Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network
Abstract
1. Introduction
2. Patients and Methods
2.1. Study Design
2.2. Data Collection, Statistical Analysis and Illustrations
3. Results
3.1. Endocarditis Network
3.2. Patient Population
3.3. Morbidities and Outcomes
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Delgado, V.; Ajmone Marsan, N.; De Waha, S.; Bonaros, N.; Brida, M.; Burri, H.; Caselli, S.; Doenst, T.; Ederhy, S.; Erba, P.A.; et al. 2023 ESC Guidelines for the management of endocarditis. Eur. Heart J. 2023, 44, 3948–4042. [Google Scholar] [CrossRef]
- Diab, M.; Franz, M.; Hagel, S.; Guenther, A.; Struve, A.; Musleh, R.; Penzel, A.; Sponholz, C.; Lehmann, T.; Kuehn, H.; et al. Impact of an in-hospital endocarditis team and a state-wide endocarditis network on perioperative outcomes. J. Clin. Med. 2021, 10, 4734. [Google Scholar] [CrossRef]
- Davierwala, P.M.; Marin-Cuartas, M.; Misfeld, M.; Borger, M.A. The value of an “Endocarditis Team”. Ann. Cardiothorac. Surg. 2019, 8, 621–629. [Google Scholar] [CrossRef]
- Patel, S.K.; Hassan, S.M.A.; Côté, M.; Leis, B.; Yanagawa, B. Current trends and challenges in infective endocarditis. Curr. Opin. Cardiol. 2025, 40, 75–84. [Google Scholar] [CrossRef] [PubMed]
- Saha, S.; Dudakova, A.; Danner, B.C.; Kutschka, I.; Schulze, M.H.; Niehaus, H. Bacterial Spectrum and Infective Foci in Patients Operated for Infective Endocarditis: Time to Rethink Strategies? Thorac. Cardiovasc. Surg. 2022, 71, 2–11. [Google Scholar] [CrossRef]
- Bayer, A.S.; Bolger, A.F.; Taubert, K.A.; Wilson, W.; Steckelberg, J.; Karchmer, A.W.; Levison, M.; Chambers, H.F.; Dajani, A.S.; Gewitz, M.H.; et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998, 98, 2936–2948. [Google Scholar] [CrossRef] [PubMed]
- Baddour, L.M.; Wilson, W.R.; Bayer, A.S.; Fowler, V.G.; Tleyjeh, I.M.; Rybak, M.J.; Barsic, B.; Lockhart, P.B.; Gewitz, M.H.; Levison, M.E.; et al. Infective endocarditis in adults: Diagnosis, antimicrobial therapy, and management of complications: A scientific statement for healthcare professionals from the American Heart Association. Circulation 2015, 132, 1435–1486. [Google Scholar] [CrossRef]
- Cahill, T.J.; Baddour, L.M.; Habib, G.; Hoen, B.; Salaun, E.; Pettersson, G.B.; Schafers, H.J.; Prendergast, B.D. Challenges in Infective Endocarditis. J. Am. Coll. Cardiol. 2017, 69, 325–344. [Google Scholar] [CrossRef] [PubMed]
- Habib, G.; Lancellotti, P.; Antunes, M.J.; Bongiorni, M.G.; Casalta, J.P.; Del Zotti, F.; Dulgheru, R.; El Khoury, G.; Erba, P.A.; Iung, B.; et al. 2015 ESC Guidelines for the management of infective endocarditis. Eur. Heart J. 2015, 36, 3075–3123. [Google Scholar] [CrossRef]
- German Hospital Directory. Available online: https://www.german-hospital-directory.com/app/search (accessed on 1 June 2025).
- Nashef, S.A.M.; Roques, F.; Sharples, L.D.; Nilsson, J.; Smith, C.; Goldstone, A.R.; Lockowandt, U. Euroscore II. Eur. J. Cardio-Thorac. Surg. 2012, 41, 734–745. [Google Scholar] [CrossRef]
- Di Mauro, M.; Dato, G.M.A.; Barili, F.; Gelsomino, S.; Santè, P.; Corte, A.D.; Carrozza, A.; Della Ratta, E.; Cugola, D.; Galletti, L.; et al. A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE. Int. J. Cardiol. 2017, 241, 97–102. [Google Scholar] [CrossRef]
- Levy, B.; Bastien, O.; Karim, B.; Cariou, A.; Chouihed, T.; Combes, A.; Mebazaa, A.; Megarbane, B.; Plaisance, P.; Ouattara, A.; et al. Experts’ recommendations for the management of adult patients with cardiogenic shock. Ann. Intensive Care 2015, 5, 17. [Google Scholar] [CrossRef]
- Papageorgiou, G.; Grant, S.W.; Takkenberg, J.J.M.; Mokhles, M.M. Statistical primer: How to deal with missing data in scientific research? Interact. Cardiovasc. Thorac. Surg. 2018, 27, 153–158. [Google Scholar] [CrossRef]
- Hickey, G.L.; Kontopantelis, E.; Takkenberg, J.J.M.; Beyersdorf, F. Statistical primer: Checking model assumptions with regression diagnostics. Interact. Cardiovasc. Thorac. Surg. 2019, 28, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Naderi, H.R.; Sheybani, F.; Erfani, S.S. Errors in diagnosis of infective endocarditis. Epidemiol. Infect. 2018, 146, 394–400. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Kim, J.B.; Sastry, B.K.S.; Chen, M. Infective endocarditis. Lancet 2024, 404, 377–392. [Google Scholar] [CrossRef]
- Cabell, C.H.; Abrutyn, E. Progress toward a global understanding of infective endocarditis. Early lessons from the International Collaboration on Endocarditis investigation. Infect. Dis. Clin. N. Am. 2002, 16, 255–272, vii. [Google Scholar] [CrossRef] [PubMed]
- N’Guyen, Y.; Duval, X.; Revest, M.; Saada, M.; Erpelding, M.L.; Selton-Suty, C.; Bouchiat, C.; Delahaye, F.; Chirouze, C.; Alla, F.; et al. Time interval between infective endocarditis first symptoms and diagnosis: Relationship to infective endocarditis characteristics, microorganisms and prognosis. Ann. Med. 2017, 49, 117–125. [Google Scholar] [CrossRef]
- Verhagen, D.W.M.; Hermanides, J.; Korevaar, J.C.; Bossuyt, P.M.M.; Van Den Brink, R.B.A.; Speelman, P.; Van Der Meer, J.T.M. Health-related quality of life and posttraumatic stress disorder among survivors of left-sided native valve endocarditis. Clin. Infect. Dis. 2009, 48, 1559–1565. [Google Scholar] [CrossRef]
- Luehr, M.; Weber, C.; Misfeld, M.; Lichtenberg, A.; Tugtekin, S.-M.; Diab, M.; Saha, S.; Li, Y.; Matsche, K.; Doenst, T.; et al. Virulence of Staphylococcus Infection in Surgically Treated Patients with Endocarditis: A Multicenter Analysis. Ann. Surg. 2022, 277, e1364–e1372. [Google Scholar] [CrossRef]
- Moody, W.; Loudon, M.; Watkin, R.; Steeds, R.; Prendergast, B. Infective endocarditis: Diagnosis delayed during swine flu pandemic. Postgrad. Med. J. 2011, 87, 240. [Google Scholar] [CrossRef]
- Bleibtreu, A.; Arias, P.; Vallois, D.; Debit, A.; Lermuzeaux, M.; Rioux, C.; Cabras, O.; Lucet, J.C.; Choquet, C.; Timsit, J.F.; et al. Delayed management of Staphyloccocus aureus infective endocarditis in a Middle East respiratory syndrome coronavirus possible case hospitalized in 2015 in Paris, France. Clin. Microbiol. Infect. 2017, 23, 416–417. [Google Scholar] [CrossRef]
- ATOE-IMAGBE, O.M.; Azzu, A. A late diagnosis of infective endocarditis (IE) in the COVID-19 Infection: A near fatal experience. Clin. Med. 2024, 24, 100056. [Google Scholar] [CrossRef]
- Rubinovitch, B.; Pittet, D. Infective endocarditis: Too ill to be operated? Crit. Care 2002, 6, 6–8. [Google Scholar] [CrossRef] [PubMed]
- Papadimitriou-Olivgeris, M.; Monney, P.; Frank, M.; Tzimas, G.; Fourre, N.; Zimmermann, V.; Tozzi, P.; Kirsch, M.; Van Hemelrijck, M.; Epprecht, J.; et al. Comparison of the 2015 and 2023 Duke—European Society of Cardiology Criteria Among Patients with Suspected Infective Endocarditis. Clin. Infect. Dis. 2023, 80, 777–783. [Google Scholar] [CrossRef] [PubMed]
- Borger, M.A.; de Waha, S.; Marsan, N.A.; Zühlke, L.; Mestres, C.A.; Fosbol, E.; Bonaros, N.; Pizzi, M.N.; Brida, M.; Sionis, A.; et al. Key priorities for the implementation of the 2023 ESC Guidelines for the management of endocarditis in low-resource settings. Eur. Heart J. Qual. Care Clin. Outcomes 2025, 11, 691–697. [Google Scholar] [CrossRef] [PubMed]
- Saha, S.; Peterss, S.; Mueller, C.; Deseive, S.; Sadoni, S.; Hausleiter, J.; Massberg, S.; Hagl, C.; Joskowiak, D. Cardiac surgery following transcatheter aortic valve replacement. Eur. J. Cardio-Thorac. Surg. 2021, 60, 1149–1155. [Google Scholar] [CrossRef]
- Dhawan, V.K. Infective endocarditis in elderly patients. Clin. Infect. Dis. 2002, 34, 806–812. [Google Scholar] [CrossRef]
- Ursi, M.P.; Durante Mangoni, E.; Rajani, R.; Hancock, J.; Chambers, J.B.; Prendergast, B. Infective Endocarditis in the Elderly: Diagnostic and Treatment Options. Drugs Aging 2019, 36, 115–124. [Google Scholar] [CrossRef]
- Caldonazo, T.; Hagel, S.; Doenst, T.; Kirov, H.; Sá, M.P.; Jacquemyn, X.; Tasoudis, P.; Franz, M.; Diab, M. Conservative Versus Surgical Therapy in Patients with Infective Endocarditis and Surgical Indication—Meta-Analysis of Reconstructed Time-to-Event Data. J. Am. Heart Assoc. 2024, 13, e033404. [Google Scholar] [CrossRef]
- Kang, D.-H.; Kim, Y.-J.; Kim, S.-H.; Sun, B.J.; Kim, D.-H.; Yun, S.-C.; Song, J.-M.; Choo, S.J.; Chung, C.-H.; Song, J.-K.; et al. Early surgery versus conventional treatment for infective endocarditis. N. Engl. J. Med. 2012, 366, 2466–2473. [Google Scholar] [CrossRef] [PubMed]




| Time to Diagnosis <7 Days (n = 509) | Time to Diagnosis >7 Days (n = 198) | p-Value | |
|---|---|---|---|
| Age (years) | 66 (53–74) | 68 (61–76) | <0.001 |
| Male | 365 (71.7) | 142 (71.7) | 1.000 |
| BMI (kg/m2) | 25.0 (22.9–27.7) | 25.2 (23.7–28.0) | 0.386 |
| NYHA Class | 0.019 | ||
| Class I | 25 (4.9) | 5 (2.5) | |
| Class II | 154 (30.4) | 42 (21.2) | |
| Class III | 285 (56.2) | 124 (62.6) | |
| Class IV | 45 (8.9) | 27 (13.6) | |
| EuroSCORE II | 4.6 (2.3–10.0) | 7.4 (3.6–16.8) | 0.001 |
| EndoSCORE | 11.4 (6.9–18.1) | 12.3 (6.9–24.2) | 0.019 |
| Comorbidities | |||
| Arterial Hypertension | 370 (72.7) | 154 (77.8) | 0.181 |
| Insulin-Dependent Diabetes Mellitus | 50 (9.8) | 28 (14.1) | 0.109 |
| Hyperlipoproteinemia | 203 (39.9) | 108 (54.5) | <0.001 |
| Coronary Artery Disease | 0.013 | ||
| Single-Vessel Disease | 46 (9.0) | 32 (16.2) | |
| Two-Vessel Disease | 39 (7.7) | 17 (8.6) | |
| Three-Vessel Disease | 5 (10.8) | 28 (14.1) | |
| Peripheral Artery Disease | 43 (8.4) | 23 (11.6) | 0.197 |
| Atrial Fibrillation | 151 (30.1) | 76 (38.4) | 0.039 |
| Pacemaker | 61 (12.0) | 28 (14.1) | 0.450 |
| PCI/PTCA | 41 (8.1) | 41 (20.7) | <0.001 |
| New Myocardial Infarction | 19 (3.7) | 19 (9.6) | 0.004 |
| Chronic Kidney Disease | 101 (19.8) | 52 (26.3) | 0.068 |
| Dialysis | 23 (4.5) | 8 (4.0) | 1.000 |
| Immunosuppressive Therapy | 41 (8.1) | 21 (10.6) | 0.301 |
| Malignancy | 124 (24.4) | 50 (25.3) | 0.846 |
| Alcohol Abuse (%) | 46 (9.0) | 22 (11.1) | 0.397 |
| PWiD | 27 (5.3) | 4 (2.0) | 0.037 |
| HIV Infection | 3 (0.6) | 3 (1.5) | 0.357 |
| Smoker (%) | 85 (16.7) | 28 (14.1) | 0.426 |
| COPD (%) | 38 (7.5) | 35 (17.7) | <0.001 |
| Previous Cardiac Surgery (%) | 145 (28.5) | 61 (30.8) | 0.580 |
| Clinical Presentation | |||
| Previous Endocarditis (%) | 27 (5.3) | 6 (3.0) | 0.237 |
| Fever (%) | 289 (56.8) | 105 (53.0) | 0.399 |
| Septic Cerebral Embolism (%) | 147 (28.9) | 44 (22.2) | 0.044 |
| ICU Admission (%) | 151 (29.7) | 69 (34.8) | 0.205 |
| Ventilation on Admission (%) | 33 (6.5) | 26 (13.1) | 0.006 |
| Cardiogenic Shock (%) | 90 (17.7) | 48 (24.2) | 0.032 |
| Time to Diagnosis <7 Days (n = 509) | Time to Diagnosis >7 Days (n = 198) | p-Value | |
|---|---|---|---|
| Time to diagnosis (days) | 1 (1–3) | 12 (8–18) | <0.001 |
| Surgical treatment | 366 (71.9) | 102 (51.5) | <0.001 |
| Valves affected | |||
| Prosthetic valve endocarditis | 143 (28.1) | 52 (26.3) | 0.641 |
| TAVR endocarditis | 29 (5.9) | 9 (4.5) | 0.710 |
| Mitral valve | 227 (44.6) | 92 (46.5) | 0.674 |
| Aortic valve | 318 (62.5) | 119 (60.1) | 0.605 |
| Tricuspid valve | 32 (6.3) | 6 (3.0) | 0.096 |
| Pulmonary valve | 1 (0.2) | 1 (0.5) | 0.482 |
| Double-valve endocarditis | 70 (13.8) | 20 (10.1) | 0.210 |
| Triple-valve endocarditis | 2 (0.4) | 0 (0.0) | 1.000 |
| Modified Duke criteria | |||
| Major criteria | |||
| Positive blood cultures | 332 (65.2) | 112 (56.6) | 0.037 |
| Echocardiographic evidence | 461 (90.6) | 174 (87.9) | 0.332 |
| Minor criteria | |||
| Predisposing heart condition or intravenous drug use | 243 (47.7) | 83 (41.9) | 0.179 |
| Fever | 289 (56.8) | 105 (53.0) | 0.399 |
| Vascular phenomena | 197 (38.7) | 54 (27.3) | 0.005 |
| Immunologic phenomena | 20 (3.9) | 4 (2.0) | 0.253 |
| Positive blood culture not meeting major criterion (%) | 77 (15.1) | 54 (27.3) | <0.001 |
| Patients not meeting Duke criteria (%) | 169 (33.2) | 84 (42.4) | 0.023 |
| Pathogens | |||
| BCNIE (%) | 80 (15.7) | 29 (14.6) | 0.817 |
| Gram-positive pathogens (%) | 406 (79.8) | 156 (78.8) | 0.757 |
| Staphylococci | 169 (33.2) | 89 (44.9) | 0.004 |
| CoNS (%) | 45 (8.8) | 22 (11.1) | 0.391 |
| S. aureus (%) | 126 (24.8) | 68 (34.3) | 0.011 |
| Streptococci (%) | 153 (30.1) | 34 (17.2) | <0.001 |
| Enterococci (%) | 66 (13.0) | 28 (14.1) | 0.712 |
| Gram-negative pathogens (%) | 24 (4.7) | 13 (6.6) | 0.348 |
| HACEK pathogens (%) | 9 (1.8) | 1 (0.5) | 0.298 |
| Time to Diagnosis <7 Days (n = 509) | Time to Diagnosis >7 Days (n = 198) | p-Value | |
|---|---|---|---|
| Diagnostics | |||
| Transoesophageal Echocardiography | 475 (93.3) | 190 (96.0) | 0.217 |
| Chest CT | 336 (66.0) | 126 (63.6) | 0.598 |
| Cerebral CT | 317 (62.3) | 122 (61.6) | 0.931 |
| Abdominal CT | 168 (33.0) | 74 (37.4) | 0.290 |
| PET CT | 48 (9.4) | 26 (13.1) | 0.171 |
| Cardiac MRI | 6 (1.2) | 1 (0.5) | 0.680 |
| Cerebral MRI | 111 (21.8) | 44 (22.2) | 0.920 |
| Echocardiography | |||
| LVEF | 0.057 | ||
| >50% | 410 (80.6) | 144 (72.7) | |
| 30–50% | 85 (16.7) | 44 (22.2) | |
| <30% | 14 (2.8) | 10 (5.1) | |
| Pulmonary Hypertension | 86 (16.9) | 56 (28.3) | 0.001 |
| Vegetation | 450 (88.4) | 176 (88.9) | 0.896 |
| Size of Vegetation | 0.005 | ||
| <5 mm | 41 (8.1) | 20 (10.1) | |
| 5–10 mm | 168 (33.0) | 89 (44.9) | |
| >10 mm | 241 (47.3) | 66 (33.3) | |
| Abscess | 111 (21.8) | 36 (18.2) | 0.304 |
| Paravalvular Leakage | 57 (11.2) | 15 (7.6) | 0.168 |
| Time to Diagnosis <7 Days (n = 509) | Time to Diagnosis >7 Days (n = 198) | p-Value | |
|---|---|---|---|
| Morbidities | |||
| Renal replacement therapy | 56 (13.7) | 25 (18.8) | 0.163 |
| ECLS support | 26 (6.4) | 8 (6.0) | 1.000 |
| IABP support | 7 (1.7) | 4 (3.0) | 0.478 |
| Septic shock | 67 (16.5) | 30 (22.4) | 0.122 |
| Pacemaker implantation | 37 (9.1) | 11 (8.2) | 0.862 |
| Tracheostomy | 15 (3.7) | 20 (14.9) | <0.001 |
| Outcomes | |||
| Hospital stay (days) | 22 (14–35) | 25 (15–39) | <0.001 |
| Ventilation time | 16 (8–48) | 24 (8–128) | 0.109 |
| ICU stay | 4 (2–8) | 6 (3–13) | 0.004 |
| In-hospital mortality | 68 (13.4) | 40 (20.2) | 0.027 |
| Discharge | |||
| Cardiac rehabilitation centre | 168 (33.0) | 49 (24.7) | 0.037 |
| Hospital | 161 (31.6) | 65 (32.8) | 0.788 |
| Home | 112 (22.0) | 44 (22.2) | 1.000 |
| OR (95%CI) | p-Value | |
|---|---|---|
| Delayed diagnosis | 1.72 (1.02–2.89) | 0.040 |
| Stroke | 2.07 (1.27–3.40) | 0.004 |
| Age > 75 years | 1.72 (1.01–2.92) | 0.044 |
| Atrial fibrillation | 2.30 (1.40–3.77) | <0.001 |
| LVEF < 30 | 1.48 (0.45–4.92) | 0.519 |
| CAD | 1.01 (0.61–1.68) | 0.972 |
| Tracheostomy | 0.443 (0.145–1.35) | 0.152 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Share and Cite
Saha, S.; Zauner, B.; Kaiser, R.; Rizas, K.; Orban, M.; Massberg, S.; Peterss, S.; Hagl, C.; Joskowiak, D. Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network. J. Clin. Med. 2026, 15, 924. https://doi.org/10.3390/jcm15030924
Saha S, Zauner B, Kaiser R, Rizas K, Orban M, Massberg S, Peterss S, Hagl C, Joskowiak D. Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network. Journal of Clinical Medicine. 2026; 15(3):924. https://doi.org/10.3390/jcm15030924
Chicago/Turabian StyleSaha, Shekhar, Benjamin Zauner, Rainer Kaiser, Konstantinos Rizas, Martin Orban, Steffen Massberg, Sven Peterss, Christian Hagl, and Dominik Joskowiak. 2026. "Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network" Journal of Clinical Medicine 15, no. 3: 924. https://doi.org/10.3390/jcm15030924
APA StyleSaha, S., Zauner, B., Kaiser, R., Rizas, K., Orban, M., Massberg, S., Peterss, S., Hagl, C., & Joskowiak, D. (2026). Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network. Journal of Clinical Medicine, 15(3), 924. https://doi.org/10.3390/jcm15030924

