ISSN: 2394-8418
Journal of Dental Problems and Solutions
Research Article       Open Access      Peer-Reviewed

Do dental screening and treatments prior to heart valve interventions help prevent prosthetic valve endocarditis? A systematic review

Adriana Jacoba Kouwenberg1*, G Mensink1, MWA Van Geldorp2, J Schaap3, RG Bentvelsen4,5 and JE Bergsma1,6

1Department of Maxillofacial Surgery, Amphia Hospital, Molengracht 21, 4841CK, Breda, Netherlands
2Department of Cardiothoracic Surgery, Amphia Hospital, Molengracht 21, 4841CK, Breda, Netherlands
3Department of Cardiology, Amphia Hospital, Molengracht 21, 4841CK, Breda, Netherlands
4Microvida Laboratory for Medical Microbiology, Amphia Hospital, Molengracht 21, 4841CK, Breda, Netherlands
5Department of Medical Microbiology, Leiden University Medical Center, Hippocratespad 19, 2333 ZD, Leiden, Netherlands
6ACTA Dental Department, Gustav Mahlerlaan 3004. 1081 LA, Amsterdam, Netherlands
*Corresponding author: Adriana Jacoba Kouwenberg, Department of Maxillofacial Surgery, Amphia Hospital, Molengracht 21, 4818 CK, Breda, Netherlands, Tel: +31(0)765953111; Fax: +31(0)765953430; E-mail: hkouwenberg@amphia.nl
Received: 26 October, 2022 | Accepted: 13 December, 2022 | Published: 14 December, 2022

Cite this as

Kouwenberg AJ, Mensink G, Geldorp MV, Schaap J, Bentvelsen RG, et al. (2022) Do dental screening and treatments prior to heart valve interventions help prevent prosthetic valve endocarditis? A systematic review. J Dent Probl Solut 9(2): 055-061. DOI: 10.17352/2394-8418.000118

Copyright License

© 2022 Kouwenberg AJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Routine screening for infectious dental foci prior to elective heart valve replacement may help prevent postoperative Prosthetic Valve Endocarditis (PVE), a potentially fatal complication. This systematic review assesses the effect of routine screening for infectious dental foci on the incidence of postoperative PVE. The Cochrane Library, PubMed and EMBASE databases were all searched for relevant primary studies. The GRADE system was used to rate the studies. Three primary studies with a very low level of evidence were included in the review. No significant difference was found between the incidence of PVE in groups with or without routine screening for infectious dental foci prior to heart valve replacement. The results of this review do not support or disprove the need for preoperative screening for infectious dental foci to prevent PVE in patients undergoing heart valve replacement. Further research is necessary.

Introduction

In the Netherlands, most cardiothoracic surgery referral centers prefer screening for infectious dental foci before patients are approved for heart valve replacement. This screening includes a clinical and X-ray examination of dental pathology compliant with the national NVMKA guideline. The screening and subsequent treatments (when necessary) aim to prevent postoperative Prosthetic Valve Endocarditis (PVE) within one year of valve replacement. However, the relevance of such screening is unclear.

The incidence of PVE after heart valve replacement is low (1%-6%) [1,2], but it is a life-threatening complication with a mortality rate of 50%-60% [3]. Typical bacteria related to infective endocarditis include Viridans group streptococci, such as S. bovis, Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corodens, Kingella kingae, K. denitrificans, Staphylococcus aureus and community-acquired enterococci in the absence of a primary focus [4-6]. The majority of these bacteria are commensal in the oral-pharyngeal region.

The mouth is well-known as a possible focus for infections occurring elsewhere in the body [7]. A focus is defined as a source of inflammation and the center of a disease process. Periodontitis and other dental diseases can serve as a primary focus for PVE [8-10]. Predisposing cardiac lesions, previous valve replacement, male sex and a stenotic valve are also associated with infective endocarditis [3-11]. In addition, the removal of dental foci prior to heart valve surgery may be mentally and physically stressful for some patients, and the effects of removing dental foci on the risk of PVE are unclear. Therefore, this review assesses the effects of dental screening and treatments on the incidence of postoperative PVE in patients undergoing heart valve replacement.

Materials and methods

Eligibility criteria

All studies, with the exception of guidelines, letters, position papers, consensus statements, and reviews available by the same author, published between 1980 and April 2022 were included in this review (Table 1). All included studies were in English, German, or Dutch and included adults (>18 years of age). The literature search was performed in May 2022 by an author and a library information specialist at Amphia Hospital and the Leiden University Medical Center. The Cochrane Library, PubMed, and EMBASE databases were searched using appropriate search terms (Figure 1, Table 2).

To provide a clear structure and ensure transparent reporting of the results, the PRISMA guidelines were used to conduct this systematic review [12].

Study selection

Two authors assessed the extracted studies by title and abstract. Then, the full texts of selected studies were assessed (Table 3). When the eligibility of a study was unclear, the study underwent a full-text assessment. There were no disagreements during the screening process.

Quality of evidence

The GRADE method was used to rate the quality of the included primary studies, which were categorized as high, moderate, low, or very low [13,14].

Data parameters

The number of patients, patient age, patient sex, length of follow-up, type of intervention, control group, and relevant outcomes was extracted from the studies. The primary outcome measurement was PVE and the intended independent study variables were dental foci or dental screening. Descriptive statistics were used to summarize the data set.

Meta-analysis

The incidence of PVE was calculated in the intervention and control groups of the three studies included in this review. The data were analyzed using Review Manager Version 5.4.1 (Cochrane, London). An overall risk ratio and risk difference of PVE were calculated using a dichotomous setting with an inverse variance and, due to the expected heterogenicity, a random effect. The heterogenicity was calculated using the I2 and Chi-square coefficients. The confidence intervals were set at 95%.

Results

Search results

Two articles were retrieved from the Cochrane library, 111 from PubMed, and 245 from Embase (Figure 2). After removing duplicates and assessing the titles and abstracts, ten studies underwent a full-text assessment. Two articles were found to be eligible for inclusion in this review. A search of the references of the ten full-text articles resulted in an additional study that was included in this review (Table 4). The GRADE method was used to rate the quality of the included studies (Table 5). Extracted data from the included studies were bundled in Table 6.

A meta-analysis was conducted using data from the three included studies to determine the effects of dental screening on the risk of PVE. The incidence of PVE was not significantly different between patients who underwent preoperative dental screening and those who did not (p = 0.74). There was moderate heterogeneity between the studies (p = 0.16, I2 = 46%) (Figure 3). The risk difference for developing PVE was 0%, indicating no overall effect between the screening and no screening groups (Figure 4).

Discussion

This systematic review assesses the effect of preoperative dental screening on the risk of PVE in patients who underwent a heart valve replacement. However, this review only includes three studies with low-GRADE ratings. No significant differences in the risk of PVE between patients who underwent preoperative dental screening and those who did not were identified. Furthermore, a meta-analysis of these studies was less reliable due to the heterogeneity of the study populations, control groups, and follow-up periods. The results of the dental screenings and subsequent treatments are unclear in the included studies. Therefore, the benefits of preoperative dental screening on PVE risk remain unclear [15,16].

The incidence of PVE in the studies included in this review ranges from 0.3%-8.4%. This wide range may be due to differences in the onset of PVE and the limited follow-up period in two of the included studies. Early PVE is defined as a disease within one year of surgery, and late PVE occurs more than one year after surgery. The differences in early and late PVE may be important, as the valve implant may be contaminated during or directly after the valve surgery or may replicate valve endocarditis in a non-implant natural valve. The types of PVE have different origins (including focal entrance and type of bacteria) and prevention methods [1,5,6]. And are most likely not only caused by dental foci.

Two studies included in this review [17,18] have a short follow-up period (3-6 months), which may account for the lower incidence of PVE, as late PVE is not included or partially included. The incidence of PVE in the remaining study [13] included in this review is high compared to other previous studies [20-22]. This high incidence of PVE should be interpreted with caution as it is not explained in the previous study [19].

One study in this review included a higher rate of PVE in men (11%) than in women (6%) and found that PVE tended to occur in younger patients, though no possible reasons for these results were provided [19]. A higher incidence of PVE in men (4.6% vs. 2.6% in women) was also reported by Myllykangas, et al. [23]. As previously reported, the mortality rate of coronary heart disease is higher in men than in women [24]. It has also been reported that men have a higher incidence of periodontitis and oral cancer and worse oral hygiene than women [25]. These risk factors may contribute to the higher incidence of PVE in men.

To understand the association between dental foci and PVE, the relationship between oral and systemic health must be studied. While several studies have reported associations between dental infections and coronary heart disease diabetes, osteoporosis, respiratory diseases, and poor pregnancy outcomes, the relationship between oral and systemic health remains unclear. Odontogenic bacteremia may lead to systemic infections, though these infections are often mild in healthy patients. However, odontogenic bacteremia may lead to severe infection if not sufficiently treated. Therefore, an understanding of the role of oral health and the risks related to poor oral health is important.

The effects of dental screening on the incidence of early PVE remain unclear [26]. The three studies included in this review concluded that there is a relationship between dental screening and treatment that cannot be supported by the current evidence. The necessity of preoperative dental screening to prevent PVE is unclear. More research is required to understand this relationship.

Patients requiring valve surgery typically have physical and psychological comorbidities. Dental treatments may result in burdens to an already-stressed patient, resulting in worsened conditions, including malnutrition [27-29]. Dental screening prior to heart valve surgery often leads to tooth extractions and 44% of patients are stressed when faced with tooth extractions [30]. The surgical treatment of dental foci may require medication changes or prophylactic antibiotics, which are inconvenient for patients, though not life-threatening [31].

When no dental screening or treatment is conducted prior to heart valve replacement, the overall cost of care is reduced. Furthermore, cardiac surgery will not be delayed by dental treatments. Some dental findings do not require treatment. However, obvious dental pathology must be treated. The European Society of Cardiology (ESC) guidelines strongly recommend strict oral hygiene and follow-up to prevent infectious endocarditis in patients at high risk of PVE, especially after cardiovascular interventions. Furthermore, despite previous research showing that minor oral surgeries can be performed safely in patients receiving antiplatelets or anticoagulants, patients who did not discontinue anticoagulant therapy had significantly increased intraoperative bleeding and a higher incidence of complications after dental treatment [32,33]. Therefore, changes to the patient’s anticoagulant regimen should include drugs with fewer risks prior to dental treatment. The resolution of dental problems prior to valve replacement should be considered to avoid changes to the postoperative anticoagulation regimen [34,35].

Therefore, the necessity and efficacy of dental screening and treatments prior to heart valve replacement remain unclear. However, as only three studies with a low level of evidence were included in this review, more research with a higher level of evidence is needed. A prospective, randomized study with a longer follow-up period (≥ 12 months) or a multicenter cohort study is recommended.

In conclusion, the results of this review do not support or disprove the need for preoperative dental screening for the prevention of PVE after heart valve replacement. More research is necessary to investigate the effects of dental screening on the risk of PVE due to the lack of evidence found in the current literature.

The authors would like to thank Mrs. F. Renkens (information specialist at the library of Amphia Hospital) and Mr. J. Plevier (information specialist at the library of Leiden University Medical Center) for helping with the search strategy.

  1. Groves P. Valve disease: Surgery of valve disease: late results and late complications. Heart. 2001 Dec;86(6):715-21. doi: 10.1136/heart.86.6.715. PMID: 11711480; PMCID: PMC1730041.
  2. Calderwood SB, Swinski LA, Waternaux CM, Karchmer AW, Buckley MJ. Risk factors for the development of prosthetic valve endocarditis. Circulation. 1985 Jul;72(1):31-7. doi: 10.1161/01.cir.72.1.31. PMID: 4006134.
  3. Amat-Santos IJ, Ribeiro HB, Urena M, Allende R, Houde C, Bédard E, Perron J, DeLarochellière R, Paradis JM, Dumont E, Doyle D, Mohammadi S, Côté M, San Roman JA, Rodés-Cabau J. Prosthetic valve endocarditis after transcatheter valve replacement: a systematic review. JACC Cardiovasc Interv. 2015 Feb;8(2):334-346. doi: 10.1016/j.jcin.2014.09.013. PMID: 25700757.
  4. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med. 1994 Mar;96(3):200-9. doi: 10.1016/0002-9343(94)90143-0. PMID: 8154507.
  5. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, Dulgheru R, El Khoury G, Erba PA, Iung B, Miro JM, Mulder BJ, Plonska-Gosciniak E, Price S, Roos-Hesselink J, Snygg-Martin U, Thuny F, Tornos Mas P, Vilacosta I, Zamorano JL; ESC Scientific Document Group. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015 Nov 21;36(44):3075-3128. doi: 10.1093/eurheartj/ehv319. Epub 2015 Aug 29. PMID: 26320109.
  6. Baddour LM, Wilson WR, Bayer AS. Endocarditis, and Kawasaki disease of the Council on Cardiovascular Disease in the young, Council on Clinical Cardiology, council on cardiovascular surgery and anesthesia, and Stroke Council. Infective endocarditis in adults: Diagnosis. Circulation. Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. 2015 October 13; 132(15):1435-86. doi: 10.1161/CIR.0000000000000296. Epub September 15 2015. Erratum in: Circulation. Erratum. 2015 October 27; 132(17):e215 in: Circulation. 134(8):e113. Erratum. 2016 August 23 in: Circulation. e78-e79. 2018 July 31;138(5). PMID: 26373316.
  7. Miller WD. Diseases of the Human Body Which Have Been Traced to the Action of Mouth-Bacteria. Am J Dent Sci. 1891 Nov;25(7):311-319. PMID: 30749695; PMCID: PMC6061594.
  8. Lockhart PB, Brennan MT, Thornhill M, Michalowicz BS, Noll J, Bahrani-Mougeot FK, Sasser HC. Poor oral hygiene as a risk factor for infective endocarditis-related bacteremia. J Am Dent Assoc. 2009 Oct;140(10):1238-44. doi: 10.14219/jada.archive.2009.0046. PMID: 19797553; PMCID: PMC2770162.
  9. Barco CT. Prevention of infective endocarditis: a review of the medical and dental literature. J Periodontol. 1991 Aug;62(8):510-23. doi: 10.1902/jop.1991.62.8.510. PMID: 1920019.
  10. Nord CE, Heimdahl A. Cardiovascular infections: bacterial endocarditis of oral origin. Pathogenesis and prophylaxis. J Clin Periodontol. 1990 Aug;17(7 ( Pt 2)):494-6. doi: 10.1111/j.1365-2710.1992.tb01221.x. PMID: 2202745.
  11. Griffin MR, Wilson WR, Edwards WD, O'Fallon WM, Kurland LT. Infective endocarditis. Olmsted County, Minnesota, 1950 through 1981. JAMA. 1985 Sep 6;254(9):1199-202. doi: 10.1001/jama.254.9.1199. PMID: 4021062.
  12. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009 Jul 21;339:b2700. doi: 10.1136/bmj.b2700. PMID: 19622552; PMCID: PMC2714672.
  13. Brozek JL, Akl EA, Alonso-Coello P, Lang D, Jaeschke R, Williams JW, Phillips B, Lelgemann M, Lethaby A, Bousquet J, Guyatt GH, Schünemann HJ; GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions. Allergy. 2009 May;64(5):669-77. doi: 10.1111/j.1398-9995.2009.01973.x. PMID: 19210357.
  14. Brozek JL, Akl EA, Jaeschke R, Lang DM, Bossuyt P, Glasziou P, Helfand M, Ueffing E, Alonso-Coello P, Meerpohl J, Phillips B, Horvath AR, Bousquet J, Guyatt GH, Schünemann HJ; GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies. Allergy. 2009 Aug;64(8):1109-16. doi: 10.1111/j.1398-9995.2009.02083.x. Epub 2009 May 29. PMID: 19489757.
  15. Cotti E, Arrica M, Di Lenarda A, Serri SB, Bassareo P, Padeletti L, Mercuro G. The perioperative dental screening and management of patients undergoing cardiothoracic, vascular surgery and other cardiovascular invasive procedures: A systematic review. Eur J Prev Cardiol. 2017 Mar;24(4):409-425. doi: 10.1177/2047487316682348. Epub 2017 Jan 17. PMID: 28094561.
  16. Guntheroth WG. How important are dental procedures as a cause of infective endocarditis? Am J Cardiol. 1984 Oct 1;54(7):797-801. doi: 10.1016/s0002-9149(84)80211-8. PMID: 6486031.
  17. Rao NR, Treister N, Axtell A, Muhlbauer J, He P, Lau A, Icyda R, Heng E, Rinewalt D, McGurk S, Kennedy K, Kaneko T, Cameron D, Sroussi H. Preoperative dental screening prior to cardiac valve surgery and 90-day postoperative mortality. J Card Surg. 2020 Nov;35(11):2995-3003. doi: 10.1111/jocs.14957. Epub 2020 Aug 16. PMID: 33111448.
  18. Hakeberg M, Dernevik L, Gatzinsky P, Eklöf C, Kennergren C, Jontell M. The significance of oral health and dental treatment for the postoperative outcome of heart valve surgery. Scand Cardiovasc J. 1999;33(1):5-8. doi: 10.1080/14017439950141966. PMID: 10093852.
  19. de Souza AF, Rocha AL, Castro WH, Ferreira FM, Gelape CL, Travassos DV, da Silva TA. Dental care before cardiac valve surgery: Is it important to prevent infective endocarditis? Int J Cardiol Heart Vasc. 2016 Jul 7;12:57-62. doi: 10.1016/j.ijcha.2016.07.001. PMID: 28616544; PMCID: PMC5454162.
  20. Fauchier L, Bisson A, Herbert J, Lacour T, Bourguignon T, Etienne CS, Bernard A, Deharo P, Bernard L, Babuty D. Incidence and outcomes of infective endocarditis after transcatheter aortic valve implantation versus surgical aortic valve replacement. Clin Microbiol Infect. 2020 Oct;26(10):1368-1374. doi: 10.1016/j.cmi.2020.01.036. Epub 2020 Feb 6. PMID: 32036047.
  21. Kolte D, Goldsweig A, Kennedy KF, Abbott JD, Gordon PC, Sellke FW, Ehsan A, Sodha N, Sharaf BL, Aronow HD. Comparison of Incidence, Predictors, and Outcomes of Early Infective Endocarditis after Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in the United States. Am J Cardiol. 2018 Dec 15;122(12):2112-2119. doi: 10.1016/j.amjcard.2018.08.054. Epub 2018 Sep 13. PMID: 30292332.
  22. Ando T, Ashraf S, Villablanca PA, Telila TA, Takagi H, Grines CL, Afonso L, Briasoulis A. Meta-Analysis Comparing the Incidence of Infective Endocarditis Following Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement. Am J Cardiol. 2019 Mar 1;123(5):827-832. doi: 10.1016/j.amjcard.2018.11.031. Epub 2018 Dec 3. PMID: 30545481.
  23. Myllykangas ME, Aittokallio J, Gunn J, Sipilä J, Rautava P, Kytö V. Sex Differences in Long-Term Outcomes After Surgical Aortic Valve Replacement: A Nationwide Propensity-matched Study. J Cardiothorac Vasc Anesth. 2020 Apr;34(4):932-939. doi: 10.1053/j.jvca.2019.10.011. Epub 2019 Oct 11. PMID: 31732381.
  24. Bots SH, Peters SAE, Woodward M. Sex differences in coronary heart disease and stroke mortality: a global assessment of the effect of ageing between 1980 and 2010. BMJ Glob Health. 2017 Mar 27;2(2):e000298. doi: 10.1136/bmjgh-2017-000298. PMID: 28589033; PMCID: PMC5435266.
  25. Lipsky MS, Su S, Crespo CJ, Hung M. Men and Oral Health: A Review of Sex and Gender Differences. Am J Mens Health. 2021 May-Jun;15(3):15579883211016361. doi: 10.1177/15579883211016361. PMID: 33993787; PMCID: PMC8127762.
  26. Patil R, Gondivkar SM, Gadbail AR, Yuwanati M, Mankar M (Gadbail), Likhitkar M, Sarode S, Sarode G, Patil S. Role of oral foci in systemic diseases: An update; January 2017. International Journal of Contemporary Dental and Medical Reviews; DOI:10.15713/ins.ijcdmr.115.
  27. Chermesh I, Hajos J, Mashiach T, Bozhko M, Shani L, Nir RR, Bolotin G. Malnutrition in cardiac surgery: food for thought. Eur J Prev Cardiol. 2014 Apr;21(4):475-83. doi: 10.1177/2047487312452969. Epub 2012 Jun 27. PMID: 22739686.
  28. Stoppe C, Goetzenich A, Whitman G, Ohkuma R, Brown T, Hatzakorzian R, Kristof A, Meybohm P, Mechanick J, Evans A, Yeh D, McDonald B, Chourdakis M, Jones P, Barton R, Tripathi R, Elke G, Liakopoulos O, Agarwala R, Lomivorotov V, Nesterova E, Marx G, Benstoem C, Lemieux M, Heyland DK. Role of nutrition support in adult cardiac surgery: a consensus statement from an International Multidisciplinary Expert Group on Nutrition in Cardiac Surgery. Crit Care. 2017 Jun 5;21(1):131. doi: 10.1186/s13054-017-1690-5. PMID: 28583157; PMCID: PMC5460477.
  29. Stoppe C, Goetzenich A, Whitman G, Ohkuma R, Brown T, Hatzakorzian R, Kristof A, Meybohm P, Mechanick J, Evans A, Yeh D, McDonald B, Chourdakis M, Jones P, Barton R, Tripathi R, Elke G, Liakopoulos O, Agarwala R, Lomivorotov V, Nesterova E, Marx G, Benstoem C, Lemieux M, Heyland DK. Role of nutrition support in adult cardiac surgery: a consensus statement from an International Multidisciplinary Expert Group on Nutrition in Cardiac Surgery. Crit Care. 2017 Jun 5;21(1):131. doi: 10.1186/s13054-017-1690-5. PMID: 28583157; PMCID: PMC5460477.
  30. Scott BJ, Leung KC, McMillan AS, Davis DM, Fiske J. A transcultural perspective on the emotional effect of tooth loss in complete denture wearers. Int J Prosthodont. 2001 Sep-Oct;14(5):461-5. PMID: 12066643.
  31. Lockhart PB, Loven B, Brennan MT, Fox PC. The evidence base for the efficacy of antibiotic prophylaxis in dental practice. J Am Dent Assoc. 2007 Apr;138(4):458-74; quiz 534-5, 437. doi: 10.14219/jada.archive.2007.0198. PMID: 17403736.
  32. Calcia TBB, Oballe HJR, de Oliveira Silva AM, Friedrich SA, Muniz FWMG. Is alteration in single drug anticoagulant/antiplatelet regimen necessary in patients who need minor oral surgery? A systematic review with meta-analysis. Clin Oral Investig. 2021 Jun;25(6):3369-3381. doi: 10.1007/s00784-021-03882-z. Epub 2021 Mar 23. PMID: 33758999.
  33. Ockerman A, Bornstein MM, Leung YY, Li SKY, Politis C, Jacobs R. Incidence of bleeding after minor oral surgery in patients on dual antiplatelet therapy: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2020 Jan;49(1):90-98. doi: 10.1016/j.ijom.2019.06.002. Epub 2019 Jun 24. PMID: 31248706.
  34. Baumann Kreuziger L, Karkouti K, Tweddell J, Massicotte MP. Antithrombotic therapy management of adult and pediatric cardiac surgery patients. J Thromb Haemost. 2018 Nov;16(11):2133-2146. doi: 10.1111/jth.14276. Epub 2018 Sep 30. PMID: 30153372.
  35. Sousa-Uva M, Head SJ, Milojevic M, Collet JP, Landoni G, Castella M, Dunning J, Gudbjartsson T, Linker NJ, Sandoval E, Thielmann M, Jeppsson A, Landmesser U. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg. 2018 Jan 1;53(1):5-33. doi: 10.1093/ejcts/ezx314. PMID: 29029110.