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© 2004 European Association of Cardio-Thoracic Surgery
Aspergillus aortitis: a cause for aortic perforation in a patient following combined aortic valve surgery and liver transplantation
a Department of Cardiothoracic Surgery, King's College Hospital, Denmark Hill, London SE5 9RS, UK
* Corresponding author. Tel.: +44-20-7346-3191; fax: +44-20-7346-3433 Received March 23, 2004; received in revised form May 12, 2004; accepted May 13, 2004
We report a case of aspergillus fumigatus aortitis in a patient following combined aortic valve replacement and orthotopic liver transplantation for significant aortic stenosis and alcoholic liver cirrhosis. At operation, a suspicious excavating lesion was found on the native aortic valve and specimen sent for culture. The ascending aorta and aortic sinuses were found to be normal. Routine immunosuppression was commenced post transplant. Urgent valve microscopy was highly suspicious of fungal growth, and antifungal therapy was instituted. Day 18 post-surgery the patient unexpectedly arrested. Post mortem findings showed ascending aortic perforation with multiple fungal lesions noted. Microscopy demonstrated aspergillus fumigatus invading the aortic wall. This is the first case report illustrating a dormant phase of aspergillus fumigatus endocarditis that was activated following surgery and immunosuppression leading to aortitis and subsequent perforation.
Key Words: Aspergillus fumigatus; Aortitis; Perforation; Aortic valve replacement; Liver transplantation
Cardiovascular invasion by aspergillus fumigatus has rarely been reported despite the fact that it is the most common fungal commensal in humans. This fungus gains access to the vascular system as a result of immunosuppression, those undergoing transplantation and with cardiopulmonary bypass [1]. In the cases reported, aspergillus invasion of the vascular system is uniformly fatal regardless of mode of treatment [2,3]. Of all known aspergillus species, fumigatus is the most aggressive. The case presented shows an unusual presentation of aspergillus fumigatus and illustrates the aggressive nature of this organism leading invariably to death of the patient.
A 60-year-old man of Turkish origin developed alcoholic liver cirrhosis. He had no significant past medical history and had consumed over 100 units of alcohol per week for many years. During assessment for liver transplantation, a routine transthoracic echocardiogram demonstrated aortic stenosis with a gradient of 80 mmHg, and coronary angiogram showed normal coronaries. Following successful abstinence from alcohol for 6 months a combined procedure involving aortic valve replacement (AVR) and orthotopic liver transplantation (OTL) was considered. The combined procedure is believed to be lower risk than the individual operations performed at different times [4]. At operation, a standard midline sternotomy was used. The ascending aorta and pulmonary artery were normal. Following full dose heparinisation at 3 mg/kg, cardiopulmonary bypass was established with cannulation of ascending aorta and right atrium. Following aortotomy, the aortic valve was found to be stenosed and pseudobicuspid (fusion of left and right coronary cusps). A suspicious lesion was found on the commisure between the left and right coronary cusps, and this was sent for urgent microscopy. A 23 mm tissue valve (Mitroflow, Carbomedics, Sorin Group, Italy) was inserted using Teflon buttressed horizontal mattress 2/0 ethibond sutures. Aortotomy was closed with 4/0 prolene in a double layer technique. Sinus rhythm occurred after release of the crossclamp. Liver transplantation then followed the closure of the sternum. Concerns of fungal endocarditis was raised following urgent microscopy, and antifungal therapy with oral fluconazole (150 mg, once daily) started. Immunosuppression for liver transplantation was achieved with tacrolismus (1 mg, intravenous, twice daily), prednisolone (20 mg, intravenous, once daily) and methylprednisolone (16 mg, intravenous, once daily). Post operatively he was transferred to ITU where he remained in a stable condition and was extubated on day 3. On day 3, he became hypotensive with diminished urine output and an echocardiogram confirmed a significant pericardial effusion causing tamponade that required drainage via xiphisternal window and pericardial drain insertion. There was immediate drainage of 800 ml of dark blood. The patient improved substantially following this procedure. On day 7 following surgery, enriched culture plates confirmed aspergillus fumigatus growth although all blood cultures performed were negative and inflammatory markers were improving. Fluconazole was switched to lysosomal amphotercin given intravenously (250 mg, once daily). Transoesophageal echocardiography was performed which showed a normal prosthetic aortic valve and aorta with no evidence of fungal invasion. There was no evidence of pericardial effusion and the pericardial drain was removed. He continued to improve clinically. By day 17, the patient was active and mobile relying only on intravenous antifungal therapy. On day 18, he developed symptoms of chest and back pain but was haemodynamically stable, the pain settled with simple analgesia. Eight hours later, he had a pulseless electrical activity cardiac arrest and a full 5 cycle cardiopulmonary resuscitation was carried out without success. Post mortem examination revealed fresh clots in the pericardium. Macroscopic examination of the inner surface of the ascending aorta demonstrated multiple fungal lesions extending over the de-airing site where the perforation had occurred. Histopathological examination using Periodic Acid Schiff staining (Fig. 1) and Grocott Methenamine Silver staining (Fig. 2) methods confirmed aspergillus fumigatus invading the aortic wall layers contributing to aortic perforation.
This report illustrates the occult, aggressive and lethal course of aspergillus fumigatus aortitis, which unusually in this case had remained dormant pre-operatively. Even with the early diagnosis of this condition and institution of therapy the patient did not survive. Unfortunately, the need for immunosuppressants post-liver transplant may have impaired the immune response further favouring aspergillus aortitis and perforation [1]. The evidence for performing combined OLT with cardiac surgery is supported by a number of studies demonstrating poor post-operative outcomes for patients with cirrhosis undergoing cardiac surgery. A retrospective study by Hayashida et al. [4] showed that the incidence of post-operative complications (i.e. infection, respiratory failure, renal failure, bleeding and gastrointestinal disorders) in cardiac patients with cirrhosis was 60% for Child A cirrhosis (serum bilirubin <2.0 mg/dl, serum albumin >3.5 g/dl, no ascites, no neurological disorder, excellent nutrition), and 100% for Child B (serum bilirubin 2.0–3.0 mg/dl, serum albumin 3.0–3.5 g/dl, controlled ascites, minimal neurological disorder, good nutrition) and C (serum bilirubin >3.0 mg/dl, serum albumin <3.0 g/dl, poorly controlled ascites, advanced coma, nutrition poor) cirrhosis. Mortality noted in this study was 0%, 50% and 100% for Child A, B and C, respectively. In the presence of facilities for OLT, it would therefore seem logical to perform combined procedure following risk stratification. Recent evidence suggests higher risk of cardiovascular complications in patients undergoing OLT in the form of greater incidence of ischaemic events, dyslipidaemia and hypertension [5]. One should keep this in mind during post-operative follow-up. Aspergillus invasion of the vascular system requires immunosuppression of some form [1]. During routine liver transplant workup this patient was found to be free of immunodeficiency states (e.g. HIV) and had no obvious environmental risk factors (such as habitation near construction site). However, liver cirrhosis alone may have lead to sufficient immunosuppression to allow aspergillus endocarditis in the first instance. This type of presentation with a fairly indolent lesion has never been reported. Following surgery even with sufficient surgical debridement and antifungal therapy, the aspergillus infection was activated and aided by immunosuppression. In light of this patient's good pre-operative clinical status, it was felt that preliminary valve microscopy was possibly a contaminent causing the delayed institution of amphotericin. Unfortunately this may have affected outcome. Only a few cases of aspergillus fumigatus vascular invasion have been published over the years. The general conclusion is that once infection is established mortality is inevitable by a number of mechanisms including endocarditis, cerebral mycotic embolism, aortic perforation or perforation of aortic graft pseudoaneurysm [3,6–8]. This condition is rare and difficult to diagnosis. As such diagnoses are made either peri-mortem or post-mortem following a raised index of suspicion. The gold standard for diagnosis is histology [1]. Blood cultures and serum immunology (Galactomannan, In House Assay, King's College Hospital, London, UK) are unreliable and often negative. In conclusion, aspergillus fumigatus aortitis is difficult to treat and has disastrous consequences. Symptoms/signs and associated risk factors (type of surgery and immunosuppression), even with a negative blood culture should raise suspicion and prompt aggressive management. Despite all efforts, the course of disease is unfavourable.
ICVTS on-line discussion Author: Dr. Roland Demaria, Arnaud de Villeneuve Hospital, Department of Cardiovascular Surgery, Montpellier Teaching Hospital, 371 Av Doyen G. Giraud, Montpellier, 34295 France Date: 16-Jul-2004 Message: I read with interest the article by Dr. Hanvesakul and his colleagues reporting a fatal case of Aspergillus aortitis. This paper gives us the opportunity to share our recent and fatal experiences of Aspergillus cardiovascular infestations. The first case we encountered was a teenager treated for acute leukemia. He developed a lung abscess and a mitral valve endocarditis with large vegetations. After antifungal therapy, the lobe containing the abscess was removed and the mitral valve was replaced. Cultures recovered an Aspergillus flavus. Despite antifungal therapy, he developed fatal embolism [1]. The second case was a 67 year old man, with diabetes and hemochromatose who presented an Aspergillus endocarditis on pacemaker leads. The surgical ablation of the material associated with antifungal treatment could not prevent the fatal evolution with a multi organ failure. The cultures recovered an Aspergillus fumigatus [2]. All thoracic and cardiovascular surgeons must be aware of this dreadful pathology. Usually, Aspergillus endocarditis (more frequent than aortitis) is caused by direct contamination during open heart surgery on an immunodepressive patient. Arterial emboli are frequent, due to very large vegetations. Blood cultures performed were often negative and diagnosis confirmation rests upon histology. Medical treatment should be started as soon as the diagnosis is suspected, as it was in the case here. Intravenous amphotericin B is the agent most often used for Aspergillus. Once antifungal therapy has been initiated, the infected tissue should be replaced as soon as possible. Despite this optimal treatment, the mortality rate remains higher than 50% [3]. References [1] Demaria RG, Dürrleman N, Rispail P, Margueritte G, Macia JC, Aymard T, Frapier JM, Albat B, Chaptal PA. Aspergillus flavus mitral valve endocarditis after lung abscess. J Heart Valve Dis 2000;9:786–90. [2] Demaria R, Dürrleman N, Rouvière, Rispail P, Raczka F, Piot C, Frapier JM, Albat B. Endocardite à Aspergillus fumigatus sur sondes de stimulateur cardiaque. J Chir Thorac Cardio-Vasc 2004, in press. [3] Demaria RG, Fortier S, Perrault LP. In response to Cotrufo M, Carozza A, Romano G, De Feo M, Della Corte A. Infective endocarditis of native cardiac valves: 22 years' surgical experience. J Heart Valve Dis 2002;11:454–5. doi:10.1016/j.icvts.2004.05.009
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Abstract
1. Introduction
