176 CHAPTER 3 Valvular heart disease Tricuspid and pulmonary disease Tricuspid regurgitation Causes: Functional or secondary TR (normal lea \202 ets, RV annular dilatation due to MV disease, congenital heart disease) i s common. Organic tricuspid lesions: endocarditis most common (particularly intravenous (IV ) drug abuse), transvalvular pacing wires, Marfan \200\231s syndrome, Ebstein anomaly, rheu matic heart disease, carcinoid. Clinical features: Usually minimal. Peripheral oedema, ascites, nausea, anorexia, abdominal pain (tender, congested liver) are late signs. Physical examination: Cachexia/wasting, jaundice, oedema, AF common, elevated JVP with syst olic CV waves, tender pulsatile hepatomegaly. Auscultation \200\224 RV S 3 often heard ( i in inspiration), presystolic murmur (PSM) audible at left sternal edge (LSE) ( i in inspir ation). Murmur loudest in TR secondary to pulmonary hypertension. Investigations: ECG \200\224 non-speci \201 c, may show evidence of underlying condition. CXR \200\224 cardiomegaly in patients with functional TR, occasionally distended azygos v ein, pleural effusion. TTE \200\224 color Doppler con \201 rms diagnosis. CW Doppler of T R jet can assess PA systolic pressure. Two- dimensional (2D) images can give idea of cause of TR (RV infarction, ventricular septal defect (VSD), Ebstein, etc.) Severe TR \200\224 j et width > 0.7 cm and systolic \202 ow reversal in hepatic veins. Treatment \200 In the absence of pulmonary hypertension, TR is well tolerated and may not require speci \201 c treatment (indeed in SBE of TV, valve excision is sometimes p erformed with good recovery). Symptoms of RV failure respond to diuretics and \202 uid/salt restriction. \200 If co-e xistent MV disease is being operated on and TR is mild (with normal PA pressure), TR may improve postoperatively as PA pressure falls. TV annuloplasty is indicated in patients undergoing MVR with severe or moderate TR and annular dilatation or pulmonary hypertension. TR secondary to valve pathology (Ebstein, carcinoid) may require valve replacement, prefera bly with a large bioprosthesis to minimize the risk of thrombosis (but high operative morta lity 15 % ). Tricuspid stenosis Causes: Rheumatic heart disease (almost always associated with MS), cong enital, carcinoid, pacemaker lead. Extremely rare. Clinical features: Fatigue, anorexia, peripheral oedema. Physical examination: Wasting, oed ema, hepatomegaly, i JVP, prominent \200\230a \200\231 waves, rumbling mid-diastolic murmu r at LLSE in inspiration. Investigations: ECG \200\224 sinus rhythm with signs RA enlargem ent ( i \200\230P \200\231 waves in II, V 1 \200\224 often coincides with signs of LA enl argement because of MS) but no RVH. CXR \200\224 enlarged RA but normal PA size. TTE \200 \224 2D image can show thickened restricted lea \202 ets. CW Doppler is diagnostic. Severe TS \200\224 valve area <1.0 cm 2 . Look for co-existent MS. TRICUSPID AND PULMONARY DISEASE 177 Management: Salt restriction and diuretics. If co-existent MS is being operated on then sur gical valvuloplasty may help. TV replacement is occasionally performed. Bioprosthetic valve s give better results than mechanical valves. There is recent evidence of usefulness of TV balloon valvuloplasty but use remains controversial. Pulmonic stenosis Causes: Congenital (virtually all), carcinoid, rheumatic, compression. Clinical features: Usually none. If longstanding severe stenosis \200\224 exertional dyspn oea, light-headedness/syncope (inability to i CO). Ultimately may develop TR symptoms of RV failure (see previous). Physical examination: Prominent \200\230a \200\231 wave in JVP, RV heave, occasionally thr ill in 2nd left intercostal space. Auscultation \200\224 widely split S 2 (as pulmonary va lve (PV) closure becomes later), P 2 becomes softer (unless stenosis is supravalvular), eje ction systolic murmur (ESM) at left edge of upper sternum, heard best in inspiration. Investigations: ECG \200\224 RVH and RA enlargement. CXR \200\224 dilated pulmonary arter ies, occasionally with calci \201 cation of valve, if severe then oligaemic lung \201 el ds. TTE \200\224 con \201 rms diagnosis and can show level of stenosis (valvular, suprava lvular or RV out \202 ow tract) and severity. Severe pulmonic stenosis (PS): jet velocity > 4 m/s or max gradient > 60 mmHg. Will also show associated conditions (ASD, patent ductus arteriosus (PDA), Fallot \200\231s, etc). Cardiac catheterization \200\224 to assess seve rity of obstruction and haemodynamic effects. Management: In general, invasive intervention is recommended when gradient across valve is > 40 mmHg at rest or when symptoms occur. Medical \200\224 supportive/symptomatic treatmen t of RV failure, diuretics, \202 uid restriction (cautious). Balloon valvuloplasty \200 \224 treatment of choice for stenosis at valvular level. Highly effective, safe with good l ong-term results. Pulmonary regurgitation (PR) is common following valvuloplasty, but is ra rely clinically important. Surgical \200\224 valvotomy is very effective with minimal recu rrence. Pulmonic valve replacement \200\224 indicated if not suitable for above treatments or for severe PR following these treatments. Pulmonary regurgitation Causes: Any cause of pulmonary hypertension (causes dilatation of v alve ring), infective endocarditis, connective tissue disease (e.g. Marfan \200\231s), iatr ogenic (following valvotomy or PA catheter placement), carcinoid. Clinical features: Often asymptomatic. Symptoms occur when pulmonary hypertension or RV fai lure exist. Then patients get dyspnoea on exertion, lethargy, peripheral oedema, abdominal pain. Physical examination: RV heave, occasionally a thrill in pulmonary area. Auscultation \200 \224 P 2 may be delayed (large SV), loud (if pulmonary i BP), or soft (if PV stenosis). Mur mur of PR heard best in 3rd/4th intercostal space on left adjacent to sternum, I during ins piration. 178 CHAPTER 3 Valvular heart disease Investigations: ECG \200\224 RVH (if pulmonary i BP), right bundle branch block (RBBB)/rsR pattern in V 1 . CXR \200\224 enlarged PA and RV. TTE \200\224 2D images may show RV dil atation/hypertrophy. Abnormal septal motion if RV volume overload. PR seen on color Doppler and quanti \201 ed with pulsed Doppler. Severe PR \200\224 color jet \201 lls out \202 ow tract. Management: Usually supportive treatment suf \201 ces. Treat RV failure in usual way (diur etics, etc). If PR is due to PV ring dilatation secondary to pulmonary hypertension, treati ng the underlying cause of pulmonary i BP can decrease the severity of PR (e.g. mitral valv e surgery). If there is symptomatic right heart failure with severe PR, then PV replacement should be considered. Indications for PVR in asymptomatic individuals remain unclear. This page intentionally left blank 180 CHAPTER 3 Valvular heart disease Prosthetic heart valves Types See Fig. 3.5 . Mechanical: Bilea \202 et (St Jude Medical , Carbomedics ) most common today. Ball and cage (Starr \200\223Edwards ) or tilting disc (Medtronic Hall ) Bioprosthetic: Porcine (stented or stentless) or bovine pericardium (Carpentier \200\223Edw ards) Non prosthetic valves: Homograft (preserved cadaveric human valve), autograft (pulmonary va lve \200\224 Ross procedure) Mechanical valves Minimal risk of structural failure. Lifetime risk of reoperation for non- structural valve dysfunction around 5 % . Thrombogenic, therefore requiring lifelong warfa rin therapy ( aspirin if high risk). Even with optimal INR, there is 2 \200\2234 % linea rized annual lifetime risk of major thromboembolic or haemorrhagic events, including stroke . Tissue valves (Bioprosthetic or homograft) do not require anticoagulation but are not as du rable as mechanical valves (15-year failure rate of 5 \200\22320 % for biopros- theses depe nding on patient age \200\224 best durability in older patients). 0.5 % linnearized annula r risk of thromboembolism. More likely to have post- operative gradient than mechanical val ves in smaller sizes. Valve haemodynamics Different prosthetic valves have unique pro \201 les and effective ori \201 ce area. For any given valve dimension, bioprosthetic valves have the smallest effec tive ori \201 ce area and bilea \202 et valves the best. Assessment of prosthetic valve function Clinically: Each prosthetic valve produces a distin ctive sound. Dysfunction may be indicated by new sounds, a change in sound or volume of sou nd, or a new (or changing) murmur. Imaging modality: Fluoroscopy can be used to assess valve lea \202 et movement (in mechani cal valves). Diminished motion in thrombosis, excessive movement of base ring if valve dehi sced. TTE \200\224 limited use because of ECHO shadow caused by metal in valve. Can be use d to look at valve ring motion (in mechanical valves), lea \202 et motion (in tissue valve s), and regurgitation (with Doppler). TOE \200\224 better at assessing prosthetic mitral v alve function but less good at prosthetic aortic valve assessment. Magnetic resonance imagi ng (MRI) \200\224 safe in majority of modern mechanical valves. Expensive and time consumi ng, therefore reserved for cases when TTE/TOE is inconclusive. Cardiac catheterization: Can assess valve gradient (and therefore valve area). Can quantify degree of regurgitation. Risk of passing catheter across mechanical valves; therefore used prior to reoperation or when non- invasive tests are inconclusive. PROSTHETIC HEART VALVES 181 Fig. 3.5 Common types of heart valve prostheses (from top left clockwise): St Jude \200\231 s Medical bilea \202 et, Starr \200\223Edwards ball and cage, Bjork \200\223Shiley tilting disk, stented porcine prosthesis. Reproduced with permission from Bloom \201 eld P (2002). Heart 87 : 583 \200\2239. Choice of the prosthesis: in favor of mechanical prosthesis a \200 Desire of the informed patient and absence of contraindication for long-term anticoagulation Patients at risk of accelerated structural valve deterioration b \200 Patients already on anticoagulation because of other mechanical prosthesis Patients already on anticoagulation because at high risk for thromboembolism c Age <65 \200\22370 years and long life expectancy d \200 Patients for whom future redo va lve surgery would be at high risk (due to LV dysfunction, previous CABG, multiple valve pro sthesis). a The decision is based on the integration of several of the factors given in the table. b Young age, hyperparathyroidism. c Risk factors for thromboembolism: severe LV dysfunction, atrial \201 brillation, previous thromboembolism, hypercoagulable state. d According to a ge, sex, the presence of co-morbidity, and country-speci \201 c life expectancy. Adapted from European Society of Cardiology (ESC) (2007). Guidelines on the Management of V alvular Heart Disease: The Task Force on the Management of Valvular Heart Disease of the Eu ropean Society of Cardiology. Eur Heart J 28 : 230 \200\22368. Y http://www.escardio.org/gu idelines- surveys/esc-guidelines/GuidelinesDocuments/guidelines-VHD-FT.pdf 182 CHAPTER 3 Valvular heart disease Choice of the prosthesis: in favor of bioprosthesis a \200 Desire of the informed patient \200 Unavailability of good-quality anticoagulation (contraindication or high risk, unwi llingness, compliance problems, lifestyle, occupation) Reoperation for mechanical valve thrombosis in a patient with proven poor anticoagulant control Patient for whom future redo valve surgery would be at low risk \200 Limited life expecta ncy b , severe co-morbidity, or age > 65 \200\22370 years \200 Young woman contemplating pregnancy. a The decision is based on the integration of several of the factors given in th e table. b According to age, sex, the presence of co-morbidity, and country-speci \201 c l ife expectancy. Adapted from European Society of Cardiology (ESC) (2007). Guidelines on the Management of V alvular Heart Disease: The Task Force on the Management of Valvular Heart Disease of the Eu ropean Society of Cardiology. Eur Heart J 28 : 230 \200\22368. Y http://www.escardio.org/ g uidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-VHD-FT.pdf. This page intentionally left blank 184 CHAPTER 3 Valvular heart disease Prosthetic valve complications Valve thrombosis Incidence: 0.1 \200\2235.7 % per patient-ye ar; <0.01 % per day if anticoagulation withheld (may be necessary for life-threatening blee d). Risks: Inadequate anticoagulation and mitral prostheses. Ball and cage valve at lower risk as occluder travels completely out of housing. Bilea \202 et valve can continue to work pa rtially, but single lea \202 et may fail catastrophically. Clinical presentation: Pulmonary oedema, embolization, sudden death. Investigation: d inten sity of valve sounds, d movement of lea \202 ets on TTE or \202 uoroscopy (and i valve g radient on TTE). Treatment: Anticoagulation with heparin. If thrombus is <5 mm on TTE, then anticoagulation may suf \201 ce. If > 5 mm then will need further treatment (thrombolysis , thrombectomy or valve replacement). High recurrence rate if valve not replaced. Prognosis: Valve replacement for valve thrombus has mortality rate of <15 % , thrombolysis has mortality rate of <10 % (with embolization in <20 % ). Thrombolysis may be more effecti ve for aortic valve thrombosis and in recent (<2 week) onset. Embolization Most manifest as cerebral infarctions. Incidence: In unanticoagulated patients 5 % per patient-year (causing death or stroke), 1 \200\2232 % per patient-year on therapeutic anticoagulation Risks: AF, age > 70 years, d LV function, mitral prostheses, ball and cage valves, > 1 valve. Consider endocarditis in pat ients with prosthetic valves presenting with peripheral embolization. If cerebral embolizat ion, perform immediate computed tomography (CT) to exclude bleed (if bleed con \201 rmed, withhold anticoagulation and seek specialist help). Haemolysis A low level of background haemolysis is common in patients with mechan- ical pro stheses (even when functioning normally). Severe haemolysis is uncommon and is usually seco ndary to valve dysfunction (leakage, dehis- cence, infection). Investigation: d hemoglobin (Hb), i lactate dehydrogenase (LDH), d serum haptoglobin level, reticulocytosis. Treatment: Treat underlying problem (including further valve surgery), blood transfusion, folic acid, ferrous sulfate. Occasionally re-replacement is required for cases requiring frequent bloo d transfusion. Endocarditis (see b Coronary artery disease, Chapter 5, p. 211) Prevalence: Lifetime risk a round 3 \200\2236 % of patients with prosthetic valves. Early endocarditis cases occur with in 60 days of valve surgery, and late endocarditis occurs > 60 days since surgery. Early pr osthetic valve PROSTHETIC VALVE COMPLICATIONS 185 endocarditis (PVE) usually arises from skin/wound infections or from indwelling IV cannulae . Commonly due to S. aureus , S. epidermidis , Gram- negative bacteria, and fungi. Late PVE has similar organisms as native valve endocarditis (mainly streptococci). Similar risk for tissue and mechanical valves. Structural valve degeneration and reoperation Incidence: Structural valve degeneration (SVD ) is inevitable for all currently available bioprosthetic valves if the patient lives long enough. Valves calcify, lea \202 ets tear, resulting in regurgitation stenosis. \200 Freedom from SVD 8 90 % at 12 years, for AVR in 60 year old, decreasing rapidly beyond 15 years of follow-up. Freedom from reoperation for 2nd-generation bioprostheses > 90 % at 10 years, 8 70 % at 15 years (worse in younger patients, mitral position). \200 Freedom from reoperation (for pa nnus, endocarditis, thrombosis) for mechanical valves > 95 % at 10 years and approximately 90 % at 10 years. Risks: Earlier-generation valves, young age, mitral position, renal failure (because of the greater pressure differential across the closed mitral valve in systole, compared to the c losed aortic valve in diastole): \200 no clear evidence that porcine > bovine, stented > stentless, homografts > xenografts although renal failure predisposes to accelerated calci \201 cation, there is no increase in reoperation, because of lower life expectancy. Investigation: Clinical and TTE \201 ndings of regurgitation or stenosis. Treatment: As for primary valve lesion, although closer follow-up is required as prosthetic valve function can deteriorate more quickly: reoperation poses 1 \200\2235 % extra risk of mortality/morbidity above \201 rst-time surgery. Patient-prosthesis mismatch AVR \200\230too small \200\231 for patient: de \201 ned as: \200 effective ori \201 ce area (EOA) is less than that of a normal human valve \200 ER O indexed to body surface area (BSA) <0.85 cm 2 /m 2 (normal indexed EOA<2.0 0.3 cm 2 /m 2 ). A 21 mm Carpentier \200\223Edwards Perimount valve has an EOA of 1.2 cm 2 , and would provi de an indexed EOA of <0.8 cm 2 /m 2 if inserted into a patient with BSA > 1.6 m 2 . Severe patient-prosthesis mismatch (PPM) is EOA <0.65cm 2 /m 2 . Incidence: Severe PPM 8 2 \200\22311 % of postoperative AVR. Stented valves in smaller sizes are partially stenotic, and mild to moderate transvalvular aortic gradients are not uncommon in the immediate posto perative period. The data regarding the clinical relevance of patient prosthesis mismatch a re con \202 icting: de \201 nitions of mismatch, baseline patient charac- teristics, and end-points vary widely between studies. Several studies link PPM with decreased postoperati ve cardiac index and New York Heart Association (NYHA) functional class, and reduced LV mas s regression, poorer survival, and late adverse events. 186 CHAPTER 3 Valvular heart disease Paravalvular leak Incidence: 0 \200\2231.5 % per patient-year. Risk: St Jude Silzone val ves, thinner sewing rings, calci \201 ed annulus, incomplete debridement of calcium/previo us sutures, active endocarditis. Late paravalvular leaks are suggestive of prosthetic valve endocarditis. Paravalvular leaks generally result in haemolysis that is more severe than that associated with older, normal ly functioning, prosthetic valves. Investigation: TTE, endocarditis work-up, screen for haemolysis. Treatment: Severe haemolysis, insuf \201 ciency, valve dehiscence, evidence of endocarditi s are surgical indications, otherwise frequent TTE follow-up. 187 Chapter 4 Infective endocarditis Presentation of endocarditis 188 Diagnosis of endocarditis 190 Investigation of endocarditi s 192 Antibiotics in endocarditis 194 Stopping endocarditis treatment 196 Culture-negative endocarditis 198 Prosthetic valve endocarditis 200 Surgery for endocarditis 202 Endocarditi s prophylaxis 206 Outpatient review 208 188 CHAPTER 4 Infective endocarditis Presentation of endocarditis Key facts \200 Highly variable presentation \200\224 depend s on intracardiac pathology, virulence of organism, and extracardiac involvement. Presentation can be insidious, as in streptococcal infections, or with striking constitutional symptoms as in Staphylococcus aureus infection. Presenting features can include those discussed next. General manifestations of sepsis Includes malaise, anorexia, weight loss, fever, rigors, an d night sweats. Longstanding infection produces anemia, clubbing, and splenomegaly. Cardiac manifestations of endocarditis \200 Sepsis causing tachycardia, hypotension. \200 Valve destruction results in a new or changing murmur. This may result in progressive heart failure and pulmonary oedema. A new harsh pansystolic murmur and acute deterioration may be due to perforation of the int erventricular septum or rupture of a sinus of Valsalva aneurysm into the right ventricle. High-degree atrioventricular (AV) block (2 \200\2234 % of infective endocarditis (IE)) occurs with intracardiac extension of infection into the interventricular septum (e.g . from aortic valve). Intracardiac abscess may be seen with any valve infection (25 \200\22350 % of aortic endoca rditis, 1 \200\2235 % of mitral but rarely with tricuspid) and is most common in prosthetic valve endocarditis. Pericarditis. Manifestations of immune complex deposition Skin : Petechiae (most common), splinter hemorr hages; Osler \200\231s nodes (small tender nodules (pulp infarcts) on hands and feet and pe rsist hours to days); Janeway lesions (non-tender eryhthematous and/or haemorrhagic areas o n the palms and soles). Eye : Roth spots (oval retinal hemorrhages with a pale center locat ed near the optic disc), conjunctival splinter hemorrhages, retinal \202 ame hemorrhages. Renal : Microscopic haematuria, glomerulonephritis and renal impairment. Cerebral : Toxic encephalopathy. Musculoskeletal : Arthralgia or arthritis. Systemic manifestations of endocarditis General manifestations of sepsis Includes malaise, anorexia, weight loss, fever, rigors, and night sweats. Longstanding infection produces ane mia, clubbing, and splenomegaly. Septic emboli \200 Septic emboli are seen in 20 \200\22345 % of patients and may involve any circulation (brain, limbs, coronary, kidney, or spleen; pulmonary emboli with tricuspid end ocarditis (see b Right-sided endocarditis, p. 190). \200 40 % of patients who have had a n embolic event will have another. \200 The risk depends on the organism (most common wit h Gram-negative infections, S. aureus or candida) and the presence and size of vegetations PRESENTATION OF ENDOCARDITIS 189 (emboli in 30 % of patients with no vegetation on echocardio graphy, 40 % with vegetations <5 mm and 65 % with vegetations > 5 mm). Ask speci \201 cally for a history of dental work, infections, surgery, intravenous (IV) d rug use, or instrumentation, which may have led to a bacteraemia. \200 Examine for any po tential sources of infection, e.g. teeth/skin lesions. \200 Risk factors for endocarditis are shown in the box below. Risk factors for infective endocarditis High risk Prosthetic valves Previous bacterial endocarditis Aortic valve disease Mitral regurgitation or mixed mitral disease Cyanotic congenital heart disease Patent ductus arteriosis Uncorrected LlR shunt Intracardiac and systemic-pulmonary shunts Moderate risk Mitral valve prolapse (MVP) with regurgitation or valve thickening Isolated mitral stenosis Tricuspid valve disease Pulmonary stenosis Hypertrophic cardiomyopathy Bicuspid aortic valve disease Degenerative valve disease in elderly Mural thrombus (e.g. post infarction) Low risk MVP without regurgitation Tricuspid incompetence without structural abnormality Isolated atrial septal defect (ASD) Surgically corrected LlR shunt with no residual shunt C alci \201 cation of mitral valve (MV) annulus Ischaemic heart disease and/or previous coronary artery bypass graft (CABG) Permanent pacemaker Atrial myxoma Other predisposing factors \200 Arterial prostheses or arteriovenous \201 stulae \200 Recurrent bacteraemia, e.g. IV drug users, severe periodontal disease, colon carcinoma) Conditions predisposing to infections, e.g. diabetes, renal failure, alcoholism, immunosuppression) \200 Recent central line. In many cases no obvious risk factor is identi \201 ed. 190 CHAPTER 4 Infective endocarditis Diagnosis of endocarditis Key facts \200 Clinical features can be non-speci \201 c and d iagnosis dif \201 cult. \200 Maintain a high index of suspicion in patients presenting w ith unexplained fever, a predisposing cardiac lesion, bacteraemia, and embolic phenomena. Duke classi \201 cation \200 Developed in 1994 as a means of standardizing the diagnosis of IE \200 Highly speci \201 c (99 % ) and sensitive (92 % ) \200 Several modi \201 cations, the most current version is described next. Major criteria \200 Positive blood culture Typical microorganism for IE from two separate blood cultures 1 \200 Persistently positiv e blood culture 2 \200 Single positive blood culture for Coxiella Burnettii or phase I \200 antibody \200 Titre to C. Burnettii > 1:800 Evidence of endocardial involvement : positive echocardiogram oscillating intracardiac mass (vegetation) \200 abscess \200 new partial dehiscence of prosthetic valve \200 new valve regurgitation. Minor criteria \200 Predisposing condition or drug use \200 Fever > 38 o C \200 Vascu lar phenomena : arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial and conjunctival hemorrhage, Janeway lesions \200 Immunologic phenomena : glomerulonephri tis, Osler \200\231s nodes, Roth spots, rheumatoid factor Microbiological evidence : positive blood cultures but not meeting major criteria or serological evidence of organism consistent with IE \200 Echocardiogram : pos itive for IE but not meeting major criteria \200 Always consider this diagnosis in IV dru g users (or patients with \200 venous access). \200 Endocarditis on endocardial permane nt pacemaker leads is a rare but recognized cause. Right-sided endocarditis \200 Patients most commonly have staphylococcal infection and ar e unwell, requiring immediate treatment and often early surgery. Lesions may be sterilized with IV antibiotics. 1 Strep viridans, strep bovis, HACEK group (HACEK = Haemophilus , Actinobacillus , Cardioba cterium , Eikenella , and Kingella spp.), community-acquired Staphylococcus aureus , or ent erococci in the absence of primary focus. 2 Blood cultures drawn 12 hours apart or 3 or mor e cultures with the \201 rst and last drawn 1 hour apart. DIAGNOSIS OF ENDOCARDITIS 191 Surgery may be required for: resistant organisms ( Staphylococcus aureus , Pseudomonas , Candida and infection with multiple organisms). increasing vegetation size in spite of therapy. \200 infections on pacemaker leads (surgi cal removal of lead and repair or excision of tricuspid valve). recurrent mycotic emboli. Criteria for de \201 nite diagnosis \200 De \201 nite endocarditis : 2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria Possible endocarditis : \201 ndings that fall short of de \201 nite endocarditis but are not rejected Rejected diagnosis : \201 rm alternative diagnosis, or sustained resolution of clinical features with <4 days of antibiotic therapy Common organisms in IE 50 \200\22360 % Streptococci (esp. Strep. viridans group) 10 % Enterococci 25 % Staphylococci S. aureus = coagulase + ve S. epidermidis = coagulase \200\223ve 5 \200\22310 % Culture negative <1 % Gram-negative bacilli <1 % Multiple organisms <1 % Diphtheroids <1 % Fungi 192 CHAPTER 4 Infective endocarditis Investigation of endocarditis Blood cultures Take 3 \200\2234 sets of cultures from different sites at least an hour apart and inoculate a minimum of 10 mL/bottle for the optimal pick-up rate. Both aerobic and anaerobic bottles must be used. Lab should be advised that IE is a possibility, especially if unusual organi sms are suspected. In stable patients on antibiotic therapy, doses must be delayed to allow culture on successive days. Ask for prolonged (fungal) cultures in IV drug users. Full blood May show normochromic, normocytic anemia (exclude haematinic de \201 ciency), neutrophil l eucocytosis, and perhaps thrombocytopenia. count (FBC) Urea and May be deranged (this should be monitored throughout treatment). electrolytes (U&Es) Liver function tests (LFTs) May be deranged, especially with an increase in alkaline phosphatase (ALP) and gamma glutam yl transferase (GGT). Erythrocyte Acute phase reaction. sedinemtation rate (ESR)/C-reactive protein (CRP) Urinalysis \200 Immunology Microscopic haematuria proteinuria. Polyclonal elevation in serum Igs, complement levels Electrocardiogram May have changes associated with any underlying cause. There may be atrioventricular (AV) b lock or conduction defects (especially aortic root abscess) and, rarely (embolic), acute my ocardial infarction (MI). (ECG) Chest X-ray May be normal. Look for pulmonary oedema or multiple infected or infarcted areas from septi c emboli (tricuspid endocarditis). (CXR) INVESTIGATION OF ENDOCARDITIS 193 Echocardiography Transthoracic ECHO may con \201 rm the presence of valve lesions and/or demonstrate vegeta tions if > 2 mm in size. Transoesophageal echocardiography (TOE) is more sensitive for aort ic root abcess and mitral lea \202 et involvement. A normal ECHO does not exclude the diag nosis. (ECHO) Magnetic Useful in investigation of paravalvular extension, aortic root aneurysm, and \201 stulas. resonance imaging (MRI, used rarely) Dentition All patients should have an OPG (orthopentamogram \200\224 a panoramic dental X-ray) and a dental opinion. Swabs \200 Ventilation/ perfusion (V/Q) scan \200 Save serum for: Any potential sites of infection (skin lesions). In cases where right-sided endocarditis is suspected, this may show multiple mismatched def ects. Aspergillus precipitins; Candida antibodies (rise in titre); Q fever ( Coxiella burnetti ) complement \201 xation test; Chlamydia complement \201 xation test; Brucella agglutinin s; Legionella antibodies; Bartonella species . Further reading Guidelines on the Prevention, Diagnosis, and Treatment of Infective Endocar ditis (new version 2009), The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 30 : 2369 \200\223 413 . Y http: //www.escardio. org/guidelines-surveys/esc-guidelines/Pages/infective-endocarditis.aspx 194 CHAPTER 4 Infective endocarditis Antibiotics in endocarditis Key facts \200 Be guided by your local microbiologist and alw ays follow local antibiotic prescription guidelines. Once diagnosis is con \201 rmed (or even suspected), explain to the patient the need for a prolonged parenteral (usually IV) course of antibiotics. \200 Microbiology will determin e sensitivities to, and minimum inhibitory concentration (MIC) of, appropriate antibiotics \200\224 if fully sensitive organism with \200\230low \200\231 MIC then shorter courses o f antibiotics may suf \201 ce (and the latter part of the course may be completed on an ou tpatient basis). Evidence shows that combination therapy is more effective than single chem otherapeutic agents. Identi \201 cation of an organism is invaluable for further management, and blood cultures should be taken before antibiotics, with meticulous attention to detail. Speci \201 c antibiotic therapy Streptococcus viridans group \200 Fully sensitive (MIC o f penicillin <0.1 mg/L) \200\224 native valve endocarditis (NVE): benzylpenicillin 1.2 g/4 h IV for 4 weeks, occasionally can successfully treat with 2-week course of benzylpenicillin and gentamicin. For prosthetic va lve endocarditis (PVE): benzylpenicillin for 6 weeks (in combination with gentamicin for \201 rst 2 weeks). Mild penicillin resistance (MIC of penicillin > 0.1 \200\2230.5 mg/L) \200\224 NVE: benzyl penicillin for 4 weeks with gentamicin for \201 rst 2 weeks. PVE: benzylpenicillin for 6 weeks with gentamicin for \201 rst 4 weeks. \200 Moderate penicillin resistance (MIC > 0.5 mg/L) \200\224 NVE: benzylpenicillin (or amoxicillin) and gentamicin for 4 \200\2236 w eeks. PVE: benzylpenicillin (or amoxicillin) and gentamicin for at least 6 weeks. \200 NB : can use vancomycin if allergic to penicillin. Staphylococcus species \200 Meticillin-se nsitive staphylococci \200\224 NVE: \202 ucloxacillin 2 g/6 hours IV for 4 \200\2236 wee ks with gentamicin for at least 1st week. PVE: \202 ucloxacillin for 6 weeks + gentamicin for \201 rst 2 weeks + rifampicin 600 mg bd PO for 6 weeks. Meticillin-resistant staphylococci \200\224 NVE: IV vancomycin for 4 \200\2236 weeks 9 gen tamicin for 1st week. PVE: vancomycin + rifampicin for 6 weeks + gentamicin for 2 weeks. Enterococcus species \200 As for streptococcus with moderate penicillin resistance (above ). HACEK species \200 NVE: IV cephalosporin (e.g. ceftriaxone) for 4 weeks, or 6 weeks fo r PVE. ANTIBIOTICS IN ENDOCARDITIS 195 Coxiella burnetii (Q fever) \200 NVE and PVE: requires prolonged (3 \200\2234 years) ther apy with tetracycline (e.g. doxycycline) and second agent (co-trimoxazole, rifampicin, quinolone) with careful mo nitoring of immunoglobulin G (IgG) titres. Usually requires surgery. Empirical therapy \200 Infective endocarditis is usually a clinical diagnosis and must be considered in any patient with a typical history, fever, and a murmur with no other explana tion. Often antibiotics need to be started before the culture results are available. Be gui ded by the clinical setting (see Table 4 .1 1 ). Table 4.1 Presentation of endocarditis Presentation Choice of antibiotic Gradual onset (weeks) Benzylpenicillin + gentamicin Acute onset (days) or history of skin trauma Flucloxacillin + gentamicin Vancomycin (or teicoplanin) + gentamicin + rifampicin Recent valve prosthesis (possible meticillin-resistant S. aureus (MRSA), diphtheroid, Klebs iella , corynebacterium, or nosocomial staphylococci) IV drug user Vancomycin Suggested antibiotic doses Benzylpenicillin Flucloxacillin Vancomycin Gentamicin Rifampicin Cipro \202 oxacin 4 MU (2.4 g) q4h IV 2 g qds IV 15 mg/kg q12h IV over 60 min, guided by levels 3 mg/kg divid ed in 1 \200\2233 doses guided by levels 300 mg q12h po 400mg q12h IV for 1 week, then 750 mg q12h PO for 3 weeks IV antibiotics should be given via a tunneled CVP (central venous pressure (Hickman)) line. Antibiotic therapy may be modi \201 ed for sensitivities. \200 Suggested antibiotic comb inations are shown above; however, individual units may have speci \201 c policies; individual patients should be discussed w ith your local microbiologist. 1 Oakley CM (1995). The medical treatment of culture-negative infective endocarditis. Eur H eart J 16(suppl B): 90 \200\2233. 196 CHAPTER 4 Infective endocarditis Stopping endocarditis treatment Duration of treatment \200 Controversial \200\224 a tren d toward shorter courses. Microbiology and ID opinion is important, especially in resistant and/or uncommon organisms. The box below shows one suggested protocol. The duration of treatment varies depending on the severity of infection and the infecting o rganism. IV therapy is usually for at least 2 weeks, and total antibiotic therapy for 4 \200\2236 weeks. If the patient is well following this period, antibiotic treatment may be stopped. Provided no surgery is indicated (see b Surgery for endocarditis, p. 202), the patient may be disch arged and followed up in outpatient clinic. Patients should be advised of the need for endocarditis prophylaxis in the future (see b Endocarditis prophylaxis. p. 206). Patients with valvular damage following infection should be followed long term, and patient s with ventricular septal defects should be considered for closure. Viridans streptococci and Streptococcus bovis (penicillin sensitive) Benzylpenicillin only (4 weeks) Vancomycin or teicoplanin (4 weeks) Penicillin + aminoglyco side (2 weeks) Ceftriaxone 2 g (4 weeks) Group B, C, G streptococci, Strep. pyogenes , Strep. pneumoniae Penicillin (4 weeks) + aminoglycoside (2 weeks) Vancomycin (4 weeks) + aminoglycoside (2 we eks) Group A streptococci Penicillin (4 weeks) Vancomycin (4 weeks) Enterococci Penicillin + aminoglycoside (4 \200\2236 weeks) Vancomycin + aminoglycoside (4 \200\2236wee ks) \200 Extracardiac infection from septic emboli Penicillin (4 weeks) + aminoglycoside (2 weeks) Vancomycin (4 weeks) + aminoglycoside (2 we eks) Staphylococcus aureus and coagulase-negative staphylococci Left-sided endocarditis: Flucloxacillin (4 \200\2236 weeks) + aminoglycoside (2 weeks) If MRSA \200\224 vancomycin + rifampicin (6 weeks) aminoglycoside (2 weeks) Right-sided endocarditis: Flucloxacillin (2 weeks) + aminoglycoside (2 weeks) Cipro \202 oxacin (4 weeks) + rifampic in (3 weeks) If MRSA \200\224 vancomycin (4 weeks) + rifampicin (4 weeks) Fungi Amphotericin B IV to a total dose of 2.5 \200\2233 g STOPPING ENDOCARDITIS TREATMENT 197 Monitoring treatment Patients need careful clinical monitoring both during and for several months after the infection. Reappearance of features suggestive of IE must be investigated thoroughly to rule out recurrent infection or resistance to the treatment regime. Clinical features of progressive endocarditis \200 Signs of continued infection, persiste nt pyrexia, and the persistence of systemic symptoms Persistent fever may be due to drug resistance, concomitant infection (central line, urine, chest, septic emboli to lungs or abdomen), or allergy (?eosinophilia, ?leucopenia, ?proteinuria: common with penicillin but may be due to any antibiotic \200\224 consider changing or stopping antibiotics for 2 \200\2233 days) \200 Changes in any cardiac murmurs or signs of cardiac failure \200 The development of any new embolic phenomena \200 Inspect venous access s ites daily. Change peripheral cannulae every 3 \200\2234 days. Echocardiography \200 Regular (weekly) transthoracic echocardiograms may identify clinica lly silent, but progressive, valve destruction and development of intracardiac abscesses or veg etations. The tips of longstanding central lines may develop sterile \201 brinous \200\230fronds \200\231, which may be visible on TOE: change the line and send the tip for culture. \200\230Vegetations \200\231 need not be due to infection (see b Causes of \200\230vegetations \200\231 on ECHO, Culture-negative endocarditis, p. 199). ECG \200 Look speci \201 cally for AV block or conduction abnormalities suggesting intracardiac extension of the infection. A daily ECG must be performed. Microbiology \200 Repeated blood cultures (especially if there is continued fever) \200 Regular aminoglycoside and vancomycin levels (ensuring the absence of toxic levels and the presence of therapeutic levels). Gentamicin ototoxicity may develop wi th prolonged use even in the absence of toxic levels Back titration to ensure that minimum inhibitory and bactericidal concentrations are being achieved. Laboratory indices \200 Regular (daily) urinalysis \200 Regular U&Es and LFTs \200 Re gular CRP (ESR every 2 weeks) \200 FBC \200\224 rising hemoglobin (Hb) and falling white cell count (WCC) suggests successful treatment; watch for beta-lactam-associated neutropen ia Serum magnesium (if on gentamicin). 198 CHAPTER 4 Infective endocarditis Culture-negative endocarditis \200 The commonest reason for persistently negative blood c ultures is prior antibiotic therapy and affects up to 15 % of patients with diagnosis of IE . If the clinical response to the antibiotics is good, these should be continued. For a persisting fever: withhold antibiotics if not already started \200 consider other investigations for a \200\230PUO \200\231 (pyrexia of unknown origin) if there the clinical suspicion of IE is high, it warrants further investigation repeated physical examination for any new signs \200 regular ECHO and TOE. \200\230Veget ations \200\231 need not be due to infection (see b p.199) repeated blood cultures, especially when the temperature is raised. Discuss with microbiology about prolonged culturing times (4 + weeks) and special c ulturing and subculturing techniques. Most HACEK group organisms can be detected Consider unusual causes of endocarditis: Q-fever (Coxiella burnetii) : complement \201 xation tests identify