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Clinical Spotlight
A Case of Intra-Cardiac Right-Sided Mural Infective Endocarditis Associated with Ventricular Septal Defect Despite Prophylactic Antibiotics: A Case Report Tina Lin, MBBS a,∗ , Maria Santos, MD a,1 , Craig Aboltins, FRACP b , Herman Chiu, FACEM c , William Van Gaal, FRACP MD a,1 and Chiew Wong, FRACP a,1 a Department of Cardiology, Northern Health, 185 Cooper Street, Epping, Victoria 3076, Australia Department of Infectious Diseases, Northern Health, 185 Cooper Street, Epping, Victoria 3076, Australia Department of Emergency Medicine, Northern Health, 185 Cooper Street, Epping, Victoria 3076, Australia
b c
Bacterial endocarditis secondary to jet lesions from congenital heart disease is not uncommon, and has been reported on numerous occasions in the literature. These cases usually involve one or more cardiac valves. Our case is that of isolated intracardiac right-sided mural infective endocarditis associated with ventricular septal defect. Importantly, this patient had preceding dental work treated with antibiotic prophylaxis. This case highlights bacteraemia secondary to dental instrumentation versus routine oral hygiene. His presentation was predominantly that of respiratory symptoms and sepsis, and he was culture negative throughout his admission. The lesion was detailed on echocardiography and transoesophageal echocardiography, and treated conservatively. He has subsequently been referred for VSD closure. (Heart, Lung and Circulation 2010;19:566–571) Crown Copyright © 2010 Published by Elsevier Inc. on behalf of Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. All rights reserved. Keywords. Endocarditis; Intracardiac right mural; Ventricular septal defect; Antibiotic prophylaxis guidelines
Introduction
I
nfective endocarditis associated with congenital heart disease continues to be an important issue, raising ongoing debate with regard to when antibiotic prophylaxis is appropriate. Endocarditis secondary to jet lesions has been regularly described in the literature. In recent reviews, the incidence of bacterial endocarditis is reported to be up to 9% of patients across all subtypes, including ventricular septal defects (VSD), and post-dental instrumentation was the leading cause (33% of cases) [1]. The most frequent complication from variations of isolated right-sided endocarditis is recurrent pulmonary emboli (29% of complications) [2]. Therefore, in patients presenting with fevers, respiratory symptoms, and predisposing structural heart disease, isolated right-sided endocarditis should be included in the Received 30 September 2009; received in revised form 22 April 2010; accepted 3 May 2010; available online 11 June 2010 ∗
Corresponding author. Fax: +61 8405 8405. E-mail addresses:
[email protected] (T. Lin),
[email protected] (M. Santos),
[email protected] (C. Aboltins),
[email protected] (H. Chiu),
[email protected] (W. Van Gaal),
[email protected] (C. Wong) 1 Fax: +61 8405 8405.
differential diagnosis, even in the absence of injecting drug use. The most current Australasian guidelines for endocarditis prophylaxis states that in patients with unrepaired, non-cyanotic congenital heart disease, including VSD as in our patient, antibiotic prophylaxis is not indicated in the absence of previous infective endocarditis [3]. We present an unusual case of isolated right-sided mural infective endocarditis with pulmonary involvement and without valvular involvement associated with congenital VSD. This was in the setting of recent dental instrumentation and the use of antibiotic prophylaxis.
Case Report A 21-year-old Australian born Malaysian man presented from home with a three-week history of cough productive of yellow sputum, drenching night sweats and lethargy. This was associated with loss of appetite. Notably, the patient noticed a gradual weight loss of ∼15 kg over a six month period. He initially presented to his general practitioner after one week of symptoms, and was not initially treated. He represented to his general practitioner after one week of unresolved symptoms, and was prescribed roxithromycin for presumed pneumonia. Although he had
Crown Copyright © 2010 Published by Elsevier Inc. on behalf of Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. All rights reserved.
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some improvement of his cough, his symptoms persisted, and he presented to the emergency department. On other initial history, there was no report of documented fevers, rigors or myalgia. In regards to other localising symptoms, he described no dysuria, polyuria, abdominal pain or change in bowel habit, skin lesions, headache or neck stiffness. Other than the productive cough, he had no haemoptysis and no history of a hypercoagulable state. He had no history of infective contacts, no recent travel and no history of tuberculosis. He denies any history of injecting drug use. Notably, the patient had been having regular dental instrumentation done for insertion of a dental bridge, and one week preceding the onset of symptoms, he had his last dental instrumentation preformed. He had been given amoxicillin for endocarditis prophylaxis on each occasion. His past medical history was significant for a VSD diagnosed at two years of age. This was diagnosed after he presented with persistent lethargy. He had been followed up by a cardiologist and monitored with yearly transthoracic echocardiography (TTE). The last had been performed 10 months prior. The report described a small perimembranous VSD with trivial increase in the main pulmonary artery velocities. Physical examination revealed a heart rate of 110 beats/min, blood pressure of 130/80 mm Hg. He was afebrile throughout his admission. There were no peripheral stigmata of endocarditis and there was no evidence of active sediment on urinalysis. Cardiac examination revealed a harsh ejection systolic murmur at the left sternal edge consistent with his known VSD. Jugular venous pressure was at ∼5 cm above the sternomanubrial notch. Auscultation of the lung fields found left basal crepitations. There were no other signs of cardiac failure. There were no neurological or abdominal signs to suggest embolisation.
Lin et al. A Case of Intra-Cardiac Right-Sided Mural Infective Endocarditis
Table 1. Laboratory Results (bolded values are abnormal). Presentation Hb (g/L) WCC (×109 /L) Plat (×109 /L) MCV (fL) Neut (×109 /L) CRP (mg/L) Rh F (IU/mL)
103 14.7 404 85 8.3 228.6 90 25 16 216 59 97
heart endocarditis is more likely given the chest X-ray findings and presence of respiratory symptoms and signs. This is rare with ventricular septal defects but it still has to be the focus of investigation in the emergency department. Laboratory findings showed normocytic normochromic anaemia, elevated inflammatory markers, and hypoalbuminaemia. Rheumatoid factor was negative (Table 1). Anticardiolipin antibodies and ANA were similarly negative. Blood and sputum cultures were negative throughout his hospital stay. Mycobacterial/fungal blood cultures, Coxiella, Bartonella, and atypical pneumonia serology were also negative. Chest X-ray showed patchy alveolar changes throughout the lung fields, consistent with consolidation (Fig. 1). Computer tomography of the chest confirmed multiple foci of air space opacity throughout both lung fields with cavitating areas consistent with multiple septic emboli and abscess formation. There was no lymphadenopathy (Fig. 2). An echocardiographic study was performed on admission. This revealed the previously known membranous
Expert Commentary on Initial Clinical Differential Diagnoses: Emergency Physician, Dr. Herman Chiu (MBBS, FACEM) The combination of a productive cough, night sweats and loss of weight would immediately make the Emergency Physician consider a respiratory source of infection as the most likely diagnois, including lung abscess. Atypical pneumonia, however, is less likely given the duration of symptoms of more than 10 days, and the lack of improvement after a one-week course of roxithromycin. Tuberculosis is unlikely given that the patient had no infective contacts, no overseas travel, and lived in Australia his entire life. Other respiratory infections to consider include those associated with immunosuppression such as pneumocystis and cryptococcal pneumonia. Less likely still but worth some consideration is Systemic Lupus Erythematosis and other immune mediated conditions. Females are much more likely to have SLE and there should be the presence of extrapulmonary symptoms. However the history of ventricular septal defect, recent dental procedure and the duration of illness make subacute bacterial endocarditis a very likely possibility. Right
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Figure 1. Chest X-ray showing patchy alveolar opacities.
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Lin et al. A Case of Intra-Cardiac Right-Sided Mural Infective Endocarditis
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Figure 2. CT chest showing septic emboli.
VSD with left-to-right shunt, measuring 0.7 cm on twodimensional images. There was an associated large mobile echo density in the right ventricular outflow tract (RVOT) and VSD. This was further evaluated with transoesophageal echocardiography (TOE), which confirms a large vegetation measuring 4.1 cm × 1.6 cm, attached to the right ventricular free wall near the RVOT (Fig. 3). A separate lesion was seen attached to the right ventricular side of the septal defect (Fig. 4). There was no valvular involvement, in particular the tricuspid or the pulmonary valves.
Expert Commentary from Echocardiologist: Co-Director of Echocardiography, Dr. Chiew Wong (MBBS, FRACP) There was right-sided ventricular free wall vegetations characterised by jet lesions arising from high velocity jets, from a ventricular septal defect in this case (Fig. 3). The vegetations would have involved the septal defect first as shown in the transoesophageal echocardiogram with residual deposits seen at the exit of the turbulent jet (Fig. 4a). The bulk of the vegetation, however, was attached to the right ventricular free wall (Fig. 3). Using transoesophageal echocardiography, we were able to directly visualise the path of the jet and full extent of the endo-
carditis. We examined carefully the tricuspid valve due to the proximity of the vegetation. Fortunately, the tricuspid valve apparatus was spared. Our case illustrates the importance the jet lesion may have in the pathophysiology of bacterial endocarditis. The sites of the involvement are quite classical as it is typically located distal to an orifice between a high-pressure jet and a low-pressure sink. A high-pressure jet can cause direct endothelial damage at its point of impact which may serve as a nidus for bacterial infection. The final TOE images obtained five months post presentation revealed no evidence of vegetations, with no valvular pathology. The patient has been referred for consideration of VSD closure.
Expert Commentary from Infectious Diseases Physician: Dr. Craig Aboltins (MBBS, FRACP (Hons)) Cultures in infective endocarditis remain negative in approximately 6% of patients. This frequency is even higher in patients who have been given antibiotics prior to blood cultures being obtained, such as with this patient. The management of culture negative endocarditis is controversial but in general consideration needs to be given
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Figure 4. TOE images of (a) a large vegetation attached to the right ventricular side of the VSD and (b) right-sided mural wall lesions in the direction of the VSD shunt jet.
Given the remarkably large size of the vegetation and the presence of septic emboli the question of surgical removal of the vegetation to prevent further embolism was raised. A decision to proceed with medical therapy alone was made, however, as the patient had already commenced on antimicrobial therapy at the time, reducing the risk of further embolism and also as the lesion was right sided, meaning risk of serious consequences was lower.
Discussion Figure 3. TOE image of (a) a bulky mass of vegetation measuring 4.1 cm × 1.6 cm, (b) vegetation opposite the jet direction of the left to right shunt across the VSD, (c) Doppler jet directed at the vegetation.
to treating for Streptococci, Enterococci, HACEK organisms, Bartonella, Coxiella burnetii, Legionella and Mycoplasma species [4]. In this case, negative cultures after oral roxithromycin and negative serology for Bartonella, C. burnetii, Legionella and Mycoplasma, led to an antibiotic regimen mainly directed towards either a sensitive streptococcus or HACEK organism, with benzylpenicillin and ceftriaxone (and doxycycline until serology results were available), for six weeks.
Although the incidence of infective endocarditis is very low in the general population, the high morbidity and mortality this illness can cause has lead to extensive discussion of optimising prevention. The importance of balancing the effect of infective endocarditis versus the possible adverse drug reactions has lead to expert groups around the world developing guidelines to try and assist in determining when it is appropriate to treat with prophylactic antibiotics. Previously, it had been routine practice to give prophylaxis prior to dental and many other procedures in patients with structural cardiac disease deemed at high lifetime risk of developing infective endocarditis. Although there have been animal trials that have cor-
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related bacteraemia with the development of infective endocarditis, so far there have not been any human randomised controlled trials that looks at the role of antibiotic prophylaxis in different at risk groups. The latest update in the Australian Therapeutic Guidelines (2008) [5] follows closely the American Heart Association guidelines, which trends towards reducing the groups of patients in whom prophylaxis is recommended. The major difference is that the Australian guidelines retains the group of patients of Indigenous background with rheumatic heart disease. The rationale for this trend is the evidence suggesting that overall, the risk after an individual dental or other procedure is actually quite low, and therefore antibiotic prophylaxis does not prevent many cases. The indicators of risk during bacteraemia are incidence, magnitude and duration. The indicators of risk of the procedure are state of periodontal health, amount of dentogingival manipulation and amount of bleeding, and duration. Although approximately 70% of dental procedures have high incidence of bacteraemia, daily oral hygiene activities (toothbrushing, flossing, oral irrigators) also produce incidences of bacteraemia. As the frequency of these activities is much higher, the cumulative effect leads to longer periods of bacteraemia and therefore increased risk of infective endocarditis [6]. Prior to the publication of the latest therapeutic guidelines for endocarditis prophylaxis, patients with congenital heart disease or certain acquired cardiac diseases were felt to be at increased risk of developing infective endocarditis, and were therefore recommended antibiotic prophylaxis. This is due to the pathogenesis of the development of endocarditis. The jet flow caused by the structural abnormality continuously traumatises a section of endothelium, which makes it more susceptible to bacterial colonisation during bacteraemia. With the new recommendations, many of the previously included structural heart diseases, including unrepaired ventricular septal defects, are now no longer in the high-risk group. However, due to the cumulative periods of bacteraemia during day-to-day oral hygiene activities, the need to optimise good dental hygiene to reduce amount of bacteraemia is highlighted. In our case, the use of antibiotic prophylaxis was given as per previous guidelines, which is still the practice in many cases, especially in patients who have been receiving prophylaxis throughout their lifetime. The need for future prophylaxis for this patient also becomes important, as his history of infective endoarditis puts his cardiac condition definitely into the highest risk group. For our patient, endocarditis developed in the setting of frequent dental procedures where antibiotic prophylaxis was given. The role of this dental instrumentation in causing the endocarditis is unclear, especially given the pathogenic organism was not isolated. Given blood cultures were probably rendered negative by the preceding course of roxithromycin, the organism is likely to have been a sensitive one, such as a viridans streptococcus, meaning that the prophylactic amoxicillin should have been effective. Therefore the procedures may have been coincidental but it needs to be considered that they may
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have led to the infection through an increased risk of cumulative bacteraemia in combination with his subsequent daily oral hygiene routine. The incidence of endocarditis in patients with VSD has been shown to be very low. However, in the select population with clinical or echocardiographic signs of VSD, consideration of isolated right-sided infective endocarditis should be given in patients who present with systemic symptoms of fevers. While this more commonly involves the tricuspid and/or the pulmonary valves, there have been rare reports of right mural involvement in the literature [7,8]. The jet from a membranous VSD with leftto-right shunt is generally directed toward the base of the right ventricular free wall. Due to the vicinity of the tricuspid and pulmonary valve leaflets, the jet usually causes endothelial damage to the leaflets, creating a nidus for bacterial attachment. Once our patient had been cleared of his endocarditis, he was referred for closure of this VSD as per the guidelines for management of congenital heart disease (2008), due to the serious nature of his endocarditis and the increased risk of recurrent endocarditis [9]. By removing the high flow jet directed at the endothelium, surgical closure reduces the risk of endocarditis by more than twofold, independent of the size of the defect [10,11], with the exception of the immediate postoperative period [12]. During this six month period, the closure device is in the process of becoming endothelialised, and the presence of foreign material places these patients in the highest risk group for infective endocarditis, and are therefore recommended for antibiotic prophylaxis. In fact, there have been very few reports of closure device endocarditis in the literature after this high risk period. The additional benefit is the avoidance of long-term pulmonary vascular disease.
Conclusion Our case presents the unusual isolated involvement of the right ventricular free wall in a patient with unclosed VSD who developed infective endocarditis. It highlights the varying morphology of disease involvement, as well as the importance of considering endocarditis when these patients present with systemic symptoms. The case also points out that although the antibiotic guidelines for endocarditis prophylaxis is an important tool to guide us in our decisions for appropriate use of antibiotics in certain cardiac conditions, it may also be appropriate to individualise treatment. The importance of daily dental hygiene causing bacteraemia versus, or in addition to dental instrumentation is also highlighted in this case. In regards to the long-term follow-up and management of our patient, the guideline recommendations are for antibiotic prophylaxis with all high-risk dental, respiratory and genitourinary procedures for the duration of his lifetime. This is even after closure of his VSD and endotheliasation of the device, as he has had endocarditis in his history. It would be imperative to ensure that the patient understands the importance of antibiotic prophylaxis, and good dental hygiene to reduce his risk for further infections.
Lin et al. A Case of Intra-Cardiac Right-Sided Mural Infective Endocarditis
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