Heart Block During Bacterial Endocarditis: A Review of the Literature and Guidelines for Surgical Intervention

PULMONARY COCCIDIOIDAL MYCETOMA

ifestations and complications resemble those of pUlmonary aspergillorna. References I . Varkey B, Rose HD: Pulmonary aspergilloma: A rational approach to treatment. Am J Med 1976; 61:626-631. 2. Fraser RG, Pare JAP: Diagnosis of Diseases of the Chest, ed 2. Philadelphia, Saunders, 1978, p 807. 3. Editorial: Pulmonary mycetoma. Lancet 1968; 2:439-441. 4. Weese WC, Helms CM: Trichophyton: A new cause of pUlmonary mycetoma. Am Rev Respir Dis 1973; 108:643-646. 5. Belgrad R: Fungus ball : An unusual manifestation of coccidioidomycosis. Radio11971; 101:289-290. 6. Putnam JS, Harper WK, Greene IF, et al: Coccidioides immitis: A rare cause of pulmonary mycetoma. Am Rev Respir Dis 1975; 112:733-738. 7. Bayer AS, Yoshikawa IT, Galpin lE, et al: Unusual syndromes of coccidioidomycosis: Diagnostic and therapeutic considerations. Medicine 1976; 55:131-152. 8. ThadepalJi H, Salen AF, Mandai AK, et a1: Pulmonary mycetoma due to coccidioides immitis. Chest 1977; 71:429-430. 9. Fee HI, McAvoy 1M, Michals AA, et al: Unusual manifestation of coccidioides immitis infection. J Thorac Cardiovasc Surg 1977; 74:548-550. 10. Nelson AR: The surgical treatment of pulmonary coccidioidomycosis. Curr Probl Surg Oct 1974; 1-48. II. Drutz Dl, Catanzaro A: Coccidoidomycosis. Am Rev Respir Dis 1978; 117:559-585, 727-771. 12. Puckett TF: Hyphae of coccidoides immitis in tissues ofthe human host. Am Rev Tuberc 1954; 70:320-327. 13. Eckmann BH, Schaefer GL, Huppert M: Bedside interhuman transmission of coccidioidomycosis via growth on fomites. Am Rev Respir Dis 1964; 89:175-185. .

Heart Block During Bacterial Endocarditis: A Review of the Literature and Guidelines for Surgical Intervention MARK JOSEPH DINUBILE, M.D.

carditis in whom first degree heart block developed and then disappeared over five days; she was successfully managed with medical therapy alone. This case illustrates that some patients with endocarditis and heart block will not require surgery. In this setting, I propose the following guidelines in selecting patients for operation: 1) the observed appearance or progression of heart block; 2) the presence of aortic valve involvement; 3) the persistence of heart block, despite at least one week of optimal antibiotics; and 4) the elimination of other potential causes of conduction abnormalities. KEY INDEXING TERMS: Endocarditis; Heart block; Myocardial abscess; Surgery. [Am J Med Sci 1984; 287(3):30-32.) Bacterial endocarditis is infrequently associated with atrioventricular (AV) conduction block, with a reported frequency ranging from 0% to 14%.1-7 The incidence may be significantly higher in prosthetic endocarditis as opposed to native valve infection .2.8 ,9 Conduction disturbances in the setting of aortic endocarditis have been correlated with valve ring disruption and deep myocardial abscesses at surgery and autopsy.4,10-12 Despite the necessarily biased selection of patients included in these studies, many authors have recommended that AV block developing during active aortic valve endocarditis be considered ali indication for prompt surgical intervention. 12-15 In the absence of a prospective study, an aggressive surgical approach to certain patients with endocarditis and heart block may be most appropriate at this time; however, overgeneralization of this recommendation to all such patients may interfere with optimal management. For example, although the occurrence of complete heart block (CHB) during aortic valve endocarditis has been consistently associated with myocardial abscesses at necropsy,IO,I6 the data base upon which to build an approach to AV block in patients with mitral valve infection is much less finn. Likewise, one is less secure in extrapolating from CHB to first degree 00) block, although there exists evidence that simple PR prolongation in aortic endocarditis may bear an ominous prognosis.1 6 Lastly, heart block can be secondary to drugs, infarction or myocarditis,17-22 and, under such circumstances, may be transient l and responsive to medical therapy alone,23 analogous to early cerebritis before frank brain abscess. 24 ,25 I wish to report an illustrative case of combined mitral and aortic endocarditis complicated by transient 1° heart block, and subsequently define the indications for surgery in patients with endocarditis and AV conduction block. Case Report

Abstract: The management of patients with bacterial endocarditis complicated by atrioventricular block is based on uncontrolled data, mostly from retrospective surgical and autopsy series. It is difficult to advance broad recommendations on the basis of such a biased population. Nevertheless, it is the firm opinion of many experienced clinicians that heart block developing as the result of aortic endocarditis signals myocardial abscess formation, and thereby is an indication for early surgery. I present a patient with aortic and mitral endo-

From tire Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital. Boston. Tire author thanks Mrs. Nancy DiNubile and Dr. David Henry for tlreir insightful advice and generaus support. Reprint requests: Dr. Mark DiNubile. Hematology-Oncology Unit. Cox Building. Sixth Floor. Massachusetts General Hospital, Boston, MA 02114. 30

A 20-year-old white woman was admitted after five months of fever, arthralgias, and malaise. She had been in excellent health until six months prior to admission (PTA) when she underwent an uneventful dental examination and cleaning. About one month later, she developed generalized myalgias and arthralgias, as well as a stiff neck and retro-orbital pain. She felt she had a "viral syndrome" and recovered almost completely in less than a week; however, she never fully regained her energy or appetite. Three months PTA she nearly fainted, and this event prompted her to see her family physician. At that time, her examination was remarkable only for tachycardia; her blood tests showed a moderate neutrophilic leukocylosis with a slight anemia, and her urinalysis was benign. Shortly thereafter, she developed episodic night sweats and low-grade fevers; additionally, she complained of aching and swelling of various joints, most prominenlly knees and ankles. 1\vo days PTA she again sought medical advice and was subsequently admitted. On admission, her temperature was 102°F, a systolic murmur was audible near the left sternal border, and hepatomegaly without a MAY/JUNE 1984 VOLUME 287 NUMBER 3

DINUBILE

palpable spleen was detected. Her laboratory examination revealed a hemoglobin of 9g per dL, a white blood count of 7,500 per mm3 , a urinalysis remarkable for hematuria and pyuria but without cellular casts, a nonnal chest radiograph, and a totally nonnal electrocardiogram (EKG) with a heart rate of 96 beats per minute and PR interval of .18 seconds. Four sets of blood cultures drawn over a 24hour period grew a-hemolytic Streptococcus sanguis; the minimal inhibitory and bactericidal concentrations to penicillin were less than 0.1 mcg per ml. Late on the second hospital day, she was begun on intravenous penicillin (20 million units per day) and gentamicin (3 mg per kg per day). M-mode and two-dimensional (20) echocardiograms revealed vegetations on both the aortic and mitral valves. On the third hospital day, a new decrescendo diastolic munnur was heard in the aortic area and along the sternum; in addition , her EKG showed a PR interval of .20 seconds with a heart rate of 92 beats per minute. She was transferred to the medical intensive care unit, where the gentamicin was discontinued. On the following day, the PR interval lengthened to .24 seconds and by the sixth hospital day had further prolonged to .28 seconds, with a heart rate of 88 beats per minute. There were no other EKG changes. She was receiving only intravenous penicillin and chloral hydrate. By the seventh hospital day, she was afebrile, comfortable, without symptoms or signs of heart failure, and generally felt much improved. There were to be no further auscultatory changes in her heart munnurs. Another EKG demonstrated a PR interval of .26 seconds. 1Wo days later, the PR interval had shortened to .18 seconds with a heart rate ofn beats per minute. The remainder of her course was without complications. Her physical examination and repeat EKGs and echocardiograms demonstrated no further changes. Four months after discharge, she was able to perform all her usual activities. Her private doctor reports she has continued to do well; her most recent outpatient visit was nine months after discharge, at which time her physical examination, chest radiograph, EKG and echocardiograms were unchanged.

Discussion There are several important features of this case that pertain to the role of surgery in active endocarditis. Although the pathogen here was an exquisitely penicillin-sensitive viridans streptococcus, this fact clearly did not guarantee the success of medical therapy. 26.27 On the other hand, the demonstration of left sided vegetations by both M-mode and 20 echocardiography did not preclude successful medical treatment. 28 •29 Perhaps the most worrisome aspect of this patient's course was the progressive increase in the PR interval in the presence of a new aortic regurgitant murmur,12 suggesting annular disruption with valve ring abscesses. 10 The transient 1° heart block serves as a caution that, before heart block is accepted as evidence of organized myocardial abscesses and, therefore, as an indication for surgery, the electrocardiographic findings should persist. The critical period of observation is difficult to ascertain , but a minimum period of five days seems reasonable, as illustrated by this case. Perhaps constancy of the PR prolongation for at least three days of maximal antibiotic therapy would more accurately predict the irreversibility of the process and, thus, true abscess formation. However, it appears that fluctuation of the degree of heart block, even with eventual normalization of AV conduction, may still be associated with other complications and a high mortality rate. 1 Unfortunately, any guidelines offered at this time are largely speculative and deserve more careful study. It should be emphasized that heart block may result from noninfectious etiologies, such as digoxin administration or myocardial infarction. Every effort must be made to uncover such potential causes, for example, discontinuing or reducing suspected drugs and rechecking EKGs and cardiac enzymes to detect evidence of myocardial ischemia or infarction. Obviously, the presence of certain drugs andlor infarction does not eliminate the possibility of coexisTHE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

tent myocardial abscesses, but these circumstances substantially reduce the probability that the conduction delay is the result of deep tissue infection. Equally apparent is that normal AV conduction does not rule out myocardial abscesses. TIssue invasion should be suspected in the presence of a changing aortic diastolic murmur, persistent unexplained fever despite appropriate antibiotics, purulent or grossly hemorrhagic pericarditis, and major changes in hemodynamic status.4.9.10.12.13.15.17.23.30-34 Valve replacement in the patient with annular abscesses is difficult, but the problems are not insurmountable. 4.10 Dehiscence ofthe prosthesis occurs more frequently when valve ring abscesses are found at surgery, although the regurgitant volume is often hemodynamically inconsequentia1. 4 Increasingly sophisticated operative techniques 35 may further reduce this complication. Major loosening of the valve can sometimes be corrected by a second valve replacement. Recrudescent infection on the newly implanted prosthetic valve may also develop more commonly when extensive perivalvular infection is present at the time of surgery, but this problem has not proven to be of great magnitude. Conduction disturbances manifested as right or left bundle branch block (BBB) during aortic endocarditis have been less well studied; however, such findings may indicate septal abscesses and possible perforation. 10.16 Patients with BBB appear to constitute a high risk groUp16; such may also apply to patients who develop a variety of arrhythmias, including supraventricular tachycardias, ventricular ectopy, and ventricular tachycardia during active endocarditis. Many reports have noted the association of myocardial abscesses with virulent organisms such as Staphylococcus aureus and Streptococcus pneumoniae. 34 •36 Patients infected with these pathogens may be more likely to develop locally invasive disease and, consequently, heart block. A recent autopsy study, 10 however. failed to demonstrate any significant differences between patients with and without valve ring abscesses as to the types of causative organisms. Clearly, certain strains of viridans streptococci can invade myocardium. 26 •27 In an individual case, identification of the specific organism is of little utility in defining the etiologic mechanism of the conduction delay. Conclusions The rationale behind surgical intervention in patients with endocarditis and heart block rests on two uncontrolled observations: 1) new or changing conduction defects imply myocardial abscess formation; and 2) this situation requires surgery for cure in most, if not all, patients . These reasonable assumptions deserve prospective evaluation, and final recommendations would be premature at present. Nevertheless, since patients are often afflicted by such unresolved problems before controlled studies (if forthcoming) are performed, I offer the following tentative guidelines. Surgery should be strongly considered in any patient with endocarditis and AV block if: 1) the conduction defect is observed to develop or progress during the hospitalization for the endocarditis (and not simply inferred to be new by comparison to past EKGs): 2) the aortic valve is clearly involved with infection (as demonstrated by a new or changing aortic diastolic murmur andlor echocardiographic visualization of aortic vegetations); 3) the heart block fails to improve after several days to one week of optimal medical therapy; and 4) no other potential cause for the conduction abnormality can be identified. The proper management of heart block during endocarditis exclusively of the mitral valve is difficult to determine from the literature. In necropsy studies of valve ring abscesses, the overwhelming majority of cases involve the aortic valve. 10 .17 Accordingly, some authors have been cautious about recommending surgery for conduction block in mitral valve endocarditis, while 31

HEART BLOCK DURING ENDOCARDITIS

accepting persistent heart block during aortic valve endocarditis as an indication for early operation. IS It is clear, however, that conduction disturbances and a variety of arrhythmias may develop when the mitral valve alone is infected. 12.13 At present, careful observation of patients with pure mitral valve endocarditis and heart block, if otherwise uncomplicated, seems reasonable; as further data accrue, a more aggressive surgical approach may prove optimal. If the decision to operate is reached, prompt surgery is advocated, since annular abscesses may lead to rapid, unexpected, and often catastrophic decompensation.4.lo.13.ls Prolonged delays in order to administer more antibiotics may increase mortality and morbidity.4.lo.37 Careful monitoring of these patients, preferably in an intensive care unit, is recommended once heart block is noted, because CHB may develop suddenly. 1,4.16 Prophylactic insertion of a pacemaker merits consideration. In certain cases, other means of detecting myocardial abscesses might be undertaken, but echocardiography, nuclear scanning, and cardiac catheterization have not proven consistently useful in demonstrating tissue invasion. 23 .38 -40 Of course, clinical clues that deep tissue infection has occurred, as well as the presence of other surgical indications,ls cannot be ignored.

References I. Wang K, Gobel F, Gleason DF, et al: Complete heart block complicating bacterial endocarditis. Circulation 1972; 46:939-947. 2. Rabinovich S, Evans J, Smith 1M, et al: A long-tenn view of bacterial endocarditis: 337 cases, 1924-1963. Ann Intern Med 1965; 63:185-196. 3. Pearce ML, Guze LB: Some factors affecting prognosis in bacterial endocarditis. Ann Intern Med 1961; 55:270-278. 4. Stinson EB: Surgical treatment of infective endocarditis. Prog Cardiovasc Dis 1979; 23:145-169. 5. Shineboume EA, Cripps CM, Hayward GW, et al: Bacterial endocarditis 1956-1965: Analysis of clinical features and treatment in relation to prognosis and mortality. Br Heart} 1969; 31:536-547. 6. Von Reyn CF, Levy RB, Arbeit RD, et al: Infective endocarditis: An analysis based on strict case definitions. Ann Intern Med 1981; 94:505-517 . 7. Penton GB, Miller H, Levine SA: Some clinical features of complete heart block. Circulation 1956; 13:801-812. 8. Madison J, Wang K, Gobel FL, et al: Prosthetic aortic valvular endocarditis. Circulation 1975; 51:940-949. 9. Anderson OJ, Bulkley BH, Hutchins GM: A clinicopathologic study of prosthetic valve endocarditis in 22 patients: Morphologic basis for diagnosis and therapy. Am Heart} 94:325-332. 10. Arnett EN, Roberts WC: Valve ring abscess in active infective endocarditis: Frequency, location and clues to clinical diagnosis from the study of 95 necropsy patients. Circulation 1976; 54:140-145. II. Mildvan D, Goldberg E, Berger M, et al: Diagnosis and successful management of septal myocardial abscess: A complication of bacterial endocarditis. Am} Med Sci 1977; 274:311-316. 12. Hutter AM, Moellering RC: Assessment of the patient with suspected endocarditis. }AMA 1976; 235:1603-1605. 13. !
23. Wilson WR, Giuliani ER, Danielson GK, et al: Management of complications of infective endocarditis. Mayo Clin Proc 1982; 57:162-170. 24. Heineman HS, Braude AI, Osterholm JL: Intracranial suppurative disease: Early presumptive diagnosis and successful treatment without surgery. }AMA 1971; 218:1542-1547. 25. Brewer NS, MacCarty CS, Wellman WZ: Brain abscess: A review of recent experience. Ann Intern Med 1975; 82:571-576. 26. Meshel JC, Wachtel HL, Graham J: Bacterial endocarditis presenting as heart block. Am} Med 1970; 48:254-255. 27. Hosea SW: Vtrulent Streptococcus viridans bacterial endocarditis. Am Heart} 1981; 101:174-176. 28. Stewart JA, Silimperi D, Harris P, et al: Echocardiographic documentation of vegetative lesions in infective endocarditis: Clinical implications. Circulation 1980; 61:374-380. 29. Strom J, Becker R, Davis R, et al: Echocardiographic and surgical correlations in bacterial endocarditis. Circulation 1980; 62(suppl):I164-1l67. 30. Katz D, Cooper JA, Frieden J: Bacterial endocarditis presenting as complete heart block with paradoxical (left-to-right) pulmonary emboli. Am Heart} 1973; 85:108-112. 31. Rubin RH, Moellering RC: Clinical, microbiologic and therapeutic aspects of purulent pericarditis. Am} Med 1975; 59:68-78. 32. Sanson J, Slodki S, Gruhn JG: Myocardial abscesses. Am Heart} 1963; 66:301-308. 33. Ryon DS,Pastor BH, Myerson RM: Abscess of the myocardium. Am} Med Sci 1966; 251:698-705. 34. Utley JR, Mills J: Annular erosion and pericarditis: Complications of endocarditis of the aortic root. } Thorac Cardiovasc SlIrg 1972; 64:76-79. . 35. Lau J, Guinn G, Beall A, et al: Operative techniques in infective endocarditis. Ann Thorac Surg 1981; 32:351-356. 36. Sheldon WH, Golden A: Abscesses of the valve rings of the heart, a frequent but not well recognized complication of acute bacterial endocarditis. Circulation 1951; 4:1-9. 37. Boyd AD, Spencer FC, Isom OW, et al: Infective endocarditis: An analysis of 54 surgically treated patients. } Thorac Cardiovasc Surg 1977; 73:23-30. 38. Melvin ET, Berger M, Lutzker LG, et al: Noninvasive methods for detection of valve vegetations in infective endocarditis. Am } Cardiol 1981; 47:271-278. 39. Riba AL, Downs J, Thakur ML, et al: Technetium 99m stannous pyrophosphate imaging of experimental infective endocarditis. Circulation 1978; 58:111-1I9. 40. Mills J, Abbott J, Utley JR, et al: Role of cardiac catheterization in infective endocarditis. Chest 1977; 72:576-582.

Membrane Plasma Exchange in Goodpasture's Syndrome FRIEDER KELLER, M.D., GERDOFFERMANN, M.D., GEORG SCHULTZE, M.D., KARL WAGNER, M.D., EBERHARD AULBERT, M.D., J{JRGEN SCHOLLE, M.D., ULRIKE FABER, M.D., MAHAMANE MAIGA, M.D., AND WOLFGANG POMMER, M.D.

Abstract: We report two cases with Goodpasture's syndrome successfully treated by membrane plasma exchange. In both patients, pulmonary infiltrations and hemoptysis had already resolved after the first pulse methylprednisolone dose (1000 mg IVJ. Following plasma exchange. renal function did not further deteriorate in one patient and returned to normal in MAY/JUNE 1984 VOLUME 287 NUMBER 3