A 6-year analysis of cardiovascular implantable electronic device-related endocarditis

Authors

Abstract

AimAdvances in interventional cardiology have increased the frequency of use of devices such as cardiovascular implanted electronic devices (CIED) used in cardiac arrhythmias. Endocarditis due to these devices increases morbidity and mortality.
MethodsDemographic data, laboratory tests, results of blood cultures, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) data of 48 patients who developed infective endocarditis due to CIED in our hospital between January 1, 2013 and March 1, 2019 were retrospectively analyzed.
ResultsA total of 48 patients were included in this study. The ratio of females (n=24) and males (n=24) was equal. The mean age of all patients was 55 years. In the surviving patients, in order of frequency of occurrence, hypertension (HT) was in 13 patients (86%), chronic renal failure (CKD) in 9 patients (47%), and diabetes mellitus (DM) in 8 patients (72%). Of the patients who died, 10 (52%) had CRF, 3 (27%) had DM, 2 (66%) had HT and chronic obstructive pulmonary disease (COPD). The most common symptoms in surviving patients were, respectively, fever in 26 (78%), malaise in 19 (76%), respiratory distress in 11 (61%). The most common symptoms in deceased patients were respiratory distress in 7 (%38), fever in 7 (21%), fatigue in 6 (%24); 14 (29%) of the patients referred to our clinic started antibiotic treatment at an external center. Growth was detected in 26 (54%) of all blood cultures. The most frequently isolated pathogens were, respectively, Staphylococcus aureus (n = 11) 42%, Streptococcus spp.(n = 6) 23%, Enterococcus faecium (n = 4) 15%, Citrobacter spp. (n = 2) 7%, Diphtheroid spp.(n=1) 3%, Acinetobacter baumannii (n = 1) 3%, Brucella mitis (n = 1) 3%. Vegetation was observed on the lead in 13 (27%) performed TTEs and/or TEEs. From the time of diagnosis, the average time of surgery was 6 days in surviving patients and 11 days in patients who died.
ConclusionThe number of studies and cases related to endocarditis due to CIEDs is limited in our country. Although CIED-related endocarditis is a rare complication of cardiac device implantation, its morbidity and mortality remain high.

Keywords

Introduction

CIEDs are used in the treatment of symptomatic bradycardia and heart failure in patients at risk of sudden cardiac death due to ventricular arrhythmia.
The total number of CIEDs implanted per 1,000,000 people per year is 247. With the aging of the population, it is predicted that these devices will be implanted more frequently in our country, as in the whole world.¹ In our country, a total of n = 22,732 CIEDs were implanted in 2016, 9993 of which were permanent pacemakers, 3485 cardiac resynchronization therapy devices, and 9254 ICDs (available at: https://www.escardio.org/static_file/Escardio/Subspecialty/EHRA/Publications/Documents/2017/ehra-white-book-2017.pdf).
The Duke criteria are used in the diagnosis of infective endocarditis (IE) due to CIED. Vegetations are seen on device wires, adjacent endocardial surfaces, or on the valve, but the presence of vegetation only at the tip of the wire can be considered as IE.
It is difficult to diagnose cardiac device-related IE. If a patient with a cardiac device has an unexplained fever, infective endocarditis should be considered first.² CIED-associated infective endocarditis accounts for 10% to 23% of all CIED-related infections. Among all infective endocarditis cases, the rate of those associated with CIED is 10% both in our country and worldwide. Although it is recommended to continue IV antibiotic treatment for at least 2 weeks after device removal, if blood culture positivity continues in the first 24 hours after device removal, this period should be extended to 4 weeks.^3,4,5

Materials and Methods

We retrospectively analyzed 48 patients who were followed up in our hospital with the diagnosis of CIED-related endocarditis between January 1, 2013 and March 1, 2019. Patient demographics, TTE/TEE, laboratory findings, causative pathogens and surgical approaches were examined. Ethical approval numbered 2020-3/03-296 and dated 20.04.2020 was obtained from the Non-Interventional Clinical Research Ethics Committee of the Health Sciences University Kartal Kosuyolu Yuksek Ihtisas Training and Research Hospital.
Ethical ApprovalEthics Committee approval for the study was obtained.
Statistics AnalysisDescriptive statistics (mean, median, standard deviation, etc.) were used while summarizing continuous numerical variables. Two-group comparison of numerical variables was analyzed with the Mann-Whitney U test. The statistical significance limit was taken as p<0.05.

Results

The ratio of female and male patients was equal, and the mean age was 55 ± 14.6 years. Mortality developed in n = 3 (17%) female patients and n = 9 (38%) male patients. The mean age of patients living with CIED was 53 ± 11.4 years, and the mean age of patients who died was 64 ± 12.2 years. The median length of hospital stay was 31.5 (29.0 to 33.0) days in patients who survived, and 29.5 (28.0 to 33.5) days in patients who died. The most common symptoms in surviving patients were fever in n = 26 (78%), fatigue in n = 19 (76%), and respiratory distress in n = 11 (61%). Among those who died, respiratory distress was present in n = 7 (38%), fever in n = 7 (21%), and fatigue in n = 6 (24%) (Table 1).
HT, COPD, and obesity were found to be statistically significant (p=0.208, p=0.150, p=0.150). When comorbid factors were taken into account, the underlying disease was significantly higher in those who died (p=0.012). In surviving patients, hypertension (HT) was present in n = 13 (86%), chronic renal failure (CKD) in n = 9 (47%), and diabetes mellitus (DM) in n = 8 (72%). Of the patients who died, n = 10 (52%) had CRF, n = 3 (27%) had DM, and n = 2 (66%) had HT and COPD (Table 2).
Of the n = 48 patients followed up with CIED infection, n = 14 (29.1%) were referred from external centers. In these patients, antibiotics were started before blood cultures were taken. Growth was detected in the blood cultures of n = 26 (54%) patients.
The isolated pathogens, in order of frequency, were Staphylococcus aureus (n = 11, 42%), Streptococcus spp. (n = 6, 23%), Enterococcus faecium (n = 4, 11%), Citrobacter spp. (n = 2, 7%), Diphtheroid spp. (n = 1, 3%), Acinetobacter baumannii (n = 1, 3%), and Brucella mitis (n = 1, 3%).
Of the patients followed up with CIED, n = 33 (68%) had natural valves and n = 15 (31%) had prosthetic valves. Considering valve involvement of vegetation, n = 9 (18%) patients had aortic valve involvement, n = 8 (16%) had mitral valves, and n = 1 (2%) had a tricuspid valve. In TEE and/or TTE performed on the patients, vegetation on the lead was detected in n = 13 (27%) patients. Serum leukocytosis was present in n = 16 (70%) of the surviving patients and n = 7 (30%) of the deceased patients (p=0.311). C-reactive protein (CRP) was higher than 20 mg/dl in n = 27 (80%) of the survivors and in n = 7 (20%) of the deceased patients (p=0.019). There were n = 9 (19%) patients with procalcitonin > 1 ng/ml, and n = 5 (55%) of these patients died.
For various reasons, 25 of 48 patients (52%) received antibiotics before blood cultures were taken. The start of antibiotic therapy in the preliminary diagnosis of CIED infection was 41 hours in living patients and 9.9 hours in deceased patients. One of the problems in treatment was lead removal, which was performed by two different methods. CIEDs in n = 19 patients (39%) were removed percutaneously using instruments such as transvenous manual traction, locking stylet, rotational mechanical dilator sheath systems, and traps. The surgical method was applied in n = 29 (60%) patients.
SurgeryThe mediastinum was reached by median sternotomy under general anesthesia. The patient was heparinized and, after bicaval cannulation of the aorta, cardiopulmonary bypass (CPB) was initiated. The aorta was cross-clamped and cardiac arrest was achieved with warm blood cardioplegia. Then, the inner surface of the right atrium was reached by right atriotomy, the infected and thrombosed lead was examined and removed from the atrium and ventricular wall with sharp and blunt dissections. If there was an additional cardiac problem, an intervention was performed. A temporary intracardiac pacemaker was implanted in all patients when exiting CPB. From the time of diagnosis, the average time of surgery was 6 days in surviving patients and 11 days in patients who died.

Discussion

In a study conducted by Osmonov et al. in our country, in a retrospective study of CIED-related IEs that developed within 31 years in a single center, n = 23 (0.38%) of 5287 patients with CIED were reported to develop IE.⁶ When Aksoy et al. examined the main differences in the characteristics and management of IE between sexes in their 11-year follow-up study of patients with endocarditis, response to antibiotic therapy, need for surgical treatment, surgical intervention rate, and overall in-hospital mortality were similar in both genders.^7,8,9 In our study, the ratio of female and male patients was equal. However, among surviving patients, women were more common (n = 21, 87.5%), and among those who died, men were more common (n = 9, 37.5%).
In the study by Bloom et al., the risk factors most commonly associated with endocarditis were diabetes mellitus and chronic kidney disease.^10,11 In our study, HT was detected in n = 13 (86%) patients, chronic renal failure in n = 9 (47%), and DM in n = 8 (72%), in order of frequency in surviving patients. Of the patients who died, n = 10 (52%) had CRF, n = 3 (27%) had DM, and n = 2 (66%) had HT and COPD.
In the study by Massoure et al., 51% to 80% of n = 155 patients had fever, and 68% to 92% had bacteremia.¹² In a multicenter study by Sohail et al., in n = 177 patients, fever and chills were found in 55.3%, vegetation in 67.6%, and positive blood cultures in 34.5%.¹³ In our study, the most common symptoms in surviving patients were fever in n = 26 (78%), fatigue in n = 19 (76%), and respiratory distress in n = 11 (61%). Among those who died, respiratory distress was present in n = 7 (38%), fever in n = 7 (21%), and fatigue in n = 6 (24%).
In the study conducted by Sohail et al., blood cultures were positive in 77%, vegetation in 67.6%, and positive blood cultures consistent with endocarditis in 34.5% of patients with cardiac device-related infection.¹³ Consistent with other studies, blood culture positivity was found to be 54% in our study. In these patients with preliminary diagnosis of fever of unknown origin, antibiotics were started before blood cultures were taken.
In the study by Rundstrom et al., CRP elevation was observed in 73% to 100% of patients with pacemaker endocarditis and in 34% to 81.8% of leukocytosis cases.¹⁴ In our study, n = 16 (70%) of the surviving patients and n = 7 (30%) of the deceased patients had serum leukocytosis. C-reactive protein (CRP) was higher than 20 mg/dl in n = 27 (80%) of the survivors and n = 7 (20%) of the deceased patients. Staphylococci, especially coagulase-negative Staphylococci, account for 60% to 80% of cases. Polymicrobial infection, Corynebacterium spp., Propionibacterium acnes, Gram-negative bacilli, and Candida spp. are rarely identified as pathogens in CIED infection.¹⁵ In our study, the most frequently isolated pathogens were Staphylococcus aureus (n = 11, 42%), Streptococcus spp. (n = 6, 23%), Enterococcus faecium (n = 4, 11%), Citrobacter spp. (n = 2, 7.6%), Diphtheroid spp. (n = 1, 3.8%), Acinetobacter baumannii (n = 1, 3%), and Brucella mitis (n = 1, 3%).
The role of echocardiography is very important in diagnosing cardiac device-related IE. Echocardiography helps detect electrode vegetation and tricuspid valve involvement and quantify tricuspid regurgitation.¹⁴ In the multicenter study by Athan et al., fever, vegetation, and positive blood culture were high (> 80%). In this study, the sensitivity of TTE was low, vegetations were visualized in 30.4% of patients.¹⁶ In our study, consistent with other studies, vegetation on the lead was observed on ECHO and/or TTE in n = 13 (27%) patients.
In most patients with cardiac device-associated IE, device removal is required with prolonged administration of antibiotics.¹⁴ In many cases, the lead can be removed percutaneously without surgical intervention. However, if the cardiac device was placed several years ago, percutaneous electrode removal becomes difficult. In such cases, surgical intervention is recommended in severe tricuspid valve endocarditis and in patients with large vegetations.¹⁷ In our study, n = 29 (60%) patients underwent surgical treatment.
The 30-day mortality rate for CIED infection is 5% to 8%. Female gender is a high-risk factor for endocarditis. Successfully treated patients have the same prognosis as those who have never been infected.¹⁸ In our study, n = 21 women survived (87%), n = 3 died (17%), and n = 15 (62%) male patients survived, n = 9 died (38%).

Conclusion

In our country, studies and the number of cases of endocarditis related to CIEDs are limited. Although endocarditis from CIEDs is a rare complication of cardiac device implantation, its morbidity and mortality remain high.

Declarations

References

1. Sohail RM, Wilson W, Baddour LM. Infections of nonvalvular cardiovascular devices. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Elsevier Saunders; 2015:1041-1056. doi:10.1016/b978-1-4557-4801-3.00084-9
   Article PubMed Google Scholar
2. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis: new version 2009. Eur Heart J. 2009;30(19):2369-2413. doi:10.1093/eurheartj/ehp285
   Article PubMed Google Scholar
3. Tarakji KG, Ellis CR, Defaye P, Kennergren C. Cardiac implantable electronic device infection in patients at risk. Arrhythm Electrophysiol Rev. 2016;5(1):65-71. doi:10.15420/aer.2015.27.2
   Article PubMed Google Scholar
4. Durante-Mangoni E, Casillo R, Bernardo M. High-dose daptomycin for cardiac implantable electronic device-related infective endocarditis. Clin Infect Dis. 2012;54(3):347-354. doi:10.1093/cid/cir805
   Article PubMed Google Scholar
5. Tascini C, Bongiorni MG, Di Cori A, et al. Cardiovascular implantable electronic device endocarditis treated with daptomycin with or without transvenous removal. Heart Lung. 2012;41(6):e24-e30. doi:10.1016/j.hrtlng.2012.02.002
   Article PubMed Google Scholar
6. Osmonov D, Ozcan KS, Erdinler I, et al. Cardiac device-related endocarditis: 31 years’ experience. J Cardiol. 2013;61(2):175-180. doi:10.1016/j.jjcc.2012.08.019
   Article PubMed Google Scholar
7. Aksoy O, Meyer LT, Cabell CH, Kourany WM, Pappas PA, Sexton DJ. Gender differences in infective endocarditis: pre- and comorbid conditions lead to different management and outcomes in female patients. Scand J Infect Dis. 2007;39(2):101-107. doi:10.1080/00365540600993285
   Article PubMed Google Scholar
8. Aksoy O, Sexton DJ, Wang A, et al. Early surgery in patients with infective endocarditis: a propensity score analysis. Clin Infect Dis. 2007;44(3):364-372. doi:10.1086/510583
   Article PubMed Google Scholar
9. Castillo JC, Anguita MP, Delgado M, et al. Clinical characteristics and prognosis of infective endocarditis in women. Rev Esp Cardiol. 2008;61(1):36-40. doi:10.1016/s1885-5857(08)60066-3
   Article PubMed Google Scholar
10. Bloom H, Heeke B. Renal insufficiency and the risk of infection from pacemaker or defibrillator surgery. Pacing Clin Electrophysiol. 2006;29(2):142-145. doi:10.1111/j.1540-8159.2006.00307.x
    Article PubMed Google Scholar
11. Lekkerkerker JC, van Nieuwkoop C. Risk factors and time delay associated with cardiac device infections: Leiden device registry. Heart. 2009;95(9):715-720. doi:10.1136/hrt.2008.151985
    Article PubMed Google Scholar
12. Massoure PL, Reuter S, Lafitte S. Pacemaker endocarditis: clinical features and management of 60 consecutive cases. Pacing Clin Electrophysiol. 2007;30(1):12-19. doi:10.1111/j.1540-8159.2007.00574.x
    Article PubMed Google Scholar
13. Sohail MR, Uslan DZ, Khan AH. Infective endocarditis complicating permanent pacemaker and implantable cardioverter-defibrillator infection. Mayo Clin Proc. 2008;83(1):46-53. doi:10.4065/83.1.46
    Article PubMed Google Scholar
14. Rundstrom H, Kennergren C, Andersson R, Alestig K, Hogevik H. Pacemaker endocarditis during 18 years in Goteborg. Scand J Infect Dis. 2004;36(9):674-679.
    PubMed Google Scholar
15. Villamil CI, Rodriguez FM, Van den Eynde CA, Jose V, Canedo RC. Permanent transvenous pacemaker infections: an analysis of 59 cases. Eur J Intern Med. 2007;18(6):484-488.
    PubMed Google Scholar
16. Athan E, Chu VH, Tattevin P. Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices. JAMA. 2012;307(16):1727-1735. doi:10.1001/jama.2012.497
    Article PubMed Google Scholar
17. Ruttmann E, Hangler HB, Kilo J, Höfer D, Müller LC, Hintringer F. Transvenous pacemaker lead removal is safe and effective even in large vegetations: an analysis of 53 cases of pacemaker lead endocarditis. Pacing Clin Electrophysiol. 2006;29(3):231-236. doi:10.1111/j.1540-8159.2006.00328.x
    Article PubMed Google Scholar
18. Chung EH. European consensus document on cardiac implantable electronic device infections. J Am Coll Cardiol. 2020;76(4):494-496.
    PubMed Google Scholar

Additional Information

Publisher’s Note
Bayrakol MP remains neutral with regard to jurisdictional and institutional claims.

Rights and Permissions

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/

View full license details →

About This Article

Received:

January 23, 2023

Accepted:

March 15, 2023

Published Online:

March 23, 2023

Printed:

March 25, 2023