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1. Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography

Author

Kwiecinski, Jacek, Wang, Kang-Ling, Tzolos, Evangelos, Moss, Alastair, Daghem, Marwa, Adamson, Philip D., Dey, Damini, Molek-Dziadosz, Patrycja, Dawson, Dana, Arumugam, Parthiban, Sabharwal, Nikant, Greenwood, John P., Townend, John N., Calvert, Patrick A., Rudd, James HF., Berman, Daniel, Verjans, Johan W., Williams, Michelle C., Slomka, Piotr, Dweck, Marc R., and Newby, David E.

Published
2024
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2. Qualitative and quantitative analysis of 18F-GP1 positron emission tomography in thrombotic cardiovascular disease

Author

Whittington, Beth, Tzolos, Evangelos, Joshi, Shruti, Bing, Rong, Andrews, Jack, Loganath, Krithika, Craig, Neil, Balmforth, Craig, Clark, Laura, Lucatelli, Christophe, MacAskill, Mark G, Tavares, Adriana A. S., Clark, Tim, Mills, Nicholas L., Nash, Jennifer, Dey, Damini, Slomka, Piotr J., Koglin, Norman, Stephens, Andrew W., Dweck, Marc R., Williams, Michelle C., Whiteley, William, van Beek, Edwin J. R., Wardlaw, Joanna M., and Newby, David E.

Published
2024
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3. First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Author

Andrews, Jack P. M., Joshi, Shruti S., Tzolos, Evangelos, Syed, Maaz B., Cuthbert, Hayley, Crica, Livia E., Lozano, Neus, Okwelogu, Emmanuel, Raftis, Jennifer B., Bruce, Lorraine, Poland, Craig A., Duffin, Rodger, Fokkens, Paul H. B., Boere, A. John F., Leseman, Daan L. A. C., Megson, Ian L., Whitfield, Phil D., Ziegler, Kerstin, Tammireddy, Seshu, Hadjidemetriou, Marilena, Bussy, Cyrill, Cassee, Flemming R., Newby, David E., Kostarelos, Kostas, and Miller, Mark R.

Published
2024
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4. Aortic valve imaging using 18F-sodium fluoride: impact of triple motion correction

Author

Lassen, Martin Lyngby, Tzolos, Evangelos, Massera, Daniele, Cadet, Sebastien, Bing, Rong, Kwiecinski, Jacek, Dey, Damini, Berman, Daniel S, Dweck, Marc R, Newby, David E, and Slomka, Piotr J

Subjects
Medical and Biological Physics, Biomedical and Clinical Sciences, Clinical Sciences, Physical Sciences, Cardiovascular, Bioengineering, Heart Disease, Biomedical Imaging, Clinical Research, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Motion correction, PET/CT, Cardiac PET, F-18-sodium fluoride, Aortic valve imaging, 18F-sodium fluoride, Clinical sciences, Biomedical engineering, Medical and biological physics
Abstract

BackgroundCurrent 18F-NaF assessments of aortic valve microcalcification using 18F-NaF PET/CT are based on evaluations of end-diastolic or cardiac motion-corrected (ECG-MC) images, which are affected by both patient and respiratory motion. We aimed to test the impact of employing a triple motion correction technique (3 × MC), including cardiorespiratory and gross patient motion, on quantitative and qualitative measurements.Materials and methodsFourteen patients with aortic stenosis underwent two repeat 30-min PET aortic valve scans within (29 ± 24) days. We considered three different image reconstruction protocols; an end-diastolic reconstruction protocol (standard) utilizing 25% of the acquired data, an ECG-gated (four ECG gates) reconstruction (ECG-MC), and a triple motion-corrected (3 × MC) dataset which corrects for both cardiorespiratory and patient motion. All datasets were compared to aortic valve calcification scores (AVCS), using the Agatston method, obtained from CT scans using correlation plots. We report SUVmax values measured in the aortic valve and maximum target-to-background ratios (TBRmax) values after correcting for blood pool activity.ResultsCompared to standard and ECG-MC reconstructions, increases in both SUVmax and TBRmax were observed following 3 × MC (SUVmax: Standard = 2.8 ± 0.7, ECG-MC = 2.6 ± 0.6, and 3 × MC = 3.3 ± 0.9; TBRmax: Standard = 2.7 ± 0.7, ECG-MC = 2.5 ± 0.6, and 3 × MC = 3.3 ± 1.2, all p values ≤ 0.05). 3 × MC had improved correlations (R2 value) to the AVCS when compared to the standard methods (SUVmax: Standard = 0.10, ECG-MC = 0.10, and 3 × MC = 0.20; TBRmax: Standard = 0.20, ECG-MC = 0.28, and 3 × MC = 0.46).Conclusion3 × MC improves the correlation between the AVCS and SUVmax and TBRmax and should be considered in PET studies of aortic valves using 18F-NaF.

Published
2022

5. Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis

Author

Lembo, Maria, Joshi, Shruti S., Geers, Jolien, Bing, Rong, Carnevale, Lorenzo, Pawade, Tania A., Doris, Mhairi K., Tzolos, Evangelos, Grodecki, Kajetan, Cadet, Sebastien, Craig, Neil, Singh, Trisha, Slomka, Piotr J., White, Audrey, Guala, Andrea, Rodriguez-Palomares, Jose F., Ruiz-Muñoz, Aroa, Dux-Santoy, Lydia, Teixido-Tura, Gisela, Galian-Gay, Laura, Williams, Michelle C., Newby, David E., Kwak, Soongu, Lee, Seung-Pyo, Powers, Andreanne, Clavel, Marie-Annick, Dey, Damini, and Dweck, Marc R.

Published
2024
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8. Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction

Author

Wang, Kang-Ling, Balmforth, Craig, Meah, Mohammed N., Daghem, Marwa, Moss, Alastair J., Tzolos, Evangelos, Kwiecinski, Jacek, Molek-Dziadosz, Patrycja, Craig, Neil, Bularga, Anda, Adamson, Philip D., Dawson, Dana K., Arumugam, Parthiban, Sabharwal, Nikant K., Greenwood, John P., Townend, Jonathan N., Calvert, Patrick A., Rudd, James H.F., Verjans, Johan W., Berman, Daniel S., Slomka, Piotr J., Dey, Damini, Mills, Nicholas L., van Beek, Edwin J.R., Williams, Michelle C., Dweck, Marc R., and Newby, David E.

Published
2024
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9. Novel positron emission tomography applications for imaging cardiovascular disease activity

Author

Tzolos, Evangelos, Newby, David, and Dweck, Marc

Subjects
616.1, 18F-sodium fluoride, microcalcification, Positron emission tomography, breathing tracing, calcification activity
Abstract

Background: Calcification is one of the body's primary responses to injury and a key pathological feature of cardiovascular disease. Calcification activity can now be imaged using 18F-sodium-fluoride positron emission tomography and computed tomography which targets microcalcification (diameter <50 μm), providing different information to established macroscopic calcification (minimum diameter 200 to 500 μm) imaged with computed tomography. Indeed 18F-sodium fluoride PET has now been explored in a wide range of conditions including coronary atherosclerosis, aortic stenosis and bioprosthetic valve disease, offering a marker of vascular injury and disease activity in each condition studied. At the moment, we lack reliable and reproducible methods for predicting myocardial infarction in patients with established coronary artery disease. Moreover, there remain major uncertainties regarding disease activity within the retained native aortic valve as well as bioprosthetic valve durability following transcatheter aortic valve implantation. In this thesis, I will address the following questions: 1) What is the optimal method for quantifying microcalcification activity and how reproducible is it? 2) Can we further refine it? 3) Can 18F-sodium fluoride PET/CT predict myocardial infarction in patients with advanced atherosclerosis? 4) Can machine learning improve the ability of 18F-sodium fluoride PET/CT to predict events? 5) Can 18F-sodium fluoride PET/CT predict native aortic valve disease progression and bioprosthetic valve degeneration in patients with transcatheter aortic valve implantation? Methods and Results: Study one: 18F-sodium fluoride reproducibility We aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA). Nineteen patients with established coronary artery disease were included for analysis. CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12±5 days apart. We demonstrated that CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA=0) of coronary18F-sodium fluoride uptake. Mean CMA was 3.12± 0.62 with coefficients of repeatability of 0.24 and 0.22 for intraobserver, 0.30 and 0.29 for interobserver and 0.33 and 0.32 for interscan analysis at a per-vessel and per-patient level respectively. Study two: Refining 18F-sodium fluoride uptake We aimed to evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of 18F-sodium fluoride in PET/CT. Twenty-three patients with calcified plaques in the coronary arteries were included. We evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. We demonstrated that respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary 18F-sodium fluoride uptake on PET/CT. Assessments of the individual vessel microcalcification burden (CMA) revealed no major differences between PET images reconstructed using CTAC and RACTAC scans (median [IQR] CMA: CTAC = 0.10 [0-1.0], RACTAC = 0.15 [0-1.03], p=0.19). Bland-Altman plots of the CMA values revealed a high degree of agreement when comparing the per vessel burden, with coefficient of reproducibility of 0.17. Study three: Coronary 18F-sodium fluoride PET/CT In a multicentre study, we investigated whether coronary 18F-sodium fluoride PET uptake predicts future myocardial infarction in patients with established coronary artery disease, and whether it can provide additional prognostic information over and above current methods of risk stratification including clinical risk scores, coronary calcium scoring and the severity of obstructive coronary artery disease. We studied 293 participants (65±9 years; 84% male) with established coronary artery disease. Patients underwent 18F-sodium fluoride PET/CT and were followed-up for fatal or non-fatal myocardial infarction over 42 [31-49] months. Total coronary 18F-sodium fluoride uptake was determined using coronary microcalcification activity (CMA). Fatal or non-fatal myocardial infarction occurred only in patients with increased coronary 18F-sodium fluoride activity (20/203 CMA > 0 versus 0/90 CMA=0; p<0.001). On receiver operator-curve analysis, fatal or non-fatal myocardial infarction prediction was highest for 18F-sodium fluoride CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index, cardiac risk scores (areas under curve: 0.76 versus 0.54, 0.62, 0.52 and 0.54; p<0.001 for all). Patients with CMA > 1.56 had >7-fold increase in fatal or non-fatal myocardial infarction (hazard ratio 7.1, 95% confidence interval 2.2 to 25.1; p=0.003) independent of age, gender, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, cardiac risk scores, the Duke coronary artery disease index and recent myocardial infarction. Study four: Artificial intelligence in 18F-sodium fluoride PET/CT We undertook a post-hoc analysis of the population of patients from study three. Coronary 18F-sodium fluoride PET/CT and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. We demonstrated that our machine learning approach has overcome the challenges posed by co-linearity of these variables and, for the first time, demonstrated that this information is complementary and additive with the combination of both providing the most robust outcome prediction. On univariable receiver-operator-curve analysis, only 18F-sodium fluoride coronary uptake emerged as a predictor of myocardial infarction (c- statistic 0.76, 95% confidence interval [CI] 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76;) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18F-sodium fluoride PET), we achieved a substantial improvement (p=0.008 versus 18F-sodium fluoride PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Study five: 18F-sodium fluoride in transcatheter aortic valves We undertook a multicentre cross-sectional observational cohort study to determine whether the retained native aortic valves in patients undergoing transcatheter aortic valve implantation (TAVI) demonstrate evidence of ongoing disease progression. Additionally, since long-term durability of transcatheter aortic valves is yet to be established, we aimed to establish whether bioprosthetic valve durability or degeneration was appreciably different from patients with surgical aortic valve replacement (SAVR). Patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, CT angiography and 18F-sodium fluoride PET/CT. Subsequently patients underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made to matched patients with bioprosthetic SAVR who had undergone the same imaging protocol. We enrolled 47 patients (81±6 years old, 79% male) with TAVI from 3 high volume centres. We demonstrated that 18F-sodium fluoride uptake within the native aortic valve is higher with longer duration of implantation suggesting disease activity continues despite immobilisation of the valve leaflet.

Published
2022
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10. Bypass Grafting and Native Coronary Artery Disease Activity

Author

Kwiecinski, Jacek, Tzolos, Evangelos, Fletcher, Alexander J, Nash, Jennifer, Meah, Mohammed N, Cadet, Sebastien, Adamson, Philip D, Grodecki, Kajetan, Joshi, Nikhil, Williams, Michelle C, van Beek, Edwin JR, Lai, Chi, Tavares, Adriana AS, MacAskill, Mark G, Dey, Damini, Baker, Andrew H, Leipsic, Jonathon, Berman, Daniel S, Sellers, Stephanie L, Newby, David E, Dweck, Marc R, and Slomka, Piotr J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease - Coronary Heart Disease, Atherosclerosis, Cardiovascular, Heart Disease, Clinical Research, Aged, Calcinosis, Calcium, Coronary Angiography, Coronary Artery Disease, Disease Progression, Female, Humans, Male, Middle Aged, Plaque, Atherosclerotic, Predictive Value of Tests, Sodium Fluoride, F-18-NaF, CABG, coronary artery bypass graft, coronary artery disease, PET/CT, (18)F-NaF, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

ObjectivesThe aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression.BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.MethodsPatients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery.ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting.ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.

Published
2022

11. Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial

Author

Kuronuma, Keiichiro, van Diemen, Pepijn A., Han, Donghee, Lin, Andrew, Grodecki, Kajetan, Kwiecinski, Jacek, Motwani, Manish, McElhinney, Priscilla, Tomasino, Guadalupe Flores, Park, Caroline, Kwan, Alan, Tzolos, Evangelos, Klein, Eyal, Shou, Benjamin, Tamarappoo, Balaji, Cadet, Sebastien, Danad, Ibrahim, Driessen, Roel S., Berman, Daniel S., Slomka, Piotr J., Dey, Damini, and Knaapen, Paul

Published
2023
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12. Observer repeatability and interscan reproducibility of 18F-sodium fluoride coronary microcalcification activity

Author

Tzolos, Evangelos, Kwiecinski, Jacek, Lassen, Martin Lyngby, Cadet, Sebastien, Adamson, Philip D, Moss, Alastair J, Joshi, Nikhil, Williams, Michelle C, van Beek, Edwin JR, Dey, Damini, Berman, Daniel S, Dweck, Marc R, Newby, David E, and Slomka, Piotr J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Biomedical Imaging, Atherosclerosis, Cardiovascular, Clinical Research, Heart Disease - Coronary Heart Disease, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Calcinosis, Fluorine Radioisotopes, Humans, Observer Variation, Positron Emission Tomography Computed Tomography, Reproducibility of Results, Sodium, Sodium Fluoride, Motion correction, PET, CT, cardiac PET, F-18-NaF, vulnerable plaque, coronary microcalcification activity, 18F-NaF, PET/CT, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundWe aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA).MethodsPatients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level.ResultsIn 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary18F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively.ConclusionsCMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.

Published
2022

13. Machine Learning with 18F-Sodium Fluoride PET and Quantitative Plaque Analysis on CT Angiography for the Future Risk of Myocardial Infarction

Author

Kwiecinski, Jacek, Tzolos, Evangelos, Meah, Mohammed N, Cadet, Sebastien, Adamson, Philip D, Grodecki, Kajetan, Joshi, Nikhil V, Moss, Alastair J, Williams, Michelle C, van Beek, Edwin JR, Berman, Daniel S, Newby, David E, Dey, Damini, Dweck, Marc R, and Slomka, Piotr J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Heart Disease - Coronary Heart Disease, Biomedical Imaging, Atherosclerosis, Cardiovascular, Clinical Research, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Positron Emission Tomography Computed Tomography, myocardial infarction, CT, F-18-NaF PET, quantitative plaque analysis, machine-learning, 18F-NaF PET, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

Coronary 18F-sodium fluoride (18F-NaF) PET and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and 18F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40-59) months of follow-up. On univariable receiver-operator-curve analysis, only 18F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18F-NaF PET), we achieved a substantial improvement (P = 0.008 versus 18F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model.

Published
2022

16. Comparison of diabetes to other prognostic predictors among patients referred for cardiac stress testing: A contemporary analysis from the REFINE SPECT Registry

Author

Han, Donghee, Rozanski, Alan, Gransar, Heidi, Tzolos, Evangelos, Miller, Robert J. H., Sharir, Tali, Einstein, Andrew J., Fish, Mathews B., Ruddy, Terrence D., Kaufmann, Philipp A., Sinusas, Albert J., Miller, Edward J., Bateman, Timothy M., Dorbala, Sharmila, Di Carli, Marcelo, Liang, Joanna X., Hu, Lien-Hsin, Dey, Damini, Berman, Daniel S., and Slomka, Piotr J.

Published
2022
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17. Noninvasive In Vivo Coronary Artery Thrombus Imaging

Author

Tzolos, Evangelos, Bing, Rong, Andrews, Jack, MacAskill, Mark G., Tavares, Adriana A.S., Macnaught, Gillian, Clark, Tim, Mills, Nicholas L., Fujisawa, Takeshi, Nash, Jennifer, Dey, Damini, Slomka, Piotr J., Koglin, Norman, Stephens, Andrew W., Deutsch, Marcus-Andre, van Beek, Edwin J.R., Williams, Michelle C., Hermann, Sven, Hugenberg, Verena, Dweck, Marc R., and Newby, David E.

Published
2023
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18. Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease

Author

Kwiecinski, Jacek, Tzolos, Evangelos, Adamson, Philip D, Cadet, Sebastien, Moss, Alastair J, Joshi, Nikhil, Williams, Michelle C, van Beek, Edwin JR, Dey, Damini, Berman, Daniel S, Newby, David E, Slomka, Piotr J, and Dweck, Marc R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Atherosclerosis, Prevention, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aged, Computed Tomography Angiography, Coronary Artery Disease, Female, Fluorine Radioisotopes, Humans, Male, Middle Aged, Myocardial Infarction, Positron-Emission Tomography, Prognosis, coronary artery disease, coronary computed tomography, coronary event risk prediction, F-18-NaF PET, myocardial infarction, (18)F-NaF PET, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether 18F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent 18F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary 18F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p 1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.ConclusionsIn patients with established coronary artery disease, 18F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.

Published
2020

19. Sex differences in computed tomography angiography-derived coronary plaque burden in relation to invasive fractional flow reserve

Author

Han, Donghee, van Diemen, Pepijn, Kuronuma, Keiichiro, Lin, Andrew, Motwani, Manish, McElhinney, Priscilla, Tomasino, Guadalupe Flores, Park, Caroline, Kwan, Alan, Tzolos, Evangelos, Klein, Eyal, Grodecki, Kajetan, Shou, Benjamin, Tamarappoo, Balaji, Cadet, Sebastien, Danad, Ibrahim, Driessen, Roel S., Berman, Daniel S., Slomka, Piotr J., Dey, Damini, and Knaapen, Paul

Published
2023
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20. Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack—Brief Report

Author

Whittington, Beth, Tzolos, Evangelos, Bing, Rong, Andrews, Jack, Lucatelli, Christophe, MacAskill, Mark G., Tavares, Adriana A.S., Clark, Tim, Mills, Nicholas L., Nash, Jennifer, Dey, Damini, Slomka, Piotr J., Koglin, Norman, Stephens, Andrew W., van Beek, Edwin J.R., Smith, Colin, Dweck, Marc R., Williams, Michelle C., Whiteley, William, Wardlaw, Joanna M., and Newby, David E.

Published
2023
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21. Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning

Author

Singh, Ananya, Miller, Robert J.H., Otaki, Yuka, Kavanagh, Paul, Hauser, Michael T., Tzolos, Evangelos, Kwiecinski, Jacek, Van Kriekinge, Serge, Wei, Chih-Chun, Sharir, Tali, Einstein, Andrew J., Fish, Mathews B., Ruddy, Terrence D., Kaufmann, Philipp A., Sinusas, Albert J., Miller, Edward J., Bateman, Timothy M., Dorbala, Sharmila, Di Carli, Marcelo, Liang, Joanna X., Huang, Cathleen, Han, Donghee, Dey, Damini, Berman, Daniel S., and Slomka, Piotr J.

Published
2023
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22. Quantifying microcalcification activity in the thoracic aorta

Author

Fletcher, Alexander J., Lembo, Maria, Kwiecinski, Jacek, Syed, Maaz B. J., Nash, Jennifer, Tzolos, Evangelos, Bing, Rong, Cadet, Sebastien, MacNaught, Gillian, van Beek, Edwin J. R., Moss, Alistair J., Doris, Mhairi K., Walker, Niki L., Dey, Damini, Adamson, Philip D., Newby, David E., Slomka, Piotr J., and Dweck, Marc R.

Published
2022
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25. Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease

Author

Fletcher, Alexander J., Tew, Yong Y., Tzolos, Evangelos, Joshi, Shruti S., Kaczynski, Jakub, Nash, Jennifer, Debono, Samuel, Lembo, Maria, Kwiecinski, Jacek, Bing, Rong, Syed, Maaz B.J., Doris, Mhairi K., van Beek, Edwin J.R., Moss, Alistair J., Jenkins, William S., Walker, Niki L., Joshi, Nikhil V., Pawade, Tania A., Adamson, Philip D., Whiteley, William N., Wardlaw, Joanna M., Slomka, Piotr J., Williams, Michelle C., Newby, David E., and Dweck, Marc R.

Published
2022
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26. Pericoronary Adipose Tissue Attenuation, Low-Attenuation Plaque Burden, and 5-Year Risk of Myocardial Infarction

Author

Tzolos, Evangelos, Williams, Michelle C., McElhinney, Priscilla, Lin, Andrew, Grodecki, Kajetan, Flores Tomasino, Guadalupe, Cadet, Sebastien, Kwiecinski, Jacek, Doris, Mhairi, Adamson, Philip D., Moss, Alastair J., Alam, Shirjel, Hunter, Amanda, Shah, Anoop S.V., Mills, Nicholas L., Pawade, Tania, Wang, Chengjia, Weir-McCall, Jonathan R., Roditi, Giles, van Beek, Edwin J.R., Shaw, Leslee J., Nicol, Edward D., Berman, Daniel S., Slomka, Piotr J., Dweck, Marc R., Newby, David E., and Dey, Damini

Published
2022
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27. 18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus

Author

Bing, Rong, Deutsch, Marcus-André, Sellers, Stephanie L., Corral, Carlos Alcaide, Andrews, Jack P.M., van Beek, Edwin J.R., Bleiziffer, Sabine, Burchert, Wolfgang, Clark, Tim, Dey, Damini, Friedrichs, Kai, Gummert, Jan F., Koglin, Norman, Leipsic, Jonathon A., Lindner, Oliver, MacAskill, Mark G., Milting, Hendrik, Pessotto, Renzo, Preuss, Rainer, Raftis, Jennifer B., Rudolph, Tanja K., Rudolph, Volker, Slomka, Piotr, Stephens, Andrew W., Tavares, Adriana, Tzolos, Evangelos, Weir, Nick, White, Audrey C., Williams, Michelle C., Zabel, Reinhard, Dweck, Marc R., Hugenberg, Verena, and Newby, David E.

Published
2022
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29. Deep learning-enabled coronary CT angiography for plaque and stenosis quantification and cardiac risk prediction: an international multicentre study

Author

Lin, Andrew, Manral, Nipun, McElhinney, Priscilla, Killekar, Aditya, Matsumoto, Hidenari, Kwiecinski, Jacek, Pieszko, Konrad, Razipour, Aryabod, Grodecki, Kajetan, Park, Caroline, Otaki, Yuka, Doris, Mhairi, Kwan, Alan C, Han, Donghee, Kuronuma, Keiichiro, Flores Tomasino, Guadalupe, Tzolos, Evangelos, Shanbhag, Aakash, Goeller, Markus, Marwan, Mohamed, Gransar, Heidi, Tamarappoo, Balaji K, Cadet, Sebastien, Achenbach, Stephan, Nicholls, Stephen J, Wong, Dennis T, Berman, Daniel S, Dweck, Marc, Newby, David E, Williams, Michelle C, Slomka, Piotr J, and Dey, Damini

Published
2022
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31. Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

Author

Kwiecinski, Jacek, Wang, Kang-Ling, Tzolos, Evangelos, Moss, Alastair, Daghem, Marwa, Adamson, Philip D., Dey, Damini, Molek-Dziadosz, Patrycja, Dawson, Dana, Arumugam, Parthiban, Sabharwal, Nikant, Greenwood, John P., Townend, John N., Calvert, Patrick A., Rudd, James HF., Berman, Daniel, Verjans, Johan W., Williams, Michelle C., Slomka, Piotr, and Dweck, Marc R.

Subjects
SEX factors in disease, POSITRON emission tomography, MYOCARDIAL infarction, CORONARY artery disease, ATHEROSCLEROTIC plaque
Abstract

Introduction: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27–434] versus 205 [51–571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0–6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28–12.28; p < 0.001). Conclusion: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

Author

Geers, Jolien, Rong Bing, Pawade, Tania A., Doris, Mhairi K., Daghem, Marwa, Fletcher, Alexander J., White, Audrey C., Forsyth, Laura, Evans, Emily, Kwieciński, Jacek, Williams, Michelle C., van Beek, Edwin J. R., Soongu Kwak, Peeters, Frederique E. C. M., Tzolos, Evangelos, Slomka, Piotr J., Lucatelli, Christophe, Ralston, Stuart H., Prendergast, Bernard, and Newby, David E.

Published
2024
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33. Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis.

Author

Arsenault, Benoit J., Loganath, Krithika, Girard, Arnaud, Botezatu, Simona, Zheng, Kang H., Tzolos, Evangelos, Abdoun, Kathia, Tastet, Lionel, Capoulade, Romain, Côté, Nancy, Craig, Neil, Chan, Kwan L., Tam, James W., Teo, Koon K., Couture, Christian, Clavel, Marie-Annick, Mathieu, Patrick, Thériault, Sébastien, Stroes, Erik S. G., and Newby, David E.

Published
2024
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34. Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

Author

Kaiser, Yannick, Daghem, Marwa, Tzolos, Evangelos, Meah, Mohammed N., Doris, Mhairi K., Moss, Alistair J., Kwiecinski, Jacek, Kroon, Jeffrey, Nurmohamed, Nick S., van der Harst, Pim, Adamson, Philip D., Williams, Michelle C., Dey, Damini, Newby, David E., Stroes, Erik S.G., Zheng, Kang H., and Dweck, Marc R.

Published
2022
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39. First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Author

IRAS OH Toxicology, IRAS – One Health Toxicology, Andrews, Jack P.M., Joshi, Shruti S., Tzolos, Evangelos, Syed, Maaz B., Cuthbert, Hayley, Crica, Livia E., Lozano, Neus, Okwelogu, Emmanuel, Raftis, Jennifer B., Bruce, Lorraine, Poland, Craig A., Duffin, Rodger, Fokkens, Paul H.B., Boere, A. John F., Leseman, Daan L.A.C., Megson, Ian L., Whitfield, Phil D., Ziegler, Kerstin, Tammireddy, Seshu, Hadjidemetriou, Marilena, Bussy, Cyrill, Cassee, Flemming R., Newby, David E., Kostarelos, Kostas, Miller, Mark R., IRAS OH Toxicology, IRAS – One Health Toxicology, Andrews, Jack P.M., Joshi, Shruti S., Tzolos, Evangelos, Syed, Maaz B., Cuthbert, Hayley, Crica, Livia E., Lozano, Neus, Okwelogu, Emmanuel, Raftis, Jennifer B., Bruce, Lorraine, Poland, Craig A., Duffin, Rodger, Fokkens, Paul H.B., Boere, A. John F., Leseman, Daan L.A.C., Megson, Ian L., Whitfield, Phil D., Ziegler, Kerstin, Tammireddy, Seshu, Hadjidemetriou, Marilena, Bussy, Cyrill, Cassee, Flemming R., Newby, David E., Kostarelos, Kostas, and Miller, Mark R.

Published
2024

40. Machine Learning From Quantitative Coronary Computed Tomography Angiography Predicts Fractional Flow Reserve–Defined Ischemia and Impaired Myocardial Blood Flow

Author

Lin, Andrew, van Diemen, Pepijn A., Motwani, Manish, McElhinney, Priscilla, Otaki, Yuka, Han, Donghee, Kwan, Alan, Tzolos, Evangelos, Klein, Eyal, Kuronuma, Keiichiro, Grodecki, Kajetan, Shou, Benjamin, Rios, Richard, Manral, Nipun, Cadet, Sebastien, Danad, Ibrahim, Driessen, Roel S., Berman, Daniel S., Nørgaard, Bjarne L., Slomka, Piotr J., Knaapen, Paul, and Dey, Damini

Published
2022
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43. EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland

Author

Warren, Alex, primary, McCall, Philip, additional, Proudfoot, Alastair, additional, Gillon, Stuart, additional, Abu-Arafeh, Ahmad, additional, McKnight, Angus John, additional, Mudie, Rosemary, additional, Armstrong, David, additional, Tzolos, Evangelos, additional, Livesey, John Andrew, additional, Sinclair, Andrew, additional, Baston, Veronica, additional, Dalzell, Jonathan, additional, Owen, Deborah, additional, Fleming, Lucy, additional, Scott, Ian, additional, Puxty, Alex, additional, Lee, Matthew MY, additional, Walker, Fiona, additional, Hobson, Simon, additional, Campbell, Euan, additional, Kinsella, Michael, additional, McGinnigle, Eilidh, additional, Docking, Robert, additional, Price, Grant, additional, Ramsay, Alex, additional, Bauld, Richard, additional, Herron, Suzanne, additional, Lone, Nazir I, additional, Mills, Nicholas L, additional, and Hartley, Louise, additional

Published
2023
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44. EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland.

Author

Warren, Alex, McCall, Philip, Proudfoot, Alastair, Gillon, Stuart, Abu-Arafeh, Ahmad, McKnight, Angus John, Mudie, Rosemary, Armstrong, David, Tzolos, Evangelos, Livesey, John Andrew, Sinclair, Andrew, Baston, Veronica, Dalzell, Jonathan, Owen, Deborah, Fleming, Lucy, Scott, Ian, Puxty, Alex, Lee, Matthew MY, Walker, Fiona, and Hobson, Simon

Published
2024
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48. Temporal Changes in Coronary18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis

Author

Daghem, Marwa, primary, Adamson, Philip D., additional, Wang, Kang-Ling, additional, Doris, Mhairi, additional, Bing, Rong, additional, van Beek, Edwin J.R., additional, Forsyth, Laura, additional, Williams, Michelle C., additional, Tzolos, Evangelos, additional, Dey, Damini, additional, Slomka, Piotr J., additional, Dweck, Marc R., additional, Newby, David E., additional, and Moss, Alastair J., additional

Published
2023
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50. Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack

Author

Whittington, Beth, Tzolos, Evangelos, Bing, Rong, Andrews, Jack, Lucatelli, Christophe, MacAskill, Mark G, Tavares, Adriana A S, Clark, Tim, Mills, Nicholas L, Nash, Jennifer, Dey, Damini, Slomka, Piotr J, Koglin, Norman, Stephens, Andrew W, van Beek, Edwin J R, Smith, Colin, Dweck, Marc R, Williams, Michelle C, Whiteley, William, Wardlaw, Joanna M, and Newby, David E

Abstract

BACKGROUND: 18F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke. METHODS: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) was assessed in the carotid arteries and brain. RESULTS: 18F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only, and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 participants had >50% stenosis and 3 had nonstenotic disease. One case had bilateral stenotic disease (>70%), but only the culprit carotid artery demonstrated 18F-GP1 uptake. The average uptake was higher in the culprit (median maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 6.45 [4.89-7.65]), areas of acute infarction on computed tomography correlated with brain 18F-GP1 uptake in 6 cases. Ex vivo autoradiography of postmortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage. CONCLUSIONS: 18F-GP1 positron emission tomography and computed tomography angiography is a novel noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03943966.

Published
2023

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