Presented By: Alaa Smadi Rayah AL-qudah Presented By: Alaa Smadi Rayah AL-qudah

What Do I Need to Know? What are the major epidemiologic features of endocarditis and how have they changed? Which bacteria are associated with which types of exposure in the development of endocarditis? What is the pathogenesis of endocarditis and what is its correlation with the different clinical presentations? How is endocarditis diagnosed? What are the basic principles of therapy and prophylaxis?

 Definition : Inflammation of the inner layer of the heart, the endocardium, and usually involves the heart valves.

It is classified depending on whether the microorganism is the source of the inflammation or not into:  Infective endocarditis (IE).  Non- infective endocarditis.  Classification :

NON-INFECTIVE ENDOCARDITIS  Non-Bacterial Thrombotic endocarditis (NBTE), marantice endocarditis.  Characterized by fibrin, platelets and other blood components deposition on the cardiac valves.  the valvular lesions are sterile and don’t contain microorganisms.

Pathogenesis NBTE don’t cause any problem on its own but may be parts of the vegetation break off and embolize to the heart or brain or may be serve as a focus for bacterial colonozation and development of infective endocarditis.

INFECTIVE ENDOCARDITIS Endovascular infection of the cardiovascular structures ( cardiac valves, atrial and ventricular endocardium, large intrathoracic vessels, intracardiac foreign bodies like prosthetic valves and pacemaker)

Classification IE is classified into: 1) Native valve IE 2) Prosthetic valve IE 3) Intravenous drug abuse IE: like narcotic drugs that may introduce an infection which will travel to the right side of the heart, mainly affect the tricuspid valve 4) Nosocomial IE: usually secondary to IV catheters

Acute : Affects normal heart valves Rapidly destructive Commonly Staph. If not treated, usually fatal within 6 weeks Subacute : Often affects damaged heart valves Indolent nature If not treated, usually fatal by one year Other classification:

Epidemiology The incidence varies according to location, but more in developing countries In U.K. : 6-7/ per year, in U.S.A. : 2- 4/ per year. It’s 3 times much more common in males than females.

Pathogenesis of Endocarditis  Inoculation of bacteria colonizing a mucosal (e.g., oral mucosa) or peripheral tissue site into the bloodstream.  Transient bacteremia of a serum-resistant pathogen capable of adhering to a cardiac valvular surface.  Turbulent blood flow across the valve.  Bacterial adherence to cardiac valvular surface.  Pathogen - host tissue interaction resulting in vegetation formation and local tissue damage.  Dissemination of infection to other tissue sites and elicitation of systemic findings

Causes & Source of infection:

 Staphylococci aureus 31%  Viridans group streptococci 17%  Enterococci 11%  Coagulase-negative staphylococci 11% Streptococcus bovis 7 %  Other streptococci 5 %  Non- Hacek gram negative 2%  Fungi 2 %  Culture negative (2-20) %

Rare causes:  HACEK group of organisms 2 % : Haemophilus Actinobacillus Cardiobacterium Eikenella Kingella  Non-HACEK gram-negative bacteria 2%  Fungi 2 %

Risk factors: 1)Structural Heart Disease :  Rheumatic, Aging 2) Artificial heart valves and pacemakers 3) Acquired heart defects  Calcific aortic stenosis  Mitral valve prolapse with regurgitation 4) Congenital heart defects 5) Intravascular catheters 6) Intravenous drug abuse 7) Other infections with bacteremia ( e.g pneumonia, meningitis ) 8) History of infective endocarditis

Clinical presentation  A high index of clinical suspicion is required to identify patients with infective endocarditis and certain criteria should alert the physician.  The clinical presentation of infective endocarditis is dependent on the organism and the presence of predisposing cardiac conditions. Infective endocarditis may occur as an acute, fulminating infection but also occurs as a chronic or subacute illness with low-grade fever and non-specific symptoms.

In patients with infective endocarditis (IE), the present illness history is highly variable. Symptoms commonly are vague, emphasizing constitutional complaints, or complaints may focus on primary cardiac effects or secondary embolic phenomena. Fever and chills are the most common symptoms; anorexia, weight loss, malaise, headache, myalgias, night sweats, shortness of breath, cough, or joint pains are common complaints as well. Primary cardiac disease may present with signs of congestive heart failure due to valvular insufficiency. Secondary phenomena could include focal neurologic complaints due to an embolic stroke or back pain associated with vertebral osteomyelitis. As many as 20% of cases present with focal neurologic complaints and stroke syndromes.

Symptoms : * The onset of symptoms is usually ~2 weeks or less from the initiating bacteremia  Acute IE : High grade fever and chills Arthralgias/ myalgias Pleuritic chest pain Back pain rapid onset of congestive heart failure  Subacute IE : Low grade fever Anorexia Weight loss Fatigue Arthralgias/ myalgias

Pathologic changes Kidney : - immune complex glomerulonephritis - Emboli with infarction - abscess Aortic mycotic aneurysms Cerebral embolism - infarction, abscess, mycotic aneurysm - purulent meningitis “ rare” Splenic enlargement or infarction Septic or bland pulmonary embolism Skin changes

Petechiae  Pinpoint flat round red spots under the skin surface caused by intradermal hemorrhage.  Often located on extremities or mucous membranes.

Osler’s nodes  Diffuse infiltrates of neutrophils, and monocytes in the dermal vessels with immune complex deposition.  Painful and erythematous nodules.  Located on pulp of fingers and toes.  More common in subacute IE.

Janeway lesions  Septic emboli with bacteria, neutrophils, hemorrhage and necrosis  Erythematous, blanching macules  Not painful  Located on palms and soles

Janeway Lesions

Roth spots Retinal haemorrhage with white/pale centers composed of coagulated fibrin.

Complications Cardiac complications n Congestive Heart Failure n Myocardial abscess/pericarditis n Conduction defects can progress to complete heart block. n Myocardial Infarction

Other complications:  Emboli - CNS, Splenic, Lung (Rt sided IE)  Immune-complex glomerulonephritis  Mycotic aneurysms occur at bifurcations - Middle cerebral artery - Adominal aorta - Mesenteric arteries

Etiologies of complications: 1. Embolic 2. Local spread of infection 3. Metastatic spread of infection 4. Formation of immune complexes – glomerulonephritis and arthritis

1-Embolic Complications Emboli consisting of vegetation fragments can occlude or damage virtually any blood vessel, large or small, in the systemic or pulmonary arterial circulation. As a result, emboli can produce: 1-Stroke 2-Painful ischemic or frankly gangrenous extremities 3- Hypoxia (due to pulmonary emboli in right-sided endocarditis) 4- Paralysis (due to embolic infarction of either the brain or spinal cord) 5- Acute myocardial infarction

2- Local spread of infection  Heart failure - Extensive valvular damage  Paravalvular abscess (30-40%) - Most common in aortic valve, IVDA, and S. aureus - May extend into adjacent conduction tissue causing Arrythmias  Pericarditis  Fistulous intracardiac connections

3) Metastatic spread of infection:  Metastatic abscess Kidneys, spleen, brain, soft tissues  Meningitis and/or encephalitis  Vertebral osteomyelitis  Septic arthritis 4) Formation of immune complexes – glomerulonephritis and arthritis

Approach to endocarditis History and Physical examination. Laboratory studies ( blood culture ) Cardiac studies. 1- ECG. 2- Echocardiography. 3- chest radiograph.

Case Definition Several sets of criteria for IE have been described. The most commonly accepted are the revised Duke criteria.

History During the initial assessment of patients with suspected endocarditis, a careful history should be performed with special attention given to a history of prior cardiac lesions and historical clues pointing toward a recent source of bacteremia, such as indwelling intravascular catheters or intravenous drug use.

PHYSICAL EXAMINATION  The physical examination should include a careful cardiac examination for signs of new regurgitant murmurs or heart failure.  A vigorous search should be undertaken for the classic clinical stigmata of endocarditis, including evidence of small and large emboli with special attention to the fundi, conjunctivae, skin, and digits. Associated peripheral cutaneous or mucocutaneous lesions of infective endocarditis (IE) include petechiae, splinter hemorrhages, Janeway lesions, Osler's nodes, and Roth spots.

Investigations : Microbiology: blood culture & serological tests Laboratory tests Electrocardiogram (ECG) Chest X-ray Echocardiograph

Microbiology: Blood culture: Blood cultures should be obtained prior to antibiotic therapy. A minimum of three blood cultures should be obtained over a time period based upon the severity of the illness. If the tempo of illness is subacute and the patient is not critically ill, it is reasonable and often preferable to delay therapy for one to three days while awaiting the results of blood cultures and other diagnostic tests. However, if the patient is acutely ill, three blood cultures should be obtained over a one-hour time span before beginning empiric therapy. Aerobic and anaerobic cultures are required.

Microbiology: Each set of cultures should be obtained from separate venipuncture sites. When blood culture results fail to show an infectious agent after blood is drawn 48 hours after antibiotic therapy has been stopped, the second set of blood for cultures must be drawn approximately 7 days later. If these later culture results remain negative, the diagnosis of IE must be reconsidered.

The interpretation of positive blood cultures in patients with suspected endocarditis is confounded by the fact that false-positive results occasionally occur so it is important to determine if the bacteremia is persistent. The definition of persistent bacteremia varies with the likelihood that the organism is a cause of endocarditis:  For an organism likely to cause endocarditis (eg, S. aureus, viridans streptococci), two positive samples collected more than 12 hours apart.  For an organism that is more commonly a skin contaminant, three or a majority of four or more separate blood cultures are positive and the first and last samples are collected at least one hour apart. Microbiology:

Culture negative endocarditis This accounts for 5–10% of endocarditis cases, the most common cause is prior antimicrobial therapy that can suppress bacterial growth within the vegetation but is insufficient to eliminate the valvular infection or due to a variety of fastidious organisms that fail to grow in normal blood cultures. Currently, with modern automated blood culture systems, fastidious organisms such as nutritionally variant streptococci and members of the HACEK group rarely cause culture-negative IE.  Serological test: Used when diagnosis of IE is suspected and the blood culture are negative.

Laboratory tests: CBC:  Reduced hemoglobin with normochromic normocytic anaemia.  Increased WBCs (leukocytosis).  Increased or reduced platelet. Urea and electrolytes: Renal dysfunction is common in sepsis ( increased urea and creatinine ) Liver biochemistry: Serum alkaline phosphatase may be increased. Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate are increased in any infection. CRP may be useful in monitoring response to therapy (and any relapse).

Urine : Proteinuria and haematuria. Polymerase chain reaction (PCR): may be useful in culture-negative infective endocarditis. Laboratory tests:

Electrocardiogram (ECG): Should be repeated regularly during admission Evidence of MI indicate embloi Atrioventricular block indicate extension of infection to the valve annulus and adjacent septum and abscess Formation Chest X-ray: We should also look for calcification of heart valves.

Echocardiograph :  Echocardiography allows anatomic confirmation of infective endocarditis, sizing of vegetations, detection of intracardiac complications, and assessment of cardiac function.  An echocardiogram should be performed in all patients with a moderate or high suspicion of endocarditis.  Transthoracic echocardiography (TTE) : rapid, non-invasive, sensitivity of 60-75% although the specificity approaches 100 percent, useful in visualization of vegetations and documenting valvular dysfunction and ventricular function and abscesses.  Tranesophageal echocardiography (TEE) : higher sensitivity >90%, useful in suspected aortic root abscess formation, and essential in prosthetic valve endocarditis.  Negative echocardiography doesn’t exclude a diagnosis of endocarditis.

Transthoracic echocardiography Tranesophageal echocardiography

Duke criteria  diagnostic criteria that combine the clinical, microbiological, pathological, and echocardiographic characteristics of a specific case.  The Duke classification relies upon major and minor criteria.  Using the original Duke criteria, cases can be classified as definite, possible, or rejected.

Major Criteria

Minor Criteria

Diagnosis Criteria Definite IE Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess Histologic evidence of vegetation or intracardiac abscess Two major clinical criteria. One major and any three minor clinical criteria. Five minor clinical criteria.

Possible endocarditis: Possible endocarditis is defined as the presence of one major and one or two minor clinical criteria or presence of three minor clinical criteria. Rejected endocarditis A firm alternate diagnosis is made Resolution of clinical manifestations occurs after four days of antibiotic therapy or less No pathological evidence of infective endocarditis is found at surgery or autopsy after antibiotic therapy for four days or less Clinical criteria for possible or definite infective endocarditis not met.

Treatment 1) Antibiotics : Blood culture should be taken prior to empirical antibiotic therapy ( but this should not delay therapy in unstable patient). Antibiotic treatment should continue for 4-6 weeks. Penicillin is fundimental to the therapy of bacterial endocarditis. In patient with penicillin allergy one of the glycopeptide antibiotics, vancomycin or tecoplanin can be used. Serum levels of gentamicin and vancomycin need to be monitored to ensure adequate therapy and prevent toxicity.

Persistent fever Most patient with IE should respond within 48 hours of initiation of appropriate antibiotic therapy this is evidence by a resolution of fever, reduction in serum markers of infection and relief of systematic symptoms of infection. Failure of this may be caused by : 1. Perivalvular extension of infection and possible abscess formation. 2. Drug reaction ( the fever should resolve after drug withdrawal ). 3. Nosocomial infection ( i.e. venous access site, urinary tract infection ). 4. Pulmonary embolism ( secondary right _sided endocarditis or prolonged hospitalization ). In this case samples from all possible sites should be taken and avoid any changing in antibiotic dose or regimen

2) Surgery :  Indications: (1) Refractory CHF, (2) more than one systemic embolus, (3) uncontrolled infection, (4) resistant organisms, (5) perivalvular/myocardial abscess (6) Fungal IE (except that caused by Histoplasma capsulatum) (7) Persistent sepsis after 72 hours of appropriate antibiotic treatment.  Focal neurological deficit is not a contraindication for surgery

Surgical Treatment of Intra- Cardiac Complications Relative indications  Perivalvular extension of infection  Poorly responsive S. aureus NVE  Relapse of NVE  Culture negative NVE/PVE with persistent fever (> 10 days)  Large (> 10mm) or hypermobile vegetation  Endocarditis due to highly resistant enterococcus

Prevention Studies in animal models suggest that antibiotic prophylaxis may be effective. Thus it is possible that rare cases of endocarditis are prevented. Weighing the potential benefits, potential adverse events, and costs associated with antibiotic prophylaxis, the American Heart Association and the European Society of Cardiology now recommend prophylactic antibiotics only for those patients at highest risk for severe morbidity or death from endocarditis.

Prophylaxis proper oral hygiene First and most important – proper oral hygiene Regular dental review Regular dental review Antibiotics only in high-risk group patients – Prosthetic valve or foreign material used for heart repair – History of IE – Congenital heart disease – Use amoxycilin or ampicylin min prior to intervention

Prevention – the procedure Dental procedures known to produce bleeding Tonsillectomy Surgery involving GI, respiratory mucosa Esophageal dilation Gallbladder surgery Cystoscopy, urethral dilation Urethral catheter if infection present Urinary tract surgery, including prostate