Combined use of PET perfusion imaging and coronary computed tomography angiography in evaluation of stable coronary artery disease

Coronary computed tomography angiography (CTA) enables non-invasive detection of coronary atherosclerotic plaques. In turn, myocardial perfusion imaging (MPI) using positron emission tomography (PET) allows non-invasive measurement of myocardial blood flow. Hybrid imaging refers to combining data from two different imaging modalities. Anatomical information from CTA and functional information from MPI are potentially complementary in evaluation of coronary artery disease (CAD). However, the clinical benefit and optimal use of cardiac hybrid imaging are unclear. We investigated the selective combined use coronary CTA and PET MPI in evaluation of stable symptomatic patients with suspected CAD. Patients first underwent coronary CTA to detect coronary stenoses, and those patients who presented with a suspected obstructive stenosis on CTA also underwent PET MPI to study the hemodynamic significance of the stenosis. We found that obstructive CAD could be ruled out by coronary CTA alone in about half of the patients, associated with an excellent prognosis. Instead, reduced myocardial PET perfusion was associated with an impaired outcome. Renal injury is a potential complication of iodine contrast agents. We found a low incidence of persistent renal dysfunction after coronary CTA in stable patients with suspected CAD. We also studied an integrated risk score derived from CTA findings, and found this score to predict future adverse events in patients with suspected CAD. Finally, we assessed hybrid PET/CTA findings in symptomatic patients with previous coronary artery bypass grafting. The integrative assessment allowed the evaluation of myocardial perfusion defects and their co-localization with the supplying coronary arteries or bypass grafts.PET-perfuusiokuvantamisen ja sepelvaltimoiden tietokonetomografian yhteiskäyttö vakaaoireisen sepelvaltimotaudin arvioinnissa. Sepelvaltimoiden tietokonetomografialla (TT) voidaan havaita sepelvaltimoiden ateroskleroottiset plakit kajoamattomasti. Positroniemissiotomografia (PET) puolestaan mahdollistaa sydänlihaksen verenvirtauksen eli perfuusion mittaamisen. Hybridi- eli yhdistelmäkuvantamisella tarkoitetaan kahdella eri kuvantamismenetelmällä saadun tiedon yhdistämistä. TT-tutkimuksen antama tieto sepelvaltimoiden anatomiasta ja PET-kuvantamisen tarjoama toiminnallinen tieto voivat täydentää toisiaan sepelvaltimotaudin arvioinnissa. On kuitenkin epäselvää, mikä on sydämen yhdistelmäkuvantamisen kliininen hyöty ja paras tapa soveltaa sitä käytännössä. Tutkimme sepelvaltimoiden TT-kuvantamisen ja sydänlihaksen PET-perfuusiokuvantamisen valikoitua yhteiskäyttöä vakaaoireisilla potilailla, joilla epäiltiin sepelvaltimotautia. Potilaille tehtiin ensin sepelvaltimoiden TT-tutkimus sepelvaltimoahtaumien havaitsemiseksi, ja mikäli TT-tutkimuksessa todettiin epäily merkittävästä sepelvaltimoahtaumasta, tehtiin lisäksi PET-perfuusiokuvaus ahtauman merkittävyyden tarkemmaksi arvioimiseksi. Havaitsimme, että noin puolella potilaista ahtauttava sepelvaltimotauti voitiin poissulkea pelkän TT-tutkimuksen perusteella, ja näillä potilailla ennuste oli erinomainen. Sen sijaan alentunut sydänlihasperfuusio PET-tutkimuksessa oli yhteydessä heikentyneeseen ennusteeseen. Munuaisvaurio on mahdollinen jodivarjoaineiden käytön haittavaikutus. Havaitsimme, että pysyvä munuaisten toimintahäiriö oli harvinainen vakaaoireisilla potilailla, joille tehtiin sepelvaltimoiden TT-tutkimus epäillyn sepelvaltimotaudin vuoksi. Tutkimme myös sepelvaltimoiden TTlöydöksistä johdettua riskipisteytystä ja havaitsimme sen ennustavan tulevia haittatapahtumia potilailla, joilla epäiltiin sepelvaltimotautia. Lopuksi analysoimme PET/TT-kuvantamislöydöksiä oireisilla potilailla, joille oli aiemmin tehty sepelvaltimoiden ohitusleikkaus. Yhdistelmäkuvantamisella voitiin arvioida sydänlihaksen perfuusiopuutoksia ja paikantaa ne suhteessa yksilölliseen sepelvaltimoiden ja ohitteiden kulkuun

Cardiac perfusion by positron emission tomography

Myocardial perfusion imaging (MPI) with positron emission tomography (PET) is an established tool for evaluation of obstructive coronary artery disease (CAD). The contemporary 3-dimensional scanner technology and the state-of-the-art MPI radionuclide tracers and pharmacological stress agents, as well as the cutting-edge image reconstruction techniques and data analysis software, have all enabled accurate, reliable and reproducible quantification of absolute myocardial blood flow (MBF), and henceforth calculation of myocardial flow reserve (MFR) in several clinical scenarios. In patients with suspected coronary artery disease, both absolute stress MBF and MFR can identify myocardial territories subtended by epicardial coronary arteries with haemodynamically significant stenosis, as defined by invasive coronary fractional flow reserve measurement. In particular, absolute stress MBF and MFR offered incremental prognostic information for predicting adverse cardiac outcome, and hence for better patient risk stratification, over those provided by traditional clinical risk predictors. This article reviews the available evidence to support the translation of the current techniques and technologies into a useful decision-making tool in real-world clinical practice

Improving patient identification for advanced cardiac imaging through machine learning-integration of clinical and coronary CT angiography data

Background: Standard computed tomography angiography (CTA) outputs a myriad of interrelated variables in the evaluation of suspected coronary artery disease (CAD). But an important proportion of obstructive lesions does not cause significant myocardial ischemia. Nowadays, machine learning (ML) allows integration of numerous variables through complex interdependencies that optimize classification and prediction at the individual level. We evaluated ML performance in integrating CTA and clinical variables to identify patients that demonstrate myocardial ischemia through PET and those who ultimately underwent early revascularization. Methods and results: 830 patients with CTA and selective PET were analyzed. Nine clinical and 58 CTA variables were integrated through ensemble-boosting ML to identify patients with ischemia and those who underwent early revascularization. ML performance was compared against expert CTA interpretation, calcium score and clinical variables. While ML using all CTA variables achieved an AUC = 0.85, it was outperformed by expert CTA interpretation (AUC = 0.87, p < 0.01 for comparison), comparable to ML integration of CTA variables with clinical variables. However, the best performance was achieved by ML integration of expert CTA interpretation and clinical variables for both dependent variables (AUCs = 0.91 and 0.90, p < 0.001). Conclusions: Machine learning integration of diagnostic CTA and clinical data may improve identification of patients with myocardial ischemia and those requiring early revascularization at the individual level. This could potentially aid in sparing the need for subsequent advanced imaging and better identifying patients in ultimate need for revascularization. While ML integrating all CTA variables did not outperform expert CTA interpretation, ML data integration from different sources consistently improves diagnostic performance. (C) 2021 The Authors. Published by Elsevier B.V

Global and segmental absolute stress myocardial blood flow in prediction of cardiac events: [15O] water positron emission tomography study

Purpose We evaluated the value of reduced global and segmental absolute stress myocardial blood flow (sMBF) quantified by [O-15] water positron emission tomography (PET) for predicting cardiac events in patients with suspected obstructive coronary artery disease (CAD). Methods Global and segmental sMBF during adenosine stress were retrospectively quantified in 530 symptomatic patients who underwent [O-15] water PET for evaluation of coronary stenosis detected by coronary computed tomography angiography. Results Cardiovascular death, myocardial infarction, or unstable angina occurred in 28 (5.3%) patients at a 4-year follow-up. Reduced global sMBF was associated with events (area under the receiver operating characteristic curve 0.622, 95% confidence interval (95% CI) 0.538-0.707, p = 0.006). Reduced global sMBF (< 2.2 ml/g/min) was found in 22.8%, preserved global sMBF despite segmentally reduced sMBF in 35.3%, and normal sMBF in 41.9% of patients. Compared with normal sMBF, reduced global sMBF was associated with the highest risk of events (adjusted hazard ratio (HR) 6.970, 95% CI 2.271-21.396, p = 0.001), whereas segmentally reduced sMBF combined with preserved global MBF predicted an intermediate risk (adjusted HR 3.251, 95% CI 1.030-10.257, p = 0.044). The addition of global or segmental reduction of sMBF to clinical risk factors improved risk prediction (net reclassification index 0.498, 95% CI 0.118-0.879, p = 0.010, and 0.583, 95% CI 0.203-0.963, p = 0.002, respectively). Conclusion In symptomatic patients evaluated for suspected obstructive CAD, reduced global sMBF by [O-15] water PET identifies those at the highest risk of adverse cardiac events, whereas segmental reduction of sMBF with preserved global sMBF is associated with an intermediate event risk

Improving patient identification for advanced cardiac imaging through machine learning-integration of clinical and coronary CT angiography data

BackgroundStandard computed tomography angiography (CTA) outputs a myriad of interrelated variables in the evaluation of suspected coronary artery disease (CAD). But an important proportion of obstructive lesions does not cause significant myocardial ischemia. Nowadays, machine learning (ML) allows integration of numerous variables through complex interdependencies that optimize classification and prediction at the individual level. We evaluated ML performance in integrating CTA and clinical variables to identify patients that demonstrate myocardial ischemia through PET and those who ultimately underwent early revascularization.Methods and results830 patients with CTA and selective PET were analyzed. Nine clinical and 58 CTA variables were integrated through ensemble-boosting ML to identify patients with ischemia and those who underwent early revascularization. ML performance was compared against expert CTA interpretation, calcium score and clinical variables. While ML using all CTA variables achieved an AUC = 0.85, it was outperformed by expert CTA interpretation (AUC = 0.87, p ConclusionsMachine learning integration of diagnostic CTA and clinical data may improve identification of patients with myocardial ischemia and those requiring early revascularization at the individual level. This could potentially aid in sparing the need for subsequent advanced imaging and better identifying patients in ultimate need for revascularization. While ML integrating all CTA variables did not outperform expert CTA interpretation, ML data integration from different sources consistently improves diagnostic performance.</p

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging

BackgroundAdditional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD.Methods and resultsSymptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P P ConclusionsAdding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD. </p

Time-resolved fluorescence based direct two-site apoA-I immunoassays and their clinical application in patients with suspected obstructive coronary artery disease

Objective: High-density lipoprotein (HDL) is a heterogeneous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of assays that can target the functionality of HDL particles related to atherosclerosis. The objective of this study was to construct two-site apolipoprotein A-I (apoA-I) assays and to evaluate their clinical performance in patients with suspected obstructive coronary artery disease (CAD).Approach and results: Direct two-site apoA-I assays (named 109–121 and 110–525) were developed to identify the presence of apoA-I in the HDL of patients with CAD using apoA-I antibodies as a single-chain variable fragment fused with alkaline phosphatase. ApoA-I109−121 and apoA-I110−525 were measured in 197 patients undergoing coronary computed tomography angiography (CTA) and myocardial positron emission tomography perfusion imaging due to suspected obstructive CAD. Among patients not using lipid-lowering medication (LLM, n = 125), the level of apoA-I110−525 was higher in the presence than in the absence of coronary atherosclerosis [21.88 (15.89–27.44) mg/dl vs. 17.66 (13.38–24.48) mg/dl, P = 0.01)], whereas there was no difference in apoA-I109−121, HDL cholesterol, and apoA-I determined using a polyclonal apoA-I antibody. The levels of apoA-I109−121 and apoA-I110−525 were similar in the presence or absence of obstructive CAD. Among patients not using LLM, apoA-I110−525 adjusted for age and sex identified individuals with coronary atherosclerosis with a similar accuracy to traditional risk factors [area under the curve [AUC] (95% CI): 0.75(0.66–0.84) 0.71 (0.62–0.81)]. However, a combination of apoA-I110−525 with risk factors did not improve the accuracy [AUC (95% CI): 0.73 (0.64–0.82)].Conclusion: Direct two-site apoA-I assays recognizing heterogeneity in reactivity with apoA-I could provide a potential approach to identify individuals at a risk of coronary atherosclerosis. However, their clinical value remains to be studied in larger cohorts.</p

Coronary computed tomography angiography-based endothelial wall shear stress in normal coronary arteries

Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments. Factors potentially affecting ESS values were examined, including sex, lumen diameter and distance from the ostium. Segments were categorized according to lumen diameter tertiles into small (= 3.2 mm) segments. A total of 349 normal vessels from 168 patients (mean age 59 +/- 9 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex artery and right coronary artery (minimal ESS 2.3 Pa vs. 1.9 Pa vs. 1.6 Pa, p < 0.001 and maximal ESS 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa, p < 0.001). Men had lower ESS values than women, also after adjusting for lumen diameter (p < 0.001). ESS values were highest in small segments compared to intermediate or large segments (minimal ESS 3.8 Pa vs. 1.7 Pa vs. 1.2 Pa, p < 0.001 and maximal ESS 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa, p < 0.001). A weak to strong correlation was found between ESS and distance from the ostium (rho = 0.22-0.62, p < 0.001). CCTA-based ESS values increase rapidly and become widely scattered with decreasing lumen diameter. This needs to be taken into account when assessing the added value of ESS beyond lumen diameter in highly stenotic lesions

Functional stress imaging to predict abnormal coronary fractional flow reserve: the PACIFIC 2 study

AimsThe diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI).Methods and resultsIn this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P = 0.03) and MRI (64%, 57–72%, P = 0.052). Using FFR ConclusionIn this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.</p

Sepelvaltimotaudin kajoamaton yhdistelmäkuvantaminen löydösten yhteys ennusteeseen

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