ORIGINAL ARTICLE
Sudden Death as a Complication of Bacterial Endocarditis Angela Byramji, MBBS,* John D. Gilbert, FRCPA,Þ and Roger W. Byard, MBBS, MD*Þ
Abstract: Three cases are reported to demonstrate the range of possible lesions and wide variation in lethal mechanisms that may be found in cases of unexpected death subsequently shown to be due to bacterial endocarditis. Case 1: A 36-year-old man was found dead on his bedroom floor surrounded by drug paraphernalia. At autopsy, acute myocardial ischemia was present caused by coronary artery ostial occlusion complicating acute bacterial endocarditis of the aortic valve. Case 2: A 54-year-old man with chronic renal failure was found dead in bed at home. At autopsy, a left middle cerebral artery territory cerebral infarct was present due to septic embolization from bacterial endocarditis involving the aortic valve. Case 3: A 23-year-old man was found collapsed in a pool of blood. At autopsy, upper airway hemorrhage from an arteriobronchial fistula was present caused by septic pulmonary infarction from previous endocarditis of a congenital ventricular septal defect. This report demonstrates that bacterial endocarditis may still be a cause of sudden and unexpected death presenting to forensic mortuaries and that the underlying mechanisms may involve complex sequences of pathological changes that compromise vascular function. Key Words: bacterial endocarditis, embolization, septic infarct, arteriobronchial fistula (Am J Forensic Med Pathol 2011;32: 140Y142)
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nfective endocarditis may be associated with significant mortality due mainly to the interactions of comorbidities and endorgan dysfunction.1 Mycotic aneurysms may uncommonly complicate infective endocarditis leading to vascular rupture or local sepsis.2 Abscesses are another rare complication that may lead to the formation of fistulous tracts. Three cases of sudden death are reported where lethal sequelae of bacterial endocarditis were unexpectedly revealed at autopsy demonstrating the wide range of fatal mechanisms that may be encountered in this condition.
CASE REPORTS Case 1 A 36-year-old man was found dead on his bedroom floor surrounded by drug paraphernalia. External examination of the body revealed no evidence of trauma and no injection sites. At autopsy, the heart was enlarged (638 g) with multifocal areas of fibrous scarring and mottling suggestive of recent ischemic damage. A large amount of vegetation/thrombus material was adherent to the aortic valve with infiltration of the underlying myocardium extending to involve the anterior leaflet of the mitral valve. Both coronary artery ostia were obstructed by Manuscript received May 7, 2008; accepted July 19, 2008. From the *Discipline of Pathology, The University of Adelaide; and †Forensic Science SA, Adelaide, South Australia, Australia. Reprints: Roger W. Byard, MBBS, MD, Discipline of Pathology, Level 3 Medical School North Building, The University of Adelaide, Frome Rd, Adelaide 5005, Australia. E-mail:
[email protected]. Copyright * 2011 by Lippincott Williams & Wilkins ISSN: 0195-7910/11/3202Y0140 DOI: 10.1097/PAF.0b013e31821984fb
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vegetations. Histological examination of the lesion on the aortic valve revealed organizing thrombus with focal areas of acute inflammation and microabscess formation. Gram staining showed numerous colonies of gram-positive coccobacilli. Areas of chronic, organizing, and acute ischemic change were identified within the heart. Toxicological examination of blood revealed nontoxic levels of methamphetamine, diazepam, and tetrahydrocannabinol. Death was due to myocardial ischemia caused by coronary artery ostial occlusion complicating acute bacterial endocarditis.
Case 2 A 54-year-old man was found dead in bed at home. He had a medical history that included hypertension, type 2 diabetes mellitus, peripheral vascular disease, and chronic renal failure. At autopsy, hemorrhagic infarction of the left middle cerebral artery territory was found with cerebral edema, marked uncal notching, and midline shift. Histological examination of the brain showed focal cortical microabscesses with small vessels containing karyorrhectic debris with neutrophils and occasional gram-positive cocci. The heart was enlarged (527 g) with fibrinous vegetations that on microscopy were also found to contain gram-positive cocci. Death was due to a left middle cerebral artery territory cerebral infarct due to septic embolization from bacterial endocarditis involving the aortic valve.
Case 3 A 23-year-old schizophrenic man was found collapsed outside a house surrounded by a pool of blood. The case was treated as suspicious by attending police officers; however, external examination of the body did not reveal any significant injuries. At autopsy, there was blood within the upper aerodigestive tract with widespread hemoaspiration into both lungs, predominantly involving the right lower lobe. This was associated with a consolidated area around the right lower lobe bronchus and adjacent lower lobe branch of the right pulmonary artery with a 2- to 3-mm diameter fistula running between the artery and bronchus. There was also blood within the mouth and a large amount of blood within the stomach, duodenum, and small intestine. Histological examination of the fistula showed inflammatory granulation tissue, which was capped focally with fibrinous exudate containing an acute inflammatory infiltrate and occasional small colonies of gram-positive cocci between the lumina of the pulmonary artery and the bronchus. Laminated blood clot with a postmortem overgrowth of gram-positive cocci protruded into the lumen of the bronchus. Other findings at autopsy included a small patent septal defect in the lower anterior aspect of the interventricular septum with no evidence of active endocarditis. There were no valvular vegetations. There were no sources of hemorrhage within the mouth, pharynx, esophagus, stomach, or small intestine. There was no evidence of trauma, nor were there other underlying organic illnesses that could have caused or contributed to death. Death was attributed to exsanguination from an arteriobronchial fistula complicating a pulmonary abscess. Am J Forensic Med Pathol
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Subsequent review of the medical history revealed a 6-week admission to hospital 4 months before death with bacterial endocarditis due to Staphylococcus aureus complicating a congenital ventricular septal defect. Echocardiography had shown a large vegetation protruding into the right ventricle, which had shed emboli into both lungs causing septic infarcts with abscess formation. Antibiotic therapy had been successfully undertaken, although follow-up computed tomography scans and chest x-rays showed persistence of a soft-tissue opacity in the hilum of the right lung. A computed tomographyYguided biopsy of the mass was being planned. Anesthetic complications associated with attempted resuscitation in this case involving systemic air embolism through the patent ventricular septal defect have been previously reported.3
DISCUSSION Infective endocarditis may be subclassified into acute and subacute forms. Acute endocarditis is characterized by highgrade fever associated with rapid cardiac damage and metastatic infection of extracardiac sites via the circulatory system. Death occurs within weeks without treatment. Subacute endocarditis is more slowly progressive unless complications such as a mycotic aneurysm arise.1 One of the difficulties of treatment lies in completely eradicating septic loci, as responsible organisms may lie deep within vegetations and antibiotic resistance is increasing.4 The clinical characteristics of infective endocarditis have changed significantly since the description by Osler5 with an increase in the age at onset and some studies now reporting that the most common etiological agent is S. aureus,6,7 although others have found that viridans streptococci are still a major pathogen.4,8 The increasing numbers of patients seen with S. aureus endocarditis may be related to increasing use of intravascular lines/devices, recreational drugs, and prosthetic heart valves.1,7 Degenerative aortic and mitral valve disease now predominates over rheumatic heart disease as the underlying abnormality,9 and a study by Hoen et al7 reported that 47% of patients with infective endocarditis presented without knowledge of a preexisting cardiac disorder. Although it has been reported that the incidence of endocarditis has remained stable,7,8 others have asserted that the incidence is in fact increasing.4 The incidence does vary geographically among different patient cohorts because of associated risk factors, with, for example, intravenous drug users having an estimated 7-fold greater risk than patients with rheumatic heart disease or prosthetic valves.4 In the reported cases, endocarditis was associated with drug abuse, chronic renal failure, and a congenital cardiac defect. Organisms promote the formation of vegetations by inducing platelet aggregation and activating the clotting cascade resulting in layers of fibrin being deposited along with bacteria. Although organisms deep within vegetations may be metabolically inactive, organisms on the surface proliferate and are continuously shed into the circulation.1,4 Mortality rates vary depending on the type of organisms and the underlying pathology with lethal mechanisms involving both cardiac and extracardiac pathology. Cardiac complications include acute congestive cardiac failure from perforated native or bioprosthetic valve leaflets, rupture of infected chordae tendineae, valvular obstruction from bulky vegetations, or sudden intracardiac shunts from fistulous tracts or prosthetic dehiscence. Acute congestive cardiac failure occurs more commonly in native aortic valve endocarditis. Congestive cardiac failure resulting from deterioration of valvular and ventricular function is the most important predictor * 2011 Lippincott Williams & Wilkins
Sudden Death and Bacterial Endocarditis
of adverse outcome requiring surgical therapy.10 Periannular infections are associated with increased mortality and cardiac failure, with a need for surgery, and are found in 10% to 40% of native valve and 45% to 100% of prosthetic valve infections. Common sequelae include perivalvular cavities and abscesses that can cause conduction disturbances especially heart block, which is frequently seen in native aortic valve infection.10 Rarely, abscesses can progress to form fistulous intracardiac tracts.11 As in cases of acute rheumatic fever, coronary artery embolization of fragments of vegetations may occur with resultant myocardial ischemia.12 In case 1, direct occlusion of coronary artery ostia had resulted in lethal ischemia. Extracardiac complications include systemic embolization in 22% to 50% of cases found primarily with aortic and mitral valve infections due to S. aureus, Candida, the HACEK group of gram-negative bacilli (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella spp), and Abiotrophia organisms.10 Embolization most commonly occurs within the first 2 to 4 weeks of antibiotic treatment, with the rate of events during the first 2 weeks dropping from 13 to less than 1.2 embolic events per 1000 patient-days. However, embolic events may occur before diagnosis or even after completion of therapy. The central nervous system is the most common site for embolic complications, with more than 90% of emboli lodging in the middle cerebral artery distribution, as in case 2. After embolization, mycotic aneurysms may occur in 2% to 25% of patients with intracranial aneurysms having a high overall mortality rate of 60%, which increases to 80% with rupture.10 In case 3, pulmonary abscesses had most likely resulted from direct seeding by infected emboli. Bland emboli may result in aseptic infarction and are a well recognized complication in the spleen, with infarction occurring in 40% of left-sided cases of infective endocarditis. However, of those, only approximately 5% will develop splenic abscess.10 The presence of a ventricular septal defect in the reported case had resulted in formation of a fibrin-platelet vegetation on the right side of the defect with embolization via the pulmonary artery. Persistence of the infection despite apparently adequate antibiotic cover resulted in necrosis of the walls of a major airway and artery and intervening connective and pulmonary tissues. Fistula formation
TABLE 1. Causes of Unexpected Death in Cases of Infective Endocarditis Cardiac Acute congestive cardiac failure Heart block Fistulae, eg, aorta root to cardiac chamber Myocardial infarction Extracardiac Embolic events Organ infarction Mycotic aneurysm rupture Arteriobronchial fistula Neurological Aseptic or purulent meningitis Intracranial hemorrhage Embolic stroke Seizures Encephalopathy Sepsis
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had then resulted in massive hemorrhage into the airways with sudden collapse. Infective endocarditis is a complex clinical entity, and despite advances in diagnosis, prompt antibiotic therapy, and surgical intervention, the mortality has changed little over several decades.11 The reported cases are instructive in demonstrating rare and complex sequences of pathological changes that may lead to unexpected death in individuals with this condition involving vascular compromise. Valvular vegetations had caused direct obstruction of blood flow to the myocardium in 1 case, had compromised cerebral blood flow due to fragmentation and embolization in the second, and had caused ongoing pulmonary sepsis, with erosion of a major pulmonary vessel and airway, in the third. Bacterial endocarditis remains an uncommon condition that may still result in sudden death, the precise mechanisms of which may be understood only after careful delineation at autopsy. Causes of unexpected death in infective endocarditis are listed in Table 1. ACKNOWLEDGMENTS The authors thank the South Australian State Coroner, Mr M. Johns, for permission to publish selected details of these cases. REFERENCES 1. Karchmer AW. Infective endocarditis. Chapter 109. In: Harrison’s Principles of Internal Medicine. 16th ed. Kaspar D, Braunwald E, Hauser S, et al, eds. New York: McGraw-Hill; 2005:731Y740. 2. McCready RA, Bryant MA, Fehrenbacher JW, et al. Infected splenic artery aneurysm with associated splenic abscess formation secondary
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to bacterial endocarditis: case report and review of the literature. J Vasc Surg. 2007;45:1066Y1068. 3. Simes D, Gilbert J. Massive air embolism with pulmonary arterio-bronchial fistula and ventricular septal defect. Anaesth Intensive Care. 1997;25:420Y422. 4. Tak T, Reed KD, Haselby RC, et al. An update on the epidemiology, pathogenesis and management of infective endocarditis with emphasis on Staphylococcus aureus. WMJ. 2002;101:24Y33. 5. Osler W. The Principles and Practice of Medicine. London: Butterworth & Company; 1918:797Y804. 6. Fowler VG, Miro JM, Hoen B, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA. 2005;293:3012Y3021. 7. Hoen B, Alla F, Selton-Suty C, et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA. 2002;288:75Y81. 8. Tleyjeh IM, Steckelberg JM, Murad HS, et al. Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA. 2005;293:3022Y3028. 9. Beynon RP, Bahl VK, Prendergast BD. Infective endocarditis. Brit Med J. 2006;333:34Y39. 10. Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications. Circulation. 1998;98:2936Y2948. 11. Paterick TE, Paterick TJ, Nishimura RA, et al. Complexity and subtlety of infective endocarditis. Mayo Clin Proc. 2007;82:615Y621. 12. Stahl J, Santos LD, Byard RW. Coronary artery thromboembolism and unexpected death in childhood and adolescence. J Forensic Sci. 1995;40:599Y601.
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