Izabella Rodrigues de AraújoI; Maria do Carmo Pereira NunesI,II; Claudio Leo GelapeI; Vinicius Tostes CarvalhoI; Benone Evaristo Rezende Araújo LacerdaI; Gustavo Brandão de OliveiraI; Luiza Caldeira BrantI; Teresa Cristina Abreu FerrariI
IHospital das Clínicas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG IICurso de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG
We describe the case of a 41-year-old man with congenital heart disease and infective endocarditis (IE), who presented multiple vegetations attached to the pulmonary, mitral, and aortic valves. Three valve replacements were performed, but the patient developed an abscess at the mitral-aortic intervalvular fibrosa and died due to sepsis. We briefly discuss the indications for surgery in IE, emphasizing its role in the treatment of uncontrolled infection.
Keywords: Infection. Endocarditis. Surgery. Valves.
Paciente do sexo masculino, 41 anos, portador de cardiopatia congênita apresentando-se com endocardite infecciosa (EI) e vegetações nas valvas pulmonar, aórtica e mitral. Três trocas valvares foram realizadas, mas o paciente evoluiu com recidiva da infecção, desenvolvendo abscesso na região da fibrosa intervalvar mitro-aórtica progredindo para sépsis e óbito. Nesse relato, discutimos brevemente as indicações para a cirurgia na EI, destacando sua indicação no tratamento da infecção não controlada.
Palavras-chaves: Infecção. Endocardite. Cirurgia. Valvas.
Infective endocarditis (IE) remains a medical challenge. Despite major advances in both diagnostic and therapeutic procedures, this disease still carries a poor prognosis and a high mortality rate.
IE is not a uniform disease but presents a variety of forms, varying according to the initial clinical manifestation, the underlying cardiac disease, the microorganism involved, and the presence of complications. Thus, clinical decision-making is difficult, especially in unusual cases where there is no uniform consensus.
Herein, we report the case of a middle-aged man with a ventricular septal defect and IE with multiple vegetations attached to three different cardiac valves. The right and left heart involvement determined a peculiar evolution that posed a challenge to management.
A 41-year-old man was admitted to the University Hospital, Federal University of Minas Gerais, Belo Horizonte, Brazil, with productive cough, fever, and pain upon breathing of a few weeks’ duration. The chest X-ray showed a nodular image in the right lung and right pleural effusion. Due to suspicion of pneumonia, moxifloxacin was started. The patient was previously diagnosed with type-2 diabetes and a congenital ventricular septal defect.
Laboratory investigations showed hemoglobin level of 9g/dL, a white blood cell count of 9,880/µL, and C-reactive protein of 128mg/L (normal value < 5mg/L). Serum chemistry and urine analysis were normal. Blood cultures disclosed Enterococcus faecalis in three samples. The electrocardiogram (ECG) was unremarkable. Transthoracic echocardiography (TTE) demonstrated severe pulmonary regurgitation, a ventricular septal communication (Figure 1), and two vegetations: The larger one (23×11mm) was attached to the pulmonary leaflet and the other (7×7mm) to the aortic leaflet (Figure 2). Considering the diagnosis of IE, the initial pulmonary picture was ascribed to septic pulmonary embolism with infarction, and the antibiotic was changed to ampicilin plus gentamicin. One week later, transesophageal echocardiography (TEE) confirmed the TTE findings and additionally demonstrated a small vegetation (3×2mm) attached to the anterior mitral leaflet.
On the following 10 days of therapy, the patient remained relatively stable; however, fever persisted and the respiratory rate increased. Laboratory exams showed elevated C-reactive protein and a slight increase in the white blood cell count. New blood cultures were negative, and a new TEE revealed no further complications. Leucocytosis and the persistency of fever were attributed to infected pulmonary infarction, and meropenem was added to the antibiotic regimen. The abdominal ultrasound was unremarkable.
After a transient improvement, fever and tachypnea reappeared. Once again, the blood cultures were negative, and a new TEE showed no further evidence of IE complications. The unfavorable clinical evolution despite two weeks under specific antibiotic therapy was ascribed to locally uncontrolled infection, and for this reason, surgical treatment was indicated.
The surgical approach comprised aortic and pulmonary valve replacement, and ventricular septal communication repair. The patient remained stable, and the antibiotics were discontinued after six weeks. Approximately eight weeks after the surgery, fever and dyspnea reappeared. TEE revealed severe mitral regurgitation and a vegetation attached to the anterior mitral leaflet, which could be related to the primary aortic IE with aortic regurgitation. Antibiotics were restarted, and a new surgery was performed in order to replace the mitral valve.
The patient remained unstable, presenting hypotension and renal failure for approximately four weeks after this second surgical procedure. TEE performed at that time showed an echolucent area, suggestive of an abscess cavity at the mitral-aortic intervalvular fibrosa (Figures 3A and B). Unfortunately, the patient died due to septic shock in spite of clinicaltreatmentbeforea newsurgical interventioncould be performed.
Infective endocarditis is clearly an evolving disease with significant changes in its epidemiological profile, surgical rates, and outcome over the last few years. Congenital heart disease is the substrate for IE in 2% to 18% of the reported cases in young adults and in 8% in older individuals1-2. The risk of endocarditis seems to be related to the specific type of congenital heart lesion, being higher in cases of aortic stenosis and ventricular septal defects3.
The case reported here is very complex due to the involvement of multiple valves and infrequent in clinical practice. Moreover, according to a multicenter international database, diabetes mellitus, as presented by our patient, is an independent predictor of endocarditis in-hospital mortality4.
Successful treatment of IE relies on microbe eradication by antimicrobial drugs. Surgery contributes by removing infected material. A difficult aspect of our case was the decision about surgical treatment. In 1961, surgery emerged as a treatment option for IE, and since then its indications have been expanded. Additionally, it has been performed earlier in the disease course5-7.
According to the current American and European guidelines1,8, surgical treatment should be performed in native valve IE when the following indications are present: development of heart failure, especially if moderate or severe; severe aortic or mitral regurgitation with evidence of abnormal hemodynamic status; endocarditis caused by fungi or other resistant organisms; perivalvular infection with fistula or abscess formation; and signs of uncontrolled infection, such as persistent fever and positive blood cultures beyond seven to 10 days of appropriate antibiotic therapy. Other possible indications include embolic events in spite of adequate antibiotic therapy or associated with vegetations larger than 10mm in diameter; and presence of vegetations larger than 10mm in diameter with or without embolic events, if mobile and associated with other signs of severe illness.
Considering right-sided IE, which is more frequent in intravenous drug users, surgery is recommended given the following indications: right ventricular failure due to severe tricuspid valve regurgitation, endocarditis caused by microorganisms difficult to eradicate, and tricuspid vegetations in excess of 20mm in diameter persisting after recurrent pulmonary embolism. Our patient presented severe pulmonary valve involvement, which is not addressed by these criteria.
Although the prognosis of right-sided IE is relatively good with an in-hospital mortality rate of less than 10%1, a vegetation length >20mm was demonstrated to be the main predictor of in-hospital death in a recent large retrospective cohort of right-sided IE9. This was the situation of our patient, in whom the pulmonary vegetation length was >23mm.
Our case illustrated that the approach to patients with IE must be individualized and that all the factors associated with a bad outcome identified at the time of diagnosis should be taken into account10. In fact, in the current case, there were initially no clear indications for surgical intervention. Successive echocardiograms showed preserved systolic function and no signs of fistulas or abscesses. The pulmonary valve, not the tricuspid, presented the most severe insufficiency. The persistent fever could be attributed to a concomitant pulmonary infection uncovered by the antibiotic regimen prescribed, and no new positive blood cultures were obtained; thus, the criteria for defining uncontrolled local infection were not completely fulfilled. The vegetation on the pulmonary valve had a diameter larger than 10mm, was mobile, and was associated with pulmonary embolism; however, the surgical indications concerning the vegetation sizes are not absolute and refer to the native left valves (aortic and mitral).
The periannular extension of the infection in IE is a serious and relatively common complication that is associated with high mortality rate8. It appears to be caused by bacterial invasion and destruction of the local tissue and usually leads to abscess formation. In our case, the TEE was particularly useful in the diagnosis of such lesion. Although surgical intervention is warranted when there is echocardiographic evidence of paravalvular abscess, our patient died before a new surgical intervention could be performed.
The choice of the surgical treatment was based on the unfavorable clinical evolution. The persistent fever could be related to locally uncontrolled infection is spite of the repeated negative blood cultures. In synthesis, our case did not strictly fulfill the clinical and echocardiographic criteria available for surgical indication1,8.
In conclusion, IE has a broad spectrum of presentations, constituting a medical challenge. Important decisions, such as the need and the appropriate time for surgical intervention, do not always find support in the current consensus. Further research and the development of new criteria are necessary to guide medical management in less usual circumstances. The case described here illustrated that although patients at high risk of death may benefit from a more aggressive treatment strategy involving surgery, the infectious process may relapse and in-hospital mortality remains high.
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa do Estado de Minas Gerais (FAPEMIG), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
1. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J 2009;30:2369-2413. [ Links ]
2. Di Filippo S, Delahaye F, Semiond B, Celard M, Henaine R, Ninet J, et al. Current patterns of infective endocarditis in congenital heart disease. Heart 2006;92:1490-1495. [ Links ]
3. Gersony WM, Hayes CJ, Driscoll DJ, Keane JF, Kidd L, O’Fallon WM, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation 1993;87 (suppl 1):I-121-I-126. [ Links ]
4. Kourany WM, Miro JM, Moreno A, Corey GR, Pappas PA, Abrutyn E, et al. Influence of diabetes mellitus on the clinical manifestations and prognosis of infective endocarditis: a report from the International Collaboration on Endocarditis-Merged Database. Scand J Infect Dis 2006;38:613-619. [ Links ]
5. Aksoy O, Sexton DJ, Wang A, Pappas PA, Kourany W, Chu V, et al. Early surgery in patients with infective endocarditis: a propensity score analysis. Clin Infect Dis 2007;44:364-372. [ Links ]
6. Thuny F, Beurtheret S, Mancini J, Gariboldi V, Casalta JP, Riberi A et al. The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis. Eur Heart J 2009, Mar 26. [Epub ahead of print] [ Links ].
7. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler Jr VG, et al. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation 2010;121:1005-1113. [ Links ]
8. American College of Cardiology. American Heart Association Task Force on Practice Guidelines. Society of Cardiovascular Anesthesiologist. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2006;48:e1-148. [ Links ]
9. Martin-Davila P, Navas E, Fortun J, Moya JL, Cobo J, Pintado V, et al. Analysis of mortality and risk factors associated with native valve endocarditis in drug users: the importance of vegetation size. Am Heart J 2005;150:1099-1106. [ Links ]
10. Nunes MCP, Gelape C, Ferrari T. Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period: prognostic factors and in-hospital outcome. Int J Infect Dis 2010;14:e394-398. [ Links ]
Dra. Maria do Carmo Pereira Nunes
Deptº Clínica Médica/FM/UFMG
Av. Prof. Alfredo Balena 190
30130-100 Belo Horizonte, MG, Brasil
Phone: 55 31 3248-9746
Fax: 55 31 3248-9664
Received in 21/12/2010
Accepted in 04/02/2011