1. Infective endocarditis PAULS SĪLIS 29TH OF APRIL 2014.

2. Infective endocarditis (IE)- definition IE is an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect 1. It can also affect prosthetic valves and wires of permanent pacemakers or cardioverter- defibrillators 1,2,3.

3. IE- peculiar disease? 1  The incidence and mortality of IE has not decreased in 30 years  IE presents a variety of different forms, varying according to:  The initial clinical manifestation  the underlying cardiac disease (if any)  the microorganism involved  presence or absence of complications  underlying patient characteristics  guidelines are often based on expert opinion

4. IE- an evolving disease 1  changes in its microbiological profile  higher incidence of:  health care-associated cases  elderly patients  patients with intracardiac devices or prostheses  cases related to rheumatic disease have become less frequent in industrialized nations

5. Epidemiology  The incidence varies from one country to another  ESC 2009: 3–10 episodes/100 000 person-years 1  USA 2009: 12,7 cases per 100 000 persons per year 2  The peak incidence is 14.5 episodes/100 000 person-years in patients between 70 and 80 years of age 1  Mean age in 2009 in USA was 60.8 years 2  Male to female ratio >2:1 1,2,3  The proportion of IE patients with intracardiac devices in the US in 2009 was 18.9%

6. Types of IE 1  according to the site of infection and the presence or absence of intracardiac foreign material:  Left-sided native valve IE  Left-sided prosthetic valve IE  Right-sided IE  Device-related IE (IE developing on pacemaker or defibrillator wires with or without associated valve involvement)

7. Types of IE 1  According to the mode of aquisition:  Community-acquired IE  Health care-associated IE:  Nosocomial- developing >48h after hospitalisation  Non-nosocomial- developing <48h after hospitalisation in a patient with health care contact:  Home-besed nursing or IV therapy, haemodialysis, or IV chemotherapy <30 days before onset  Hospitalised <90 days before onset  Resident of a nursing home or long-term care facility  IE in intravenous drug abusers

8. Types of IE 1  According to microbiological findings:  Infective endocarditis with positive blood cultures: 85% of all IE  Infective endocarditis due to streptococci and enterococci  Staphylococcal infective endocarditis  Infective endocarditis with negative blood cultures because of prior antibiotic treatment (most often oral streptococci or coagulase-negative staphylococci)  Infective endocarditis frequently associated with negative blood cultures- due to fastidious organisms (nutritionally variant streptococci, HACEK group, Brucella, fungi)  Infective endocarditis associated with constantly negative blood cultures- due to intracellular bacteria (Coxiella burnetii, Bartonella, Chlamydia, Tropheryma whipplei)- 5% of all IE

9. Change of etiologic agent  In developing countries, classical patterns persist :  streptococci predominate  most cases of IE develop in patients with rheumatic valve disease  IE cases in developed countries :  increase in the rate of staphylococcal IE  increasing incidence of IE associated with a prosthetic valve

10. Pathophysiology 1,3 : the endothelium  The normal valve endothelium is resistant to colonization and infection by circulating bacteria  The endothelium can by damaged by:  Turbulent blood flow  Electrodes or catheters  Inflammation (as in rheumatic carditis)  Degenerative changes in elderly individuals  Disruption of the endothelium results in exposure of underlying extracellular matrix proteins, the production of tissue factor, and the deposition of fibrin and platelets as a normal healing process  Such nonbacterial thrombotic endocarditis (NBTE) facilitates bacterial adherence and infection

11. Pathophysiology 1,3 : Transient bacteraemia  Both the magnitude of bacteraemia and the ability of the pathogen to attach to damaged valves are important  Bacteraemia occurs:  After invasive procedures, which harm the mucosae of gums, mouth, throat, urethra, GI tract, vagina  as a consequence of chewing and tooth brushing  spontaneous bacteraemia is of low grade and short duration  Viridans streptococci are the main pathogens causing transient bacteraemia, due to extractions of teeth and other stomatologic procedures.

12. Pathophysiology 1,3 : features of the pathogen Classical IE pathogens (S. aureus, Streptococcus spp., and Enterococcus spp.) share the ability to adhere to damaged valves, trigger local procoagulant activity, and nurture infected vegetations in which they can survive. Following colonization, adherent bacteria must escape host defences : ◦Gram-positive bacteria are resistant to complement ◦Bacteria recovered from patients with IE are consistently resistant to platelet microbicidal protein- induced killing

13. Risk populations 3  Patients with :  Prosthetic valves  Episode of IE in the past  Congenital heart defects  Acquired valve disease  Hypertrophic cardiomyopathy  Structural heart diseases affecting the shape or function of ventricles

14. Clinical history The clinical history of IE is highly variable according to the causative microorganism, the presence or absence of pre-existing cardiac disease, and the mode of presentation 1. Symptoms commonly are vague 2. Complaints may include 2 :  Fever (90%) and chills  anorexia,  weight loss,  malaise,  headache,  myalgias,  night sweats,  shortness of breath,  cough,  joint pains  neurologic complaints  back pain  chest pain

15. Physical examination: classic signs 2  Heart murmurs are heard in approximately 85% of patients  Petechiae - Common but nonspecific finding  Subungual (splinter) hemorrhages - Dark red linear lesions in the nailbeds  Osler nodes - Tender subcutaneous nodules usually found on the distal pads of the digits  Janeway lesions - Nontender maculae on the palms and soles  Roth spots - Retinal hemorrhages with small, clear centers; observed in 5% of patients.

16. Emboli

17. Roth spots Oval- shaped, white- centered hemorrhages present on the retina

18. Splinter hemorrhages Small, linear hemorrhages under the nails that are usually asymptomatic

19. Osler’s nodes Painful, erythematous nodules most commonly found on the pads of the fingers and toes

20. Janeway lesion Nontender, erythematous and nodular lesions most commonly found on the palms and soles

21. Physical examination: other signs 2  Stiff neck  Delirium  Paralysis, hemiparesis, aphasia  Conjunctival hemorrhage  Pallor  Gallops  Rales  Cardiac arrhythmia  Pericardial rub  Pleural friction rub

22. *NB: Fever may be absent in the elderly, after antibiotic pre-treatment, in the immunocompromised patient and in IE involving less virulent or atypical organisms. Table 7: Clinical presentation of infective endocarditis. «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p10.

23. Echocardiography 1  Echocardiography must be performed rapidly, as soon as IE is suspected.  Echocardiography has a fundamental importance in diagnosis, management, and follow-up of IE.  Three echocardiographic findings are major criteria in the diagnosis of IE: vegetation, abscess, and new dehiscence of a prosthetic valve.  Other findings may include: pseudoaneurysm, perforation, fistula, valve aneurysm Figure 1 Indications for echocardiography in suspected infective endocarditis. «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p11.

24. Vegetations

25. Microbiological diagnosis 1  Blood cultures:  Positive blood cultures remain the cornerstones of diagnosis  They provide live bacteria for susceptibility testing  3 sets (including at least one aerobic and one anaerobic) drawn at 30 min intervals obtained prior to antibiotic administration is usualy sufficient to identify the usual microorganisms  Pathological examination of resected valvular tissue or embolic fragments remains the gold standard for the diagnosis of IE  The polymerase chain reaction (PCR) allows rapid and reliable detection of fastidious and non- culturable agents  Electron microscopy has high sensitivity and may help to characterize new microorganisms  Serological testing using indirect immunofluorescence or enzyme-linked immunosorbent assay (ELISA) can be used to identify some microorganisms

26. Modified Duke criteria Table 11 Modified Duke criteria for the diagnosis of infective endocarditis. «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p11.

27. Potential complications of IE 2  Congestive heart failure (50–60% of cases overall)  Arterial emboli (20–50% of cases)  Cardiac valvular insufficiency  Myocardial infarction, pericarditis, cardiac arrhythmia  Sinus of Valsalva aneurysm  Aortic root or myocardial abscesses  Infarcts, mycotic aneurysms  Arthritis, myositis  Glomerulonephritis, acute renal failure  Stroke syndromes  Mesenteric or splenic abscess or infarct

28. Empirical therapy 1  Treatment of IE should be started promptly  The initial choice of empirical treatment depends on:  whether the patient has received prior antibiotic therapy or not  whether the infection affects a native valve or a prosthesis  knowledge of local epidemiology, especially for antibiotic resistance  Drug treatment of prosthetic valve endocarditis should last longer (at least 6 weeks) than that of native valve endocarditis (2–6 weeks)

29. Empirical treatment Table 17 Proposed antibiotic regimens for initial empirical treatment of infective endocarditis. (before or without pathogen identification). «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p22.

30. Indications for surgery  Surgical treatment is used in approximately half of patients with IE because of severe complications  Surgery is justified in patients with high-risk features which make the possibility of cure with antibiotic treatment unlikely and who do not have co-morbid conditions or complications which make the prospect of recovery remote  The three main indications for early surgery (while the patient is still receiving antibiotic treatment) in IE are heart failure, uncontrolled infection, and prevention of embolic events  In Latvia, the need for sugery is discussed with a cardiac surgeon in every case of IE.

31. Table 19 Indications and timing of surgery in left-sided native valve infective endocarditis «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p23.

32. Prognosis 1  The in-hospital mortality rate of patients with IE varies from 9.6 to 26%  The mortality rate differs considerably from patient to patient  Patients with heart failure (HF), periannular complications, and/or S. aureus infection are at highest risk of death and need for surgery in the active phase of the disease  When three of these factors are present, the risk reaches 79%  Approximately 50% of patients undergo surgery during hospitalization.  Patients with an indication for surgery who cannot proceed due to prohibitive surgical risk have the worst prognosis

33. Predictors of poor outcome Table 12 Predictors of poor outcome in patients with IE. «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p15.

34. Recurrence 1  Relapse- repeat episode of IE caused by the same microorganism <6 months after the initial episode  Reinfection  Infection with a different microorganism  Repeat episode of IE caused by the same microorganism >6 months after the initial episode  Patients should be educated about the signs and symptoms of IE after discharge

35. Prophylaxis 1  Antibiotic prophylaxis should only be considered in patients at high risk of IE:  Patients with a prosthetic valve or prosthetic material used for cardiac valve repare,  Patients with previous IE  Patients with congenital heart disease  Antibiotic prophylaxis should only considered for dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa

36. Prophylaxis: antibiotics 1  The main targets for antibiotic prophylaxis are oral streptococci Table 6 Recommended prophylaxis for dental procedures at risk. «Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)» p9.

37. References 1.The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009) 2.John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD, Barry E Brenner, MD, PhD, FACEP et al. Infective Endocarditis http://emedicine.medscape.com/article/216650-overviewhttp://emedicine.medscape.com/article/216650-overview 3.A. Lejnieks, I. Ādamsone,. Beķeris et al. «Prfesora Aivara Lejnieka redakcijā, Klīniskā medicīna, Pirmā grāmata», SIA Medicīnas apgāds Rīgā, 2010. 318-340. lpp.