenosis severity improved prediction (Δ[AUC]:0.113, 95% CI: 0.055 to 0.171, p = 0.0001) of functionally significant lesions. Conclusion There is a weak positive association between lesion-specific ESS and plaque volume. ESS increases progressively with stenosis severity and is higher in functionally significant lesions by PET-MPI. The addition of ESS to CTCA-anatomical information improves prediction of an abnormal PET-MPI result.

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis\u2014validation against 13N-ammonia positron emission tomography

ObjectivesCoronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI).MethodsSixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell’s c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%).ResultsCAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82–0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively).ConclusionsCAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone.Key Points• Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from13N-ammonia positron emission tomography myocardial perfusion imaging.• CAVi is independently associated with abnormal stress myocardial blood flow.• CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR\xa0scanner

BackgroundInadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET).MethodsWe prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMRstress) and rest.ResultsSixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRstress were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMRstress: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMRstress and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004).ConclusionsThe presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.

Abstract 14953: Temporal Trends in Non-invasive Diagnostic Tests for Ischemic Heart Disease Among Us Adults Age 64 Years or Younger: Results From the Marketscan Survey, 2010-2018

Introduction: Heart disease is the leading cause of death in the U.S. Ischemic heart disease (IHD) accounts for two thirds of heart disease deaths. Non-invasive cardiovascular tests (NITs) are often the first step to establish an IHD diagnosis. Methods: We analyzed 2010-2018 IBM® MarketScan® Commercial Databases. NITs including exercise ECG, stress echocardiography, CT coronary artery calcification score (CT-CAC), single-photon emission computerized tomography (SPECT), cardiac CT angiography (CTA), nuclear positron emission tomography/myocardial perfusion imaging (PET/MPI), stress MRI, were identified using current procedural terminology (CPT) codes. IHD using ICD 9/10 codes (410-414, 429.2/I20-I25) and chest pain (786.59/R07.89) or unspecified chest pain (786.50/R07.9) were identified. The 2000 Census population was used to calculate the age standardized prevalence. Results: The data included 20,726,587 individuals (48.1% men, mean age (standard deviation) of 49.1 (13.5) years), among which 67,339 had a diagnosis of IHD or chest pain in 2018. The age standardized prevalence of the overall population that had at least one of the 7 tests is 1.60% in 2018, down from 2.47% in 2010. The responding prevalence for those with IHD or chest pain was 54.3% in 2018 and 61.6% in 2010. Exercise ECG was the most utilized test for the overall population: 0.94% in 2018 down from 1.31% in 2010; SPECT was second most often used with 0.75% in 2018 and 1.24% in 2010. However, SPECT was the most often utilized test among those with CHD or chest pain: 38.2% in 2018, down from 45.0% in 2010, and exercise ECG second most often with 32.6% in 2018 and 34.9% in 2010. An increase in use of CT-CAC, PET/MPI, and CTA tests was observed since 2010, but the prevalence of all were low in 2018. 0.02%. 0.01%, and 0.04% for the overall population and 0.20%, 0.95% and 3.20% for those with IHD or chest pain, respectively. Conclusions: Almost 2% of the general younger US adult population and over half of those with IHD or chest pain had undergone at least one of 7 NITs in 2018. While the utilization of overall NITs for both the general population and those with IHD or chest pain has declined since 2010, it has increased for CT-CAC, PET/MPI, and CTA but still less than 1% for CT-CAC and PET/MPI..

Effect of proton pump inhibitors on Rubidium-82 gastric uptake using positron emission tomography myocardial perfusion imaging

BackgroundRb-82 positron emission tomography (PET) myocardial perfusion imaging (MPI) is a robust tool for the evaluation of coronary artery disease (CAD). However, gastric uptake and spillover can be seen in 10% of Rb-82 PET MPI studies, commonly affecting the inferior wall, and can preclude the accurate identification of myocardial ischemia. We sought to understand the relationship between Rb-82 gastric uptake and the use of proton pump inhibitors (PPI). Methods600 consecutive patients who presented for a clinically indicated Rb-82 PET MPI study were prospectively enrolled. In addition to the clinical history, PPI use was ascertained (medication, dose, frequency and duration of use, and time of last dose). Patients were categorized as PPI and non-PPI users. Rb-82 uptake in the gastrium, myocardium, and liver were measured at rest. Absolute uptake values and gastric:hepatic ratios were compared in PPI and non-PPI users. ResultOf 600 enrolled patients, 181 (30.2%) patients were using PPI. The gastric Rb-82 uptake in PPI users was 23% higher than non-PPI users (146 ± 52 kBq/cc vs 119 ± 40 kBq/cc, respectively; P < 0.001). The resting gastric:hepatic Rb-82 uptake ratio was also 23% higher in PPI vs non-PPI users (2.7 ± 1.0 vs 2.2 ± 0.8, respectively; P < 0.001). ConclusionThe gastric uptake of Rb-82 appears to be greater in patients actively using PPI and may identify a group who might be at greater risk of non-diagnostic Rb-82 PET MPI.

Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease

BackgroundFluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. ObjectivesThis study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m–labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated. MethodsIn this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data. ResultsSensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated. ConclusionsFlurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710)

P250 Evaluation of coronary endothelial dysfunction by positron emission tomography: does gender make a difference

Abstract Funding Acknowledgements None Introduction Endothelial dysfunction (ED) manifested as abnormality of coronary microvasculature is associated with poor prognosis in patients presenting with chest pain. ED can be noninvasively evaluated by assessment of coronary flow reserve with positron emission tomography (PET). Studies directly comparing ED in men and women are limited. The aim of this study is to compare gender differences in ED as measured by CFR on PET myocardial perfusion imaging. Methods All the consecutive patients referred to PET-MPI between May 2011 and June 2018 were reviewed. Patient without known CAD who had normal perfusion were included in the analysis. Patient with abnormal electrocardiogram, significant transient ischemic dilatation, low left ventricular ejection fraction and high calcium score (&amp;gt;1000 AU) and renal failure were excluded. CFR is calculated as the ratio of stress/rest myocardial blood flow. CFR &amp;lt; 2 was considered as abnormal indicating the presence of ED. Results 1711 patients were included in the analysis (mean age 60.2 ± 10 year, 68% females). Females were older and had higher BMI and diabetes (DM). Both resting and peak myocardial blood flow (MBF) was higher in females (1.16 vs 1.02 (p &amp;lt; 0.0001)) and 3.26 vs 2.9 (p &amp;lt; 0.001)0 respectively. Around 68% of males had abnormal CFR (&amp;lt;2) compared to 63% of females (p = 0.05). After adjusting for the confounders, female gender was associated with higher peak MBF (Hazard ratio 0.29, 95% CI 0.19 –0.40, p &amp;lt; 0.001) and lower chance of having ED (Hazard ratio -0.15, 95% CI -0.29 - -0.005, p = 0.049) Conclusions Endothelial dysfunction as measured noninvasively by CFR on PET is prevalent among both sexes. Higher level of peak MBF in females may call for a different cut-off for abnormal CFR in women. Outcome studies are required to evaluate the clinical utility and prognostic value of such a cut-off.

1172 Predictive value of coronary artery calcium score for myocardial ischaemia in positron emission tomography

Abstract Funding Acknowledgements This study received no funding. Introduction Coronary artery calcium score (CACS) is an excellent predictor of long-term adverse cardiac events. However, little is known about its value and thresholds for immediate prediction of myocardial ischaemia. Purpose We tested the ability of CACS to predict myocardial ischaemia in patients with positron emission tomography (PET). In particular, we assessed the negative predictive value (NPV) of low CACS and the positive predictive value (PPV) of high CACS for myocardial ischaemia. Methods All consecutive patients undergoing 82Rb PET myocardial perfusion imaging with CACS from October 2016 to January 2019 at our centre were enrolled. Patients with known coronary artery disease (CAD) were excluded. Ischaemia was defined as a summed difference score (SDS) ≥4 in PET, and severe ischaemia as SDS ≥8 or transient ischaemic dilation. CACS was measured from low-dose computed tomography (CT) scans using the Agatston method. Receiver operating characteristic (ROC) analysis was used to calculate areas under the curves (AUC, with 95% confidence interval) and to assess sensitivity, specificity, PPV and NPV of CACS for ischaemia at pre-specified cut-offs (0, 100, 400, and 1000 Agatston units [AU]). Multivariate logistic regression was used to assess the predictive ability of CACS with clinical and ECG data, using odds ratios (OR, with 95% confidence interval). Prediction models were generated with propensity scores for CACS and clinical data with ECG, and compared using AUC. Results Of 1833 patients, 927 were included, all with CACS and 82Rb PET, without known CAD. Mean age was 64.3 ±11.1 years and median CACS was 55 AU (interquartile range 359). In PET, 179 patients (19.3%) had ischaemia and 87 (9.4%) severe ischaemia. To predict ischaemia, CACS had an AUC of 0.82 (0.79-0.84) and was superior to the clinical and ECG data model (AUC 0.68 [0.65-0.71], P &amp;lt; 0.0001 vs. CACS, Figure 1). For ischaemia, CACS 0 AU had 97% sensitivity and 98% NPV, and CACS 100 AU 81% sensitivity and 94% NPV. But CACS 1000 AU had 94% specificity and 60% PPV. Results were similar for severe ischaemia, with an AUC of 0.81 for CACS (0.79-0.84) and superiority over the clinical and ECG data model (AUC 0.74 [0.71-0.77], P = 0.018 vs. CACS). For severe ischaemia, CACS 0 AU had 98% sensitivity and 99% NPV, and CACS 100 AU 85% sensitivity and 98% NPV. But CACS 1000 AU had 90% specificity and 30% PPV. In multivariate analysis, CACS was the strongest predictor of ischaemia (OR 1.14 [1.11-1.17] by 100 AU, P &amp;lt; 0.0001) and made all clinical and ECG data nonsignificant. Conclusion CACS is a valuable predictor of myocardial ischaemia in PET. In particular, CACS ≤100 AU has an excellent NPV and CACS ≥1000 a good PPV for myocardial ischaemia. These findings can be useful to assess the need for additional cardiac testing after a chest CT showing coronary calcifications and to support the interpretation of borderline myocardial perfusion results. Abstract 1172 Figure 1: Prediction of ischaemia