Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2019

Open Access 01-12-2019 | CT Angiography | Research article

Progression of coronary atherosclerotic plaque burden and relationship with adverse cardiovascular event in asymptomatic diabetic patients

Authors: Junjie Yang, Guanhua Dou, Christian Tesche, Carlo N. De Cecco, Brian E. Jacobs, U. Joseph Schoepf, Yundai Chen

Published in: BMC Cardiovascular Disorders | Issue 1/2019

Login to get access

Abstract

Background

The heterogeneity of risk in patients with diabetes mellitus (DM) is acknowledged in new guidelines promulgating different treatment recommendations for diabetics at low cardiac risk. We performed a retrospective longitudinal follow-up study to evaluate coronary plaque progression and its impact on cardiac events in asymptomatic diabetic patients.

Methods

Data of 197 asymptomatic patients (63.1 ± 17 years, 60% males) with DM and suspected coronary artery disease (CAD) who underwent clinically indicated dual-source cardiac computed tomography (CT) were retrospectively analyzed. Patients with DM received standard of care treatment. Patients were classified into two groups based on CT coronary artery calcium scores (CACS): A, CACS> 10; B, CACS≤10. Progression of coronary plaque burden in both groups was evaluated and compared by baseline and follow-up coronary CT angiography (CCTA) using semi-automated plaque analysis and quantification software. Follow-up data were retrospectively gathered from medical records and endpoints of cardiac events were recorded via prospective phone-calls. The impacts of plaque composition and progression on cardiac events were specifically assessed.

Results

Patients with CACS> 10 showed an increase in dense coronary calcium volume, while patients with CACS≤10 had a more pronounced increase in the volume of low-attenuation “lipid-rich” plaque components between CCTA acquisitions. The composite endpoint occurred in 20 patients (10.2%) after a median follow-up period of 41.8 months. Furthermore, at follow-up CCTA, the presence of CACS> 10 (adjusted odds ratio, 0.701; 95% CI, 0.612–0.836), increase of dense calcium volume (OR, 0.860 95% CI, 0.771–0.960), and lipid volume (OR, 1.013; 95% CI, 1.007–1.020) were all independent predictors of cardiac events.

Conclusion

Asymptomatic patients with DM experienced plaque progression as well as progression to “overt or silent CAD”. The relative increase in plaque volume was associated with subsequent cardiac events, and the coronary calcification seemed to be inversely related to the outcome in asymptomatic diabetic patients.
Literature
1.
go back to reference Emerging Risk Factors C, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22.CrossRef Emerging Risk Factors C, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22.CrossRef
2.
go back to reference Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and Other Societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701.CrossRef Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and Other Societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701.CrossRef
3.
go back to reference Farkou ME. ACP journal Club. Review: Diabetes is not a coronary disease equivalent. Ann Intern Med. 2009;151(4):JC2-6–7. Farkou ME. ACP journal Club. Review: Diabetes is not a coronary disease equivalent. Ann Intern Med. 2009;151(4):JC2-6–7.
4.
go back to reference Zellweger MJ, Hachamovitch R, Kang X, Hayes SW, Friedman JD, Germano G, Pfisterer ME, Berman DS. Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients. Eur Heart J. 2004;25(7):543–50.CrossRef Zellweger MJ, Hachamovitch R, Kang X, Hayes SW, Friedman JD, Germano G, Pfisterer ME, Berman DS. Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients. Eur Heart J. 2004;25(7):543–50.CrossRef
5.
go back to reference American Diabetes A. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36(Suppl 1):S11–66.CrossRef American Diabetes A. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36(Suppl 1):S11–66.CrossRef
6.
go back to reference Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547–55.CrossRef Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547–55.CrossRef
7.
go back to reference Kwan AC, May HT, Cater G, Sibley CT, Rosen BD, Lima JA, Rodriguez K, Lappe DL, Muhlestein JB, Anderson JL, et al. Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study. Radiology. 2014;272(3):690–9.CrossRef Kwan AC, May HT, Cater G, Sibley CT, Rosen BD, Lima JA, Rodriguez K, Lappe DL, Muhlestein JB, Anderson JL, et al. Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study. Radiology. 2014;272(3):690–9.CrossRef
8.
go back to reference Zellweger MJ, Maraun M, Osterhues HH, Keller U, Muller-Brand J, Jeger R, Pfister O, Burkard T, Eckstein F, von Felten S, et al. Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy. J Am Coll Cardiol Img. 2014;7(10):1001–10.CrossRef Zellweger MJ, Maraun M, Osterhues HH, Keller U, Muller-Brand J, Jeger R, Pfister O, Burkard T, Eckstein F, von Felten S, et al. Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy. J Am Coll Cardiol Img. 2014;7(10):1001–10.CrossRef
9.
go back to reference van den Hoogen IJ, de Graaf MA, Roos CJ, Leen AC, Kharagjitsingh AV, Wolterbeek R, Kroft LJ, Wouter Jukema J, Bax JJ, Scholte AJ. Prognostic value of coronary computed tomography angiography in diabetic patients without chest pain syndrome. J Nucl Cardiol. 2016;23(1):24–36.CrossRef van den Hoogen IJ, de Graaf MA, Roos CJ, Leen AC, Kharagjitsingh AV, Wolterbeek R, Kroft LJ, Wouter Jukema J, Bax JJ, Scholte AJ. Prognostic value of coronary computed tomography angiography in diabetic patients without chest pain syndrome. J Nucl Cardiol. 2016;23(1):24–36.CrossRef
10.
go back to reference Kramer CK, Zinman B, Gross JL, Canani LH, Rodrigues TC, Azevedo MJ, Retnakaran R. Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis. BMJ. 2013;346:f1654.CrossRef Kramer CK, Zinman B, Gross JL, Canani LH, Rodrigues TC, Azevedo MJ, Retnakaran R. Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis. BMJ. 2013;346:f1654.CrossRef
11.
go back to reference Bauer RW, Thilo C, Chiaramida SA, Vogl TJ, Costello P, Schoepf UJ. Noncalcified atherosclerotic plaque burden at coronary CT angiography: a better predictor of ischemia at stress myocardial perfusion imaging than calcium score and stenosis severity. AJR Am J Roentgenol. 2009;193(2):410–8.CrossRef Bauer RW, Thilo C, Chiaramida SA, Vogl TJ, Costello P, Schoepf UJ. Noncalcified atherosclerotic plaque burden at coronary CT angiography: a better predictor of ischemia at stress myocardial perfusion imaging than calcium score and stenosis severity. AJR Am J Roentgenol. 2009;193(2):410–8.CrossRef
12.
go back to reference Tesche C, De Cecco CN, Caruso D, Baumann S, Renker M, Mangold S, Dyer KT, Varga-Szemes A, Baquet M, Jochheim D, et al. Coronary CT angiography derived morphological and functional quantitative plaque markers correlated with invasive fractional flow reserve for detecting hemodynamically significant stenosis. J Cardiovasc Comput Tomogr. 2016;10(3):199–206.CrossRef Tesche C, De Cecco CN, Caruso D, Baumann S, Renker M, Mangold S, Dyer KT, Varga-Szemes A, Baquet M, Jochheim D, et al. Coronary CT angiography derived morphological and functional quantitative plaque markers correlated with invasive fractional flow reserve for detecting hemodynamically significant stenosis. J Cardiovasc Comput Tomogr. 2016;10(3):199–206.CrossRef
13.
go back to reference Tesche C, Plank F, De Cecco CN, Duguay TM, Albrecht MH, Varga-Szemes A, Bayer RRN, Yang J, Jacks IL, Gramer BM, et al. Prognostic implications of coronary CT angiography-derived quantitative markers for the prediction of major adverse cardiac events. J Cardiovasc Comput Tomogr. 2016;10(6):458–65.CrossRef Tesche C, Plank F, De Cecco CN, Duguay TM, Albrecht MH, Varga-Szemes A, Bayer RRN, Yang J, Jacks IL, Gramer BM, et al. Prognostic implications of coronary CT angiography-derived quantitative markers for the prediction of major adverse cardiac events. J Cardiovasc Comput Tomogr. 2016;10(6):458–65.CrossRef
14.
go back to reference Ito H, Motoyama S, Sarai M, Kawai H, Harigaya H, Kan S, Kato S, Anno H, Takahashi H, Naruse H, et al. Characteristics of plaque progression detected by serial coronary computed tomography angiography. Heart Vessel. 2014;29(6):743–9.CrossRef Ito H, Motoyama S, Sarai M, Kawai H, Harigaya H, Kan S, Kato S, Anno H, Takahashi H, Naruse H, et al. Characteristics of plaque progression detected by serial coronary computed tomography angiography. Heart Vessel. 2014;29(6):743–9.CrossRef
15.
go back to reference Oberoi S, Meinel FG, Schoepf UJ, Nance JW, De Cecco CN, Gebregziabher M, Costello P, Weininger M. Reproducibility of noncalcified coronary artery plaque burden quantification from coronary CT angiography across different image analysis platforms. AJR Am J Roentgenol. 2014;202(1):W43–9.CrossRef Oberoi S, Meinel FG, Schoepf UJ, Nance JW, De Cecco CN, Gebregziabher M, Costello P, Weininger M. Reproducibility of noncalcified coronary artery plaque burden quantification from coronary CT angiography across different image analysis platforms. AJR Am J Roentgenol. 2014;202(1):W43–9.CrossRef
16.
go back to reference Blackmon KN, Streck J, Thilo C, Bastarrika G, Costello P, Schoepf UJ. Reproducibility of automated noncalcified coronary artery plaque burden assessment at coronary CT angiography. J Thorac Imaging. 2009;24(2):96–102.CrossRef Blackmon KN, Streck J, Thilo C, Bastarrika G, Costello P, Schoepf UJ. Reproducibility of automated noncalcified coronary artery plaque burden assessment at coronary CT angiography. J Thorac Imaging. 2009;24(2):96–102.CrossRef
17.
go back to reference Nadjiri J, Hausleiter J, Jahnichen C, Will A, Hendrich E, Martinoff S, Hadamitzky M. Incremental prognostic value of quantitative plaque assessment in coronary CT angiography during 5 years of follow up. J Cardiovasc Comput Tomogr. 2016;10(2):97–104.CrossRef Nadjiri J, Hausleiter J, Jahnichen C, Will A, Hendrich E, Martinoff S, Hadamitzky M. Incremental prognostic value of quantitative plaque assessment in coronary CT angiography during 5 years of follow up. J Cardiovasc Comput Tomogr. 2016;10(2):97–104.CrossRef
18.
go back to reference Gu H, Gao Y, Wang H, Hou Z, Han L, Wang X, Lu B. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367–72.CrossRef Gu H, Gao Y, Wang H, Hou Z, Han L, Wang X, Lu B. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367–72.CrossRef
19.
go back to reference Elkeles RS, Godsland IF, Feher MD, Rubens MB, Roughton M, Nugara F, Humphries SE, Richmond W, Flather MD, Group PS. Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study. Eur Heart J. 2008;29(18):2244–51.CrossRef Elkeles RS, Godsland IF, Feher MD, Rubens MB, Roughton M, Nugara F, Humphries SE, Richmond W, Flather MD, Group PS. Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study. Eur Heart J. 2008;29(18):2244–51.CrossRef
20.
go back to reference Cury RC, Abbara S, Achenbach S, Agatston A, Berman DS, Budoff MJ, Dill KE, Jacobs JE, Maroules CD, Rubin GD, et al. Coronary artery disease - reporting and data system (CAD-RADS): an expert consensus document of SCCT, ACR and NASCI: endorsed by the ACC. J Am Coll Cardiol Img. 2016;9(9):1099–113.CrossRef Cury RC, Abbara S, Achenbach S, Agatston A, Berman DS, Budoff MJ, Dill KE, Jacobs JE, Maroules CD, Rubin GD, et al. Coronary artery disease - reporting and data system (CAD-RADS): an expert consensus document of SCCT, ACR and NASCI: endorsed by the ACC. J Am Coll Cardiol Img. 2016;9(9):1099–113.CrossRef
21.
go back to reference Benedek T, Gyongyosi M, Benedek I. Multislice computed tomographic coronary angiography for quantitative assessment of culprit lesions in acute coronary syndromes. Can J Cardiol. 2013;29(3):364–71.CrossRef Benedek T, Gyongyosi M, Benedek I. Multislice computed tomographic coronary angiography for quantitative assessment of culprit lesions in acute coronary syndromes. Can J Cardiol. 2013;29(3):364–71.CrossRef
22.
go back to reference Agarwal S, Cox AJ, Herrington DM, Jorgensen NW, Xu J, Freedman BI, Carr JJ, Bowden DW. Coronary calcium score predicts cardiovascular mortality in diabetes: diabetes heart study. Diabetes Care. 2013;36(4):972–7.CrossRef Agarwal S, Cox AJ, Herrington DM, Jorgensen NW, Xu J, Freedman BI, Carr JJ, Bowden DW. Coronary calcium score predicts cardiovascular mortality in diabetes: diabetes heart study. Diabetes Care. 2013;36(4):972–7.CrossRef
23.
go back to reference Kim U, Leipsic JA, Sellers SL, Shao M, Blanke P, Hadamitzky M, Kim YJ, Conte E, Andreini D, Pontone G, et al. Natural history of diabetic coronary atherosclerosis by quantitative measurement of serial coronary computed tomographic angiography: results of the PARADIGM study (progression of atherosclerotic plaque determined by computed tomographic angiography imaging). J Am Coll Cardiol Img. 2018;11(10):1461–71.CrossRef Kim U, Leipsic JA, Sellers SL, Shao M, Blanke P, Hadamitzky M, Kim YJ, Conte E, Andreini D, Pontone G, et al. Natural history of diabetic coronary atherosclerosis by quantitative measurement of serial coronary computed tomographic angiography: results of the PARADIGM study (progression of atherosclerotic plaque determined by computed tomographic angiography imaging). J Am Coll Cardiol Img. 2018;11(10):1461–71.CrossRef
24.
go back to reference Banach M, Serban C, Sahebkar A, Mikhailidis DP, Ursoniu S, Ray KK, Rysz J, Toth PP, Muntner P, Mosteoru S, et al. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med. 2015;13:229.CrossRef Banach M, Serban C, Sahebkar A, Mikhailidis DP, Ursoniu S, Ray KK, Rysz J, Toth PP, Muntner P, Mosteoru S, et al. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med. 2015;13:229.CrossRef
25.
go back to reference McCullough PA, Fazel P, Choi JW. Screening, diagnosis, and management of CAD in asymptomatic diabetic patients. J Am Coll Cardiol Img. 2014;7(10):1011–2.CrossRef McCullough PA, Fazel P, Choi JW. Screening, diagnosis, and management of CAD in asymptomatic diabetic patients. J Am Coll Cardiol Img. 2014;7(10):1011–2.CrossRef
26.
go back to reference Hadamitzky M, Taubert S, Deseive S, Byrne RA, Martinoff S, Schomig A, Hausleiter J. Prognostic value of coronary computed tomography angiography during 5 years of follow-up in patients with suspected coronary artery disease. Eur Heart J. 2013;34(42):3277–85.CrossRef Hadamitzky M, Taubert S, Deseive S, Byrne RA, Martinoff S, Schomig A, Hausleiter J. Prognostic value of coronary computed tomography angiography during 5 years of follow-up in patients with suspected coronary artery disease. Eur Heart J. 2013;34(42):3277–85.CrossRef
27.
go back to reference Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, Rubin GD, American College of Cardiology Foundation Appropriate Use Criteria Task F, Society of Cardiovascular Computed T, American College of R, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation appropriate use criteria task force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the north American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation. 2010;122(21):e525–55.PubMed Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, Rubin GD, American College of Cardiology Foundation Appropriate Use Criteria Task F, Society of Cardiovascular Computed T, American College of R, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation appropriate use criteria task force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the north American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation. 2010;122(21):e525–55.PubMed
28.
go back to reference Kumamaru KK, Kondo T, Kumamaru H, Amanuma M, George E, Rybicki FJ. Repeat coronary computed tomographic angiography in patients with a prior scan excluding significant stenosis. Circ Cardiovasc Imaging. 2014;7(5):788–95.CrossRef Kumamaru KK, Kondo T, Kumamaru H, Amanuma M, George E, Rybicki FJ. Repeat coronary computed tomographic angiography in patients with a prior scan excluding significant stenosis. Circ Cardiovasc Imaging. 2014;7(5):788–95.CrossRef
29.
go back to reference Tesche C, De Cecco CN, Vliegenthart R, Duguay TM, Stubenrauch AC, Rosenberg RD, Varga-Szemes A, Bayer RR 2nd, Yang J, Ebersberger U, et al. Coronary CT angiography-derived quantitative markers for predicting in-stent restenosis. J Cardiovasc Comput Tomogr. 2016;10(5):377–83.CrossRef Tesche C, De Cecco CN, Vliegenthart R, Duguay TM, Stubenrauch AC, Rosenberg RD, Varga-Szemes A, Bayer RR 2nd, Yang J, Ebersberger U, et al. Coronary CT angiography-derived quantitative markers for predicting in-stent restenosis. J Cardiovasc Comput Tomogr. 2016;10(5):377–83.CrossRef
30.
go back to reference Henzler T, Porubsky S, Kayed H, Harder N, Krissak UR, Meyer M, Sueselbeck T, Marx A, Michaely H, Schoepf UJ, et al. Attenuation-based characterization of coronary atherosclerotic plaque: comparison of dual source and dual energy CT with single-source CT and histopathology. Eur J Radiol. 2011;80(1):54–9.CrossRef Henzler T, Porubsky S, Kayed H, Harder N, Krissak UR, Meyer M, Sueselbeck T, Marx A, Michaely H, Schoepf UJ, et al. Attenuation-based characterization of coronary atherosclerotic plaque: comparison of dual source and dual energy CT with single-source CT and histopathology. Eur J Radiol. 2011;80(1):54–9.CrossRef
31.
go back to reference Marfella R, Sardu C, Balestrieri ML, Siniscalchi M, Minicucci F, Signoriello G, Calabro P, Mauro C, Pieretti G, Coppola A, et al. Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis. Diabetol Metab Syndr. 2018;10:1.CrossRef Marfella R, Sardu C, Balestrieri ML, Siniscalchi M, Minicucci F, Signoriello G, Calabro P, Mauro C, Pieretti G, Coppola A, et al. Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis. Diabetol Metab Syndr. 2018;10:1.CrossRef
32.
go back to reference Balestrieri ML, Rizzo MR, Barbieri M, Paolisso P, D'Onofrio N, Giovane A, Siniscalchi M, Minicucci F, Sardu C, D'Andrea D, et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes. 2015;64(4):1395–406.CrossRef Balestrieri ML, Rizzo MR, Barbieri M, Paolisso P, D'Onofrio N, Giovane A, Siniscalchi M, Minicucci F, Sardu C, D'Andrea D, et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes. 2015;64(4):1395–406.CrossRef
Metadata
Title
Progression of coronary atherosclerotic plaque burden and relationship with adverse cardiovascular event in asymptomatic diabetic patients
Authors
Junjie Yang
Guanhua Dou
Christian Tesche
Carlo N. De Cecco
Brian E. Jacobs
U. Joseph Schoepf
Yundai Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2019
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-019-1016-4

Other articles of this Issue 1/2019

BMC Cardiovascular Disorders 1/2019 Go to the issue