Diagnoses: Infective endocarditis (methicillin resistant S. aureus), pulmonic valve, congenitally malformed. Infected emboli, lung. Infective pulmonary arteritis. Infected, cavitated infarcts, lung. Disseminated birefringent crystals in lungs, liver, spleen (intravenous drug use). Crack black lung.

Comment: Review of the transesophageal echocardiogram from 5/5 (about 2 mo before death) showed a small (0.7 cm) vegetation on an abnormally thickened pulmonic valve (PV). The diagnosis was probably dismissed because the PV is almost never involved in infective endocarditis (IE). The onset of IE probably coincided with the development of the septic arthritis. Death was ascribed to respiratory failure from septic emboli, infarcts, and pneumonia.


Infective Endocarditis

Introduction: Infective endocarditis (IE) has a varying epidemiology depending on individual risk factors present in a given population. The frequency of various types of congenital, acquired, and degenerative cardiac valve diseases, intravenous drug use, diabetes, and malignancy contributes to the incidence of disease in a population. Other predisposing factors include localized chronic infections, alcoholism, splenectomy, and immunosuppression [1]. Further, a high autopsy rate is important for diagnosis of cases that are missed clinically [2,3]. Outcome of IE depends on the particular organism involved, as well as on early diagnosis and treatment [1]. A uniformly fatal disease in the preantibiotic era, it has changed to one with a mortality rate of around 40% when caused by S aureus [1], but there are wide variations in mortality rates depending on valve(s) and organism involved. Complications are associated with considerable morbidity. Not all cases are community-acquired as nosocomial IE may occur in the setting of intravascular or intracardiac catheters [1,2]. It is still useful to separate the clinical syndromes of acute and subacute endocarditis on the basis of predisposing cardiac disease, virulence of the organism, and severity of the symptoms, despite some overlap [1]. Host factors and organisms in acute endocarditis have been discussed recently in two reviews: one summarizes the literature [1], and the other describes the disease in a Swedish city of 428,000 from 1984 to 1988 [3]. Here, discussion will focus first on the acute disease, in general, and then on aspects of the disease in intravenous drug users (IVDUs).

Clinical features: Ordinarily, the disease presents with high fever, chills, and malaise. The classic new or changing murmur, however, can be absent in up to a third of cases. There may be left ventricular failure. Extra-cardiac features of left-sided valve involvement include stroke, acute mental status change, meningitis, arthralgia, osteomyelitis, septic arthritis, splenic infarct, renal abscess, and Janeway lesions (non-tender red spots on the palms or soles). Extra-cardiac manifestations of right-sided valve involvement include dyspnea, cough, pleurisy, and hemoptysis caused by septic infarcts, pneumonia, or empyema. Laboratory findings include blood cultures positive for virulent organisms, leukocytosis, hematuria, pyuria, and increased sedimentation rate [1]. Pulmonary radiographic findings with right-sided endocarditis include multiple rounded opacities, cavitating masses, and pleural effusions [1].

Diagnosis: Criteria based on clinical findings alone [4] have recently been expanded to incorporate echocardiographic features (table), which have increased the sensitivity of making a diagnosis [5].


Table 1: Duke Criteria for IE [5]

Major criteria: a) positive blood cultures of a designated number and with an appropriate type of organism, b) positive echocardiogram with specific features

Minor criteria: a) predisposition: cardiac abnormality or IVDU, b) fever, c) vascular manifestations, d) immunologic features, e) other microbiologic or echocardiographic evidence

Definite diagnosis rests on 2 major, 1 major and 3 minor, or 5 minor criteria.

Cases not completely rejected are diagnosed as possible IE and treated on the basis of clinical judgment.


Diagnosis continued: Clinically, exclusion of a non-cardiac source of bacteremia, persistent bacteremia with typical organisms, fever >38°, cardiac murmur, history of cardiac procedure or device, consistent septic emboli, and otherwise unexplained peripheral manifestations suggest the diagnosis [1]. Transesophageal echocardiography (TEE) that is performed by an experienced echocardiographer, with or without a preceding transthoracic echocardiogram (TTE), can diagnose a vegetation or myocardial abscess in over 90% of cases [1,6]. Simultaneous Doppler studies demonstrate abnormal flow patterns of fistulas and valve perforations. Imaging of the PV can be difficult in the transverse plane with TEE, but use of a biplane probe to show a longitudinal view of the outflow tract improves the diagnostic usefulness [7]. A recent report found that the diagnosis of IE relied on clinical findings in only 7% of 103 patients with S aureus bacteremia. In contrast, 26% had findings of IE by TEE [2]. For neurologic findings, head CT ± MR to detect infarcts or abscesses, and cerebral arteriography to detect mycotic aneurysms are further diagnostic adjuncts [1].

Differential diagnosis: Infected hemodialysis shunts, suppurative thrombophlebitis, septic arthritis, and skin or other abscesses can cause bacteremia and pulmonary lesions without endocarditis. Further, patients with IVDU may not have classic findings of IE, as in the patient presented here [1].

Histologic changes: In general, vegetations of acute IE occur on normal valves and are large and friable, whereas those of subacute IE occur on fibrotic valves and tend to be small. Factors predisposing to subacute IE are the sterile platelet-fibrin thrombi that develop during the remodeling of previously-damaged valves. Adherence of bacteria in the presence of agglutinating antibody initiates the vegetation, which in both types of IE is composed of a proteinaceous coagulum with embedded inflammatory cells and bacteria. With time, organization and calcification may occur, especially in subacute disease. The vegetations may cause perforation of valve leaflets or rupture of chordae tendineae. Spread of infection to the myocardium can lead to abscesses or fistulas between chambers or to the pericardium. Systemic emboli most frequently involve the brain, spleen, coronary arteries, and kidneys. Besides producing infarcts or abscesses, mycotic aneurysms may develop and rupture to produce hemorrhage. Septic emboli from the right heart to the lungs may be accompanied by hemorrhages or infarcts that usually become infected and may then cavitate [1].

Treatment: Antibiotic therapy may be curative. When antibiotics fail, indications for surgical therapy include severe congestive heart failure, persistent infection, embolic complications, myocardial abscess, and valve perforation or dehiscence of a prosthetic valve [1].

Outcome: The mortality rate for IE is dependent on many factors as indicated above. In one small study, factors predicting death included systemic embolism, paravalvar abscess, S aureus endocarditis, and antibiotic treatment alone. Risk of embolization increased with the total length of the vegetations measured by TEE [8]. Five-year survival after valve replacement for IE is 47 to 71% in the non-IVDU population [1].

IE in IVDUs: A report from Cook County Hospital, Chicago, describes the disease in 125 episodes of native valvar IE in IVDUs during a 4-year period from 1988 to 1991 [9]. These cases accounted for 94% of all IE cases seen at that hospital during that time. Salient features are tabulated below.

Table 2: Summary of Characteristics of IVDUs with IE [9]

Gender

M:F 2:1

Age, mean

37 years (range 23-59)

Other predisposing factors

Past IE (22%), rheumatic heart disease (2%)

Signs

Fever >37.8° C (83%), cardiac murmur (70%), anemia (38%), hepatomegaly (30%), splenomegaly (11%), microhematuria (47%)

HIV+/HIV-/unknown

25%/36%/39%

Organisms

S aureus (67%, of which 15% were methicillin resistant),
Streptococcus (26%, of which 63% were S viridans)

Organisms by valve affected

S aureus

TV 60%*, MV 20%, AV 12%, multiple valves 16%

Streptococcus

TV 22%, MV 56%*, AV 25%, multiple valves 12% *Significantly different from other valves.

Any right-sided valve involvement

47%

Any left-sided valve involvement

58% (right & left-sided difference not significant)

Treatment and outcome

82% medical with 9% inhospital deaths

18% medical + surgical with 9% inhospital deaths

About 70% had a major cardiovascular complication

Outcome by valve involved (extremes only)

Tricuspid valve

16% had surgery or died without surgery

Aortic valve

63% had surgery or died without surgery (P = 0.02)

Non-fatal complications

Congestive heart failure (19%), stroke (11%), other systemic emboli (16%), septic pulmonary emboli (66% of those with right-sided vegetations)

HIV infection and IVDU: Another study contrasted the site of infection in 102 IVDUs in Cook County with (45) and without (57) HIV infection (diagram). The differences between HIV-positive and negative patients for location of the endocarditis were significant. S aureus was the most common pathogen in both groups [10]. S aureus was more likely to affect the TV, and streptococci were more likely to affect the MV. IE of the PV is vanishingly rare. Review of valves involved by IE in 449 IVDUs reported since 1970 found that the pulmonic valve was involved in only 1 case [9].

Pathogenesis of IE in IVDUs: The source of S aureus may be the skin, nose, or throat of the patient, as bacteriophage types from these sites have been shown to be similar to those in isolates from the blood. Other sources of infection in the addict include skin abscesses, osteomyelitis, and septic arthritis [11]. Virulent organisms can infect normal valves. In contrast, in our case, the pathogenesis of disease is probably that proposed for patients with subacute endocarditis: platelet-fibrin thrombi that develop during lifelong remodeling of a congenitally deformed valve trap bacteria when there is a high titer of agglutinating antibody [9].

Outcome: An inhospital death rate of 9% for 125 episodes of IE is given in Table 2. A retrospective study compared the outcome of IE in 45 HIV-positive and 57 HIV-negative IVDUs in Cook County hospitals from 1987 to 1992. Only two of the HIV-positive patients were receiving anti-retroviral therapy, and only 1 was taking prophylaxis for pneumocystis. Age and gender were similar in both groups. S. aureus was the most common pathogen. HIV-negative patients had echocardiographically visible vegetations more frequently than HIV-positive patients (77% vs 56%, respectively), and right-sided valves were involved more frequently in HIV-positive patients, and left-sided valves more frequently in HIV-negative ones (see diagram above). Mortality in the hospital was similar in both groups (8.8% for HIV-negative and 13.3% for HIV-positive), but HIV-negative patients died only if left-sided valves were involved whereas the mortality in HIV-positive patients did not depend on the valve infected. The mortality rate for HIV-positive patients increased with decreasing CD4 count. Of those with CD4 counts <200/µl, 56% died; no deaths occurred if the count was >500/µl [10]. For those who underwent surgery, non-compliance with anticoagulation and continued IVDU contributed to a high out of hospital mortality [9].

References

1. Cunha B, Gill M, Lazar J. Acute infective endocarditis. Diagnostic and therapeutic approach. Infect Dis Clin N Am 1996; 10:811-834.

2. Fowler Jr V, Li J, Corey G, Boley J, Marr K, Gopal A, Kong L, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol 1997; 30:1072-1078.

3. Hogevik H, Olaison L, Andersson R, Lindberg J, Alestig K. Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study. Medicine 1995; 74:324-339.

4. Von Reyn C, Levy B, Arbeit R, Friedland G, Crumpacker C. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981; 94:505-518.

5. Durack D, Lukes A, Bright D. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994; 96:200-209.

6. Daniel W, Mügge A. Transesophageal echocardiography. N Engl J Med 1995; 332:1268-1279.

7. Winslow T, Foster E, Adams J, Schiller N. Pulmonary valve endocarditis: improved diagnosis with biplane transesophageal echocardiography. J Am Soc Echocardiogr 1992; 5:206-210.

8. Lancellotti P, Galiuto L, Albert A, Soyeur D, Piérard L. Relative value of clinical and transesophageal echocardiographic variables for risk stratification in patients with infective endocarditis. Clin Cardiol 1998; 21:572-578.

9. Mathew J, Addai T, Anand A, Morrobel A, Maheshwari P, Freels S. Clinical features, site of involvement, bacteriologic findings, and outcome of infective endocarditis in intravenous drug users. Arch Intern Med 1995; 155:1641-1648.

10. Pulvirenti J, Kerns E, Benson C, Lisowski J, Demarais P, Weinstein R. Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression. Clin Infect Dis 1996; 22:40-45.

11. Ang-Fonte G, Rozboril M, Thompson G. Changes in nongonococcal septic arthritis: drug abuse and methicillin-resistant Staphylococcus aureus. Arthritis Rheum 1985; 28:210-213.

Clinical summary

Comments: mw6825@itsa.ucsf.edu

Table of Contents

Last revised 12/10/98

Copyright 1998 by Martha L. Warnock. All rights reserved.