Predictors of 18F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography

Jacek Kwiecinski; Damini Dey; Sebastien Cadet; Sang Eun Lee; Balaji Tamarappoo; Yuka Otaki; Phi T. Huynh; John D. Friedman; Mark R. Dweck; David E. Newby; Mijin Yun; Hyuk Jae Chang; Piotr J. Slomka; Daniel S. Berman

doi:10.1093/ehjci/jez152

Predictors of ¹⁸F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography

Jacek Kwiecinski, Damini Dey, Sebastien Cadet, Sang Eun Lee, Balaji Tamarappoo, Yuka Otaki, Phi T. Huynh, John D. Friedman, Mark R. Dweck, David E. Newby, Mijin Yun, Hyuk Jae Chang, Piotr J. Slomka, Daniel S. Berman

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

Abstract

Aims: In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary ¹⁸F-sodium fluoride uptake (¹⁸F-NaF) by positron emission tomography (PET). Methods and results: Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm³ were recruited for ¹⁸F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum ¹⁸F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary ¹⁸F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting ¹⁸F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3-1.8) vs. 1.1 (1.0-1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30-0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm³, 95% CI 0.13-0.27; P < 0.001). Conclusion: In stable CAD patients with HRP, LAP is predictive of ¹⁸F-NaF coronary uptake, but ¹⁸F-NaF is often seen in the absence of LAP. If ¹⁸F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.

Original language	English
Pages (from-to)	58-66
Number of pages	9
Journal	European heart journal cardiovascular Imaging
Volume	21
Issue number	1
DOIs	https://doi.org/10.1093/ehjci/jez152
Publication status	Published - 2020 Jan 1

Bibliographical note

Funding Information:
This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. AdelsonMedical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars Sinai Medical Center.

Funding Information:
This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars–Sinai Medical Center.

Publisher Copyright:
© 2019 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019.

All Science Journal Classification (ASJC) codes

Radiology Nuclear Medicine and imaging
Cardiology and Cardiovascular Medicine

Access to Document

10.1093/ehjci/jez152

Cite this

Kwiecinski, J., Dey, D., Cadet, S., Lee, S. E., Tamarappoo, B., Otaki, Y., Huynh, P. T., Friedman, J. D., Dweck, M. R., Newby, D. E., Yun, M., Chang, H. J., Slomka, P. J., & Berman, D. S. (2020). Predictors of ¹⁸F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography. European heart journal cardiovascular Imaging, 21(1), 58-66. https://doi.org/10.1093/ehjci/jez152

@article{baa796428733442c9becd5464ed6a1bd,

title = "Predictors of 18F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography",

abstract = "Aims: In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results: Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3-1.8) vs. 1.1 (1.0-1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30-0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm3, 95% CI 0.13-0.27; P < 0.001). Conclusion: In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.",

author = "Jacek Kwiecinski and Damini Dey and Sebastien Cadet and Lee, {Sang Eun} and Balaji Tamarappoo and Yuka Otaki and Huynh, {Phi T.} and Friedman, {John D.} and Dweck, {Mark R.} and Newby, {David E.} and Mijin Yun and Chang, {Hyuk Jae} and Slomka, {Piotr J.} and Berman, {Daniel S.}",

note = "Funding Information: This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. AdelsonMedical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars Sinai Medical Center. Funding Information: This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars–Sinai Medical Center. Publisher Copyright: {\textcopyright} 2019 Published on behalf of the European Society of Cardiology. All rights reserved. {\textcopyright} The Author(s) 2019.",

year = "2020",

month = jan,

day = "1",

doi = "10.1093/ehjci/jez152",

language = "English",

volume = "21",

pages = "58--66",

journal = "European heart journal cardiovascular Imaging",

issn = "2047-2404",

publisher = "Oxford University Press",

number = "1",

}

Kwiecinski, J, Dey, D, Cadet, S, Lee, SE, Tamarappoo, B, Otaki, Y, Huynh, PT, Friedman, JD, Dweck, MR, Newby, DE, Yun, M, Chang, HJ, Slomka, PJ & Berman, DS 2020, 'Predictors of ¹⁸F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography', European heart journal cardiovascular Imaging, vol. 21, no. 1, pp. 58-66. https://doi.org/10.1093/ehjci/jez152

TY - JOUR

T1 - Predictors of 18F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography

AU - Kwiecinski, Jacek

AU - Dey, Damini

AU - Cadet, Sebastien

AU - Lee, Sang Eun

AU - Tamarappoo, Balaji

AU - Otaki, Yuka

AU - Huynh, Phi T.

AU - Friedman, John D.

AU - Dweck, Mark R.

AU - Newby, David E.

AU - Yun, Mijin

AU - Chang, Hyuk Jae

AU - Slomka, Piotr J.

AU - Berman, Daniel S.

N1 - Funding Information: This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. AdelsonMedical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars Sinai Medical Center. Funding Information: This work was supported in part by grants R01HL135557 and R01HL133616 from the National Heart, Lung, and Blood Institute/ National Institute of Health (NHLBI/NIH) and by a grant from the Dr. Miriam & Sheldon G. Adelson Medical Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.E.N. (CH/09/ 002, RE/13/3/30183) and M.R.D. (FS/14/78/31020) are supported by the British Heart Foundation. D.E.N. is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and M.R.D. of Sir Jules Thorn Award for Biomedical Research Award (2015). D.S.B., D.D., and P.J.S. receive software royalties from Cedars–Sinai Medical Center. Publisher Copyright: © 2019 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Aims: In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results: Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3-1.8) vs. 1.1 (1.0-1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30-0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm3, 95% CI 0.13-0.27; P < 0.001). Conclusion: In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.

AB - Aims: In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results: Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3-1.8) vs. 1.1 (1.0-1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30-0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm3, 95% CI 0.13-0.27; P < 0.001). Conclusion: In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.

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