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Endocarditis & Infections of the Heart Nausheen Akhter, MD Core Curriculum March 4, 2008 Contents Epidemiology and Microorganisms Pathophysiology Clinical Features Diagnosis and Treatment Prevention and Guidelines Other Infections: Bacterial Pericarditis, Infected Devices Infective Endocarditis (IE) IE is an infection of the endothelial lining of the heart valves, mitral or tricuspid chorda tendinea, valve annulus, and aortic root. Pre-existing heart disease is found in 2/3 of the cases of left-sided IE. 1/3 patients have normal or clinically unrecognized valve disease. 3.6 to 7.0 cases/100,000 patient-years Epidemiology Predisposing Conditions RHD CHD MVP DHD IVDU Other None Adults (%) 15 - 60 yr > 60 yr 25-30 10-20 8 2 10-30 Rare 15-35 10-15 10 30 10 10 25-45 25-40 Braunwald 8th Edition Epidemiology Who is at high risk for developing endocarditis? People with prosthetic heart valves, previous incidents of endocarditis, complex congenital heart disease, IVDU, and surgically devised systemic pulmonary shunts. What patients have a moderate risk for developing endocarditis? Acquired valvular dysfunction, HCOM, and uncorrected congenital defects. Zevitz, M. Pearls of Wisdom Board Review Epidemiology Patient Populations MVP (7-30% of NVE not related to IVDU or nosocomial infection) Risk is mostly in pts with thickened valve leaflets (>5mm) and MR murmur. MVP + murmur 52/100,000 vs. no murmur 4.6/100,000 personyr RHD MV > AV CHD (10-20% young adults, 9% older adults) PDA, VSD, and biscupid aortic valve most common HIV Not significant risk for IE, unless IVDU Braunwald 8th Edition Epidemiology Patient Populations IVDU (2-5%/patient-year) TV>MV>AV=multiple sites TV IE is associated with pleuritic chest pain, SOB, cough, and hemoptysis. CXR may have septic pulmonary emboli. IVDU is a risk factor for recurrent NVE HIV, 27 to 73% of IVDU with IE, risk and mortality is inversely related to CD4 counts. Braunwald 8th Edition Epidemiology Patient Populations Prosthetic Valve Endocarditis (PVE) 10 to 30% of all IE in developed countries “Early” PVE, symptoms within 60 days, occurs at greater frequency than “late” 0-12 months, PVE in mechanical > bioprosthetic >12 months, PVE bioprosthetic > mechanical By 5 years, PVE bioprosthetic = mechanical Braunwald 8th Edition Epidemiology Patient Populations Health care-associated Nosocomial and community-acquired as a consequence of indwelling devices HD is independently associated with S. aureus. Catheter-associated S. aureus bacteremia is the predominant risk factor for IE in this group. Treat as presumed IE, if persistent fever or bacteremia for 4 days after catheter removed. Braunwald 8th Edition Distribution of Types of IE Isolated AV IE is observed in 55-60% of cases. Isolated MV IE occurs in 25-30% of cases. IE of both valves occurs in 15% of cases. Prosthetic valve IE constitutes 10-25% of all cases of IE. Prosthetic valve IE is more common with prosthetic AV, multiple valves, and after replacement of an infected native valve Roldan CA. The Ultimate Echo Guide Distribution of Types of IE Right-sided IE constitutes 5-10% of all cases. 80% TV is involved Most commonly associated with IVDU Also occurs in patients with right heart wires or catheters. What is the incidence of culture-negative endocarditis? 5-10% Roldan CA. The Ultimate Echo Guide Microorganisms NEJM 345 (18), 2001 Microorganisms What is the most common organism associated with endocarditis? Streptococcus viridans What organisms are most frequently implicated in endocarditis of IVDU? Gram negative, fungal and S. Aureus Fungi cause what percentage of PVE? 15% What is the most frequent organism reported with myocardial abscess? S. Aureus Zevitz, M. Pearls of Wisdom Board Review Microorganisms History of contact with mammals and/or birds may suggest infection by what organisms? Coxiella burnetii (Q fever), Brucella species or Chlamydia psittaci A nosocomial cluster of cases postoperatively may be caused by what organisms? Legionella or Mycobacterium species What organism, once accounted for 25% of cases, now only 1-2% of cases? Neisseria gonorrhoeae Zevitz, M. Pearls of Wisdom Board Review Pathophysiology It is hypothesized that platelet-fibrin deposition occurs spontaneously on abnormal valves and at sites of cardiac endothelium injury or inflammation and that these deposits are called nonbacterial thrombotic endocarditis (NBTE). NBTE are the sites at which microorganisms adhere during bacteremia to initiate IE. 2 mechanisms in the formation of NBTE: Endothelial injury Hypercoagulable state. 3 hemodynamic circumstances that may initiating NBTE: (1) a high-velocity jet striking endothelium; (2) flow from a high- to a lowpressure chamber; and (3) flow across a narrow orifice at high velocity. Braunwald 8th Edition Pathophysiology Bacteremia converts NBTE to IE. Bacteremia rates are highest for trauma of the oral mucosa (especially gingiva), than GU, and GI tract. Braunwald 8th Edition Braunwald 8th Edition Clinical Features Destructive effects of intracardiac infection Embolization of septic fragments of vegetations to distant sites causing infarction/infection Hematogenous seeding of remote sites An antibody response with subsequent tissue injury caused by deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues. Braunwald 8th Edition Braunwald 8th Edition Symptoms % of Pts Signs % of Pts Fever 80-85 Fever 80-90 Chills 42-75 Murmur 80-95 Sweats 25 Changing M 10-40 Anorexia 25-55 Neuro abn 30-40 Wt loss 25-35 Emboli 20-40 Malaise 25-40 Splenomeg 15-50 Dyspnea 20-40 Clubbing 10-20 Cough 25 Peripheral manifestations Stroke 13-20 Osler nodes 7-10 H/A 15-40 Splinters 5-15 N/V 15-40 Petechiae 10-40 Myalgia/Arthral. 15-30 Janeway lesion 6-10 Chest pain 8-35 Roth spots 4-10 Braunwald 8th Edition Clinical Features What signs and symptoms are associated with a myocardial abscess? Low-grade fevers, chills, leukocytosis, conduction system abnormalities, nonspecific ECG changes and sign/sx of acute MI Osler’s nodes are usually nodular and painful. True What other conditions are associated with Osler’s nodes? NBTE, gonococcal infection and hemolytic anemia Zevitz, M. Pearls of Wisdom Board Review Diagnosis: Duke’s Criteria AHA/ACC Valve Guidelines 2006 Diagnosis TTE sensitivity Vegetation <5mm 25% Between 6-10mm 70% TEE sensitivity 90-100% Prosthetic endocarditis TEE >> TTE Evangelista Heart 90: 614-617 (2004) Diagnosis Class I Indications for Echocardiography in IE of Native and Prosthetic Valves: Detection and characterization of valvular lesions, hemodynamic severity, and ventricular compensation Detection of vegetations and characterization of lesions in patients with CHD Detection of abscess, perforation or fistulas Reevaluation studies in patients with complex endocarditis In patients with highly suspected culture-negative IE Evaluation of bacteremia without a known source in a patient with a prosthetic valve. Roldan CA. The Ultimate Echo Guide Diagnosis Positive Echo findings: Presence of vegetations defined as mobile echodense masses implanted in a valve or mural endocardium in the trajectory of the regurgitant jet or implanted in prosthetic material with no alternative anatomical explanation Presence of abscess defined as definite region of reduced echo density, or echolucent cavities within annulus or adjacent myocardial structures New dehiscence of valvular prosthesis Roldan CA. The Ultimate Echo Guide Braunwald 8th Edition BMJ Vol. 333, Aug. 2006 Evangelista Heart 90: 614-617 (2004) Detection of Complications Valve perforation Valvular, annular, or aortic root, or myocardial abscess Valve psuedoaneurysm Fistulas Ring dehiscence Valvular regurgitation PVE commonly extends beyond the valve ring into the annulus which can cause dehiscence, paravalvular regurgitation and conduction disturbances. Braunwald 8th Edition BMJ Vol. 333, Aug. 2006 Evangelista Heart 90: 614-617 (2004) BMJ Vol. 333, Aug. 2006 Subaortic Complications of AV Endocarditis “TEE Recognition of Subaortic Complicatons in AV endocarditis” Karalis DG, et al. (Circulation 1992; 86: 353 – 362). May 1988 – August 1991, 55 consecutive patients 44% (N = 24) had subaortic complications. Secondary involvement of the mitral-aortic intervalvular fibrosa (MAIVF) and the anterior mitral leaflet (AML) Direct extension of infection and/or less commonly the infected AI jet striking the subaortic structures Abscess, aneurysm, perforation Subaortic Complications of AV Endocarditis Subaortic Complications of AV Endocarditis Subaortic Complications of AV Endocarditis Subaortic Complications of AV Endocarditis Subaortic Complications of AV Endocarditis Subaortic Complications of AV Endocarditis Secondary infections of the subaortic structures may be more common than appreciated. The MAIVF and AML should be investigated in all patients with AV endocarditis. Thickening of the posterior aortic root or AML with an eccentric MR color jet should alert to possible subaortic complications. Differential Diagnosis of IE Valve excrescences Ruptured chordae tendinea Torn bioprosthetic leaflet Libman-Sacks endocarditis Rheumatic valvulitis NBTE Papillary fibroelastoma Libman-Sacks Endocarditis Rheumatic Valvulitis Google Images Papillary Fibroelastoma Ruptured chordae tendinea Google Images Medical Therapy NEJM 345 (18), 2001 Indications for Valve Surgery Endocarditis-related valvular heart failure (mortality 56 – 86%) Moderate to severe CHF (NYHA III or IV) No control of infection, difficult-to-treat microbes Embolic risk (vegetation length > 15mm strong predictor of new EE and mortality) Neurologic complications Perivalvular infection/abscess Valvular obstruction Unstable prosthesis Prosthetic infective endocarditis (esp. S. Aureus) Fungal infective endocarditis Circulation 2005; 112: 69-75 JACC 2001; 37: 1069 Prevention/Guidelines Wilson, et al. Circulation. 2007; 115 Rationale IE prophylaxis regimen has been evolving for the past 50 years. Basis for recommendations and quality of evidence limited to expert opinion, small trails [Class IIb, LOE C] Several assumptions have led to development of abx prophylaxis in humans, and these assumptions have been recently questioned Wilson, et al. Circulation. 2007; 115 Rationale AHA/ACC guidelines have become overly complicated and wrought with ambiguities, making interpretation difficult for practitioners. Potential consequences of changes include: altering established practice, decreasing pts eligible for prophylaxis, decreasing malpractice suits and spurring more trials Wilson, et al. Circulation. 2007; 115 Evidence (1) Frequency, nature, magnitude, and duration of bacteremia associated with dental procedures (2) Impact of dental disease, oral hygiene, and type of dental procedure on bacteremia (3) Impact of antibiotic prophylaxis on bacteremia from a dental procedure (4) The exposure over time of frequently occurring bacteremia from routine daily activities compared with bacteremia from various dental procedures. Wilson, et al. Circulation. 2007; 115 Evidence Dental procedures Transient bacteremia is common with manipulation of the teeth and periodontal tissues. Wide variation in reported frequencies of bacteremia in patients resulting from dental procedures: Tooth extraction (10% to 100%), Periodontal surgery (36% to 88%), Teeth cleaning (up to 40%) Endodontic procedures (up to 20%) Wilson, et al. Circulation. 2007; 115 Evidence Routine daily activities Unrelated to a dental procedure Tooth brushing and flossing (20% to 68%) Use of wooden toothpicks (20% to 40%) Use of water irrigation devices (7% to 50%) Chewing food (7% to 51%) Wilson, et al. Circulation. 2007; 115 Evidence Few published studies exist on the magnitude of bacteremia after a dental procedure or from routine daily activities, and most of the published data used older, often unreliable microbiological methodology. There are no published data that demonstrate that a greater magnitude of bacteremia, compared with a lower magnitude, is more likely to cause IE in humans. Wilson, et al. Circulation. 2007; 115 Evidence The magnitude of bacteremia resulting from a dental procedure is relatively low, similar to that resulting from routine daily activities, and is less than that used to cause experimental IE in animal. Although the infective dose required to cause IE in humans is unknown, the number of microorganisms present in blood after a dental procedure or associated with daily activities is low. Wilson, et al. Circulation. 2007; 115 Dental Recommendations The vast majority of cases of IE caused by oral microflora most likely result from random bacteremias caused by routine daily activities, such as chewing food, tooth brushing, flossing, use of toothpicks, use of water irrigation devices, and other activities. The presence of dental disease may increase the risk of bacteremia associated with these routine activities. There should be a shift in emphasis away from a focus on a dental procedure and antibiotic prophylaxis toward a greater emphasis on improved access to dental care and oral health in patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE and those conditions that predispose to the acquisition of IE Wilson, et al. Circulation. 2007; 115 GI/GU Recomendations The possible association between GI or GU tract procedures and IE has not been studied as extensively as the possible association with dental procedures. The administration of prophylactic antibiotics solely to prevent endocarditis is not recommended for patients who undergo GI or GU procedures, including EGD or colonoscopy. Wilson, et al. Circulation. 2007; 115 Summary of Major Changes Wilson, et al. Circulation. 2007; 115 Highest Risk Patients Wilson, et al. Circulation. 2007; 115 Regimans Wilson, et al. Circulation. 2007; 115 Bacterial Pericarditis Bacterial pericarditis is not synonymous with purulent pericarditis. 50% have classic signs: chest pain, rub, pulsus Staph and strep are the most common organisms, 22-31% Sources: Lung 40%, hematogenous 22-29%, trauma 24-29%, endocarditis/abscess 14-22% Pankuweit S et al. Bacterial Pericarditis, Diagnosis and Management. Am J Cardiovasc Drugs 2005; 5(2): 103-112. Bacterial Pericarditis Purulent pericarditis is fatal if untreated, 40% mortality. TB Pericarditis: Effusive-contrictive (30-50%) 85% mortality if left untreated. Pericardial biopsy is more sensitive than pericardiocentesis (100% vs 33%) AIDS Pericarditis: Leading cause of infectious pericarditis 35% MAI Pankuweit S et al. Bacterial Pericarditis, Diagnosis and Management. Am J Cardiovasc Drugs 2005; 5(2): 103-112. Bacterial Pericarditis Management: First emperic antibiotic therapy (anti-staph and aminoglycoside), then tailor therapy. Open surgical drainage is preferred. Rinsing pericardium with antibiotics, urokinase/ streptokinase may help clear infection. Pericardiotomy is recommended for recurrent effusions. Pankuweit S et al. Bacterial Pericarditis, Diagnosis and Management. Am J Cardiovasc Drugs 2005; 5(2): 103-112. Echo Findings of Constriction 1) Increased pericardial thickness and occasionally calcification TEE measurement correlates with CT 2) Septal shudder/bounce 3) RV/LV inflow – increased E velocity Due to early rapid diastolic filling 4) Tissue doppler – prominent E velocity Major difference between constriction and restriction 5) Other: IV/hepatic v. dilation, biatrial enlargement Roldan CA. The Ultimate Echo Guide Echo Findings of Constriction UptoDate: Hemodynamics of Constrictive Pericarditis vs Restrictive Cardiomyopathy Device Infections The Prospective Evaluation of Pacemaker Lead Endocarditis study is a multicenter, prospective survey of the incidence and risk factors of infectious complications after implantation of pacemakers and cardioverterdefibrillators. January 1 - December 31, 2000, 6319 consecutive recipients of implantable systems were enrolled at 44 medical centers and followed up for 12 months. Infections developed over 12 months in 42 patients, incidence of 0.68/100 patients. Circulation, Sept. 2007, 116: 1349-1355 Conclusions The epidemiology of IE has changed in developed countries. TEE has a 95% sensitivity in detecting vegetations and is also key in finding complications of vegetations. Moderate to severe heart failure and vegetation length are important indications for surgery. Antibiotic prophylaxis regiman for IE was updated in 2007. Questions/Comments??