VALVULAH HEART DISEASE
Frequency of Ring Abscess and Cuspal Infection in Active Infective Endocarditis Involving Bioprosthetic Valves Daniel J. Fernicola, MD,* and William C. Roberts, MN
When active infective endocardHis (IE) involves a biqmaak valve, the infective process may irr volveonlythecuspsorsewhgringorhoth.We Stlld&d34pathtSWithinfectedbioprostheaes
the infecUon involved ths todeterminewhether alspsorlhgporboth,hecausethesecouldaffectprogno4aInthe5patkntsinwhom activeIEbeganc8OdaysaP&eroperation,thei~ fection involved the cusps only in 2, the ring only in 2, Ivwl both in 1. Ths 25 patients in whom signs andsym@omsofactiveIEappearedMOdays after valve replacement were subdivided into 3 cabgotbbasedontheValvearvalvesreplacsd. In the 15 patients with isolated aortic valve re pbwmsnt, the infection involved the cusps only in 5, the tiag onty in 4 and both in 5. In the 5 pa tientswithisoIatedmitralvalvereplacement,ths infection hwolved the cusps only in 2, the ring only in 1, and both in 3. In ths remaining 7 ps tientq 15 native valves were replaced with b
’ hen active infective endocarditis (lE) involves mechanical prostheses,the infective material is always located in the sewing ring (i.e., the site of attachmentof the prosthesis).1-3When active IE involves a bioprosthesis,the infection may involve only the bioprostbetic cuspsor sewing ring, or both. If the infection involves exclusively the cusps, reopen&ion should eliminate the infection in most patients. If, however, the infection involves the sewing ring, reoperation may not eliminate the infection, and therefore prognosis would be different. We examined 34 patients who had active IE after replacementof 21 cardiac valve with a bioprosthesis to determine anatomically the exact location of the infective material.
W
MEWODS
inclusion and exclusion criteria: Recordsfrom the Pathology Branch of the National Heart, Lung, and Blood Institute were searchedfor patients who had active IE after replacementof 21 cardiac valve with a bioprosthesis. Patients were included in this study if they ~amdlOofthemwefeinfec&dlhei~ had undergone replacementof 21 cardiac valve with a fectiiinvolvedthecuspsonlyIn7,andboththe porcine, bovine or parietal pericardial bioprostbesis (mounted on a stent), and subsequentlyhad 21 episode cuspsandlinghr3. of all 34 patients, l3 had operatlve excision of of active IE, and either died and an autopsy was performed, or the infected bioprosthesis was excised and theinfectedbi~ldiedwithin8Odays ofthebiopnWhe&excidon,andlweslostto examined by us. Patients were excluded from this study if a native cardiac valve was replaced with a homograft followulpg of the remaining 11 patients, 4 died or if vegetations were present on a native cardiac valve late (1.5,3,5 and 14 years), Md the other 7 m that was excised and replaced with a bioprosthesis.If a alive5 to1OyearsafterMoproQthetic excision (all in New Yti Heart A!ssocwonfllnctktnal patient, however,had active IE on a native cardiac valve class I or II). Thug akhough infection limited to and the infection healed before operative excision, the patient was not excluded from this study. ti-z cusps may ream&My allow a reoperation with infection InvolvDivldon of paUsn& Of 34 patients,13(38%) underwent operative excision of the infected bioprostbesis. i1qftheannularti~(8of13reope~tionpatknts) does not prevent successful olltcome. One of the 13 patients died within 24 hours of reopera(Am J cardiol1993;72:3l4-323) tion and his heart was examined at necropsy.A second patient died 5 years after operative excision of the infected bioprosthesis and her heart was examined at autopsy. Of these 13 patients, 5 had the second operation at the Clinical Center of the National Institutes of From the Pathology Branch, National Heart, Lung, and Blood Institute, Health, and 8 had the second operation at Georgetown National Institutesof Health, Bethesda,Maryland. Manuscript received February 5, 1993;revised manuscript received and acceptedMarch 3, University Medical Center.These 13 patients are among 1993. 160 whose operatively excised bioprosthesesare in the *Current address:Division of Cardiology, Department of Medi- collection of the Pathology Branch of the National cine, Georgetown University Medical Center, Washington, DC. Heart, Lung, and Blood Institute. 20058. The remaining 21 patients (61%) never had the intCurrent address:Baylor CardiovascularInstitute, Baylor University Medical Center, 3500 GastonAvenue, Dallas, Texas 75246. fected bioprosthesis operatively excised, and they were
314
THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
AUGUST1,1993
studied at necropsy.The necropsy was performed at the Clinical Center of the National Institutes of Health in 4 patients, at Georgetown University Medical Center in 3, at the Washington Hospital Center,Washington, D.C., in 2, at the District of Columbia Veterans Administration Hospital in 2, and 1 at 10 different medical centers in 1 each. Petiod of study: Of the 34 patients, 6 were studied in the decade 1971to 1980, 27 from 1981to 1990, and 1 in 1991.
120 days (mean 65). It is presumedthat the infection in each of these 5 patients was initiated at the lirst valve replacementor shortly thereafter.Five of the 6 bioprostheses in these 5 patients were infected; the infection was limited to the cuspsin 1 patient and to the ring only in 2, and it involved both the cusps and ring in 2. The other major group included the 29 patients in whom the interval from valve replacement to onset of
Examinersoftheb8rtsandinfectedbioprori-
theses: All 22 hearts with infected bioprostheseswere examined initially by WCR, and 19 were subsequently examined by DJF. Operatively excised infected bioprosthesesin the other 13 patients were examined initially by WCR and all were examined subsequentlyby DE Photographsof infected bioprostheseswere available in 20 of the 22 necropsiedhearts with infected bioprosthesesand in all 13 patients with operatively excised infected bioprostheses. Statistical analysis: Data were analyzed using the Stat View 512+ statistical software package. Categoric comparisons were obtained with 2-tailed &i-squared analysis. Numeric comparisonswere obtained using a 2tailed, unpaired t test. Statistical significancewas defined as p CO.05 RESULTS Specific clinical and necropsy findings in each of the 34 patients are listed in Table I and illustrated in Figures 1 to 13. Patients were divided into 2 major groups. One group included 5 patients whose interval from valve replacementto onset of signs or symptoms, or both, of bioprosthetic endocarditis was ~60 days (range 12 to 32, mean 20) (early infection). The interval from signs or symptoms, or both, of bioprosthetic endocarditis to death or operative excision of the infected biopmsthesis ranged from 6 to 108 days (mean 43), and that between the lirst valve replacementto death (n = 4) or operative excision of the infected bioprosthesisranged from 36 to
FlWREl.Patient5;TableI.C8ddadbicanrbioprocrthetie valve endocarditis in a 63-yeadd white waman (NIH #A88 79)whohadhadmitralandtltcusplllvdve~36 daysbefouudeath.gaviewofthevenbtculaaspectof~ bioproQthetivalveinthetkuspidposlth.lheinfeded sinuses 9, excised mater&l Rlls eadl of the 3 bbpmddc bbpmddsfromthetricu~podtion.c,exclsedbiopos thesisfnnnthemibdposlt&n,whlchlsfmeoflnfecth. LV = Ml venbicuk cavity; VS = ventrlcuk septum.
BIOSPROSTHETIC ENDOCARDITIS 315
584
624
Totals
58
67
29 53
Subtotal
31 30
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days days days days days
endcarditis
T llri Mi T3 Mi 13 “Mi A3 Mi A T
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t A
months months months months months months months
days days days days days
months months months months
months months months months months months months
30 months4
65 months4
36 month+
37 months4
do mnntll4 _ . ._
37 months
9 months
125 months
12 months 9 months
1108 months
96 months
44 months
66 months4
months months months months months months
1088 months
94 months
4 months
42 months4
27 144 84 49 84 3
28 months4
31 4 8 9 6 61 259
173 months
48 72 121 34 37
38 months
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1
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Alpha streptococcus
Alpha streptococcus Staphylococcus epidermidis Staphylococcus aweus yp:; streptococcus
Group D Streptococcus Staphylococcus epidermidis
Alpha streptococcus Negative Alpha streptococcus Peptostreptoccccus~ Alpha streptococcus Kpp streptwxcus
Staphylococcus aure~s Aspergillus fumigatus Staphylococcus epidermidis Staphylococcus aweus Candida albicans
Infecting Organism
= female; Ei,r fib@; H ; HanFock; = surgery; D,> = signs ana symproms;
!I it
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before arrival at hospital; 8necmsis limited to antibiotics before blood cultures. 15indi&ion died 24 hours after surgery; &ing abscess
4
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> 60 days after initial valve replacement)
43 days4
43 39 89 120 36
28 months4 26 108 36 48 84 3
Stenosis
Biopmsthetic
< 60 days after mitral valve replacement)
Interval 1st VR to Deathl2d VR
36 months
30 3 7 3 4 60 255
153 months
months months months months
endocarditis
I? A A A t
47 56 120 32 36
of bioprosthetic
20 days4
21 32 14 12 20
of bioprosthetic
Interval VR to S/S of BPE
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+diastinal infection; 2pseudomonas aeru#inOsa grown from sternal wound and blood 1 week before death; 3bioprosthesis not infected; 4median; %ctinobacillus grown from blood cultures; 6valve dehiscence; 7died pWllW ?uscI~; ‘COrOflary afiery embolus; ’ Centrd line InfectIOn; “culture not obtained; diagnosis Of endacarditis unsuspected; 12pneumonia; %ecropsy 5 years after replacement of infected bioprosthesis; 14rexivd for Operabon was persistent bacteremia despite antibiotics; %entral line placement; “dental abscesses,; 18Ldffler’s fibmblastic parietal endocarditis; %ellulitis 1 month before death; ~Opercutaneous liver biopsy; “patient extended Into the sewing ring of the bioprosthesis in the aortic position; 23this fatal episode of endocardibs was preceded by 2 episodes of endwarrjitis 12 arA1” L-t -1 lll”111113dlle, ---IL-y-- ..-a.,= rr.nlaPLment “dl”L ._r .___..._.... A = aOrtlC; AS = aortlc stenosis; B = bovine; BPE = bioprosthetic endocarditis; 8PV = biopmsthetic valve; Ca* = calcium; CE = Carpentier-Edwards; (3HD = complete heart block; CHF = congestive heart fai!ure;_f ~~~~~~ .,~ ~~~~. ^ habitual alcoholism; H’+’ = beart weight; IE = infective endocarditis: IVDA = intravenous drug abuse; LV = left ventricular; M = male; Mi = mitral; MS = mitral stenosis; N = necropsy; IY~ = necrosis; r = po~~ne; > systemic emboli; T = tncuspld; VR = valve replacement.
I
63
NO.
2
Age (years) at VR/or BPE or @Death
TABLE I Clinical and Morphologic Features of Patients with Infective Endocarditis lnvolvina a Bioprosthetic Valve
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signs and symptoms of bioprosthetic endocarditis was %O days (range 3 to 120 months, mean 36) (late infection); the interval from the first valve replacementto the replacementof a bioprosthesis (n = 12) ranged from 27 to 144 months (mean 73), and that from the tirst valve replacement to death (n = 17) ranged from 3 to 110 months (mean 28). Two of the 12 patients who had operative excision of an infected bioprosthesis subsequently died, and an autopsy was performed; patient 22 (Table I) died 5 years after successfulexcision of the infected bioprosthesis,and patient 32 (Table I) died 1 day after operative excision of the infected bioprosthesis.
The 29 patients in whom Y bioprosthesis became infected late also were subdivided into 3 groups: 1 group consisted of 16 patients with isolated aortic valve replacementwith a bioprosthesis; 1 consistedof 6 patients with isolated mitral valve replacement,and 1 consisted of 7 patients in whom 22 cardiac valves were replaced. Of the 29 patients with infection late, 24 had evidence of active IE involving 22 bioprostbesis, and the active nature of the bioprosthetic endocarditis was confirmed by morphologic study of the operatively excised bioprosthesisor from necropsy study of the bioprosthesis. The other 5 patients (nos. 7, 16, 23, 24 and 28; Table
FmlJREAPatkmt9.Alphar5reptococcur~ valveendoc&itkina75year.oldmm(QT#828’1999).~~ thesIswasexcised94monMsafteraottkvalve re(?acement.llw3patientrewivednealiy7weekrof allubwwwthe wumdvalve repkmwt.4aelticwpectefthe~valve.4venbicula~efthebiopostheticvalve, ahew~whdwtauwwd~efnlecusp.c,caspshavebewremewd fremtheatentwdlaidfiat,bettershew iq(theI-wll~.
318
THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
AUGUST1,1993
BIOSPROSTHETIC ENDOCARDITIS 319
I) had unequivocal clinical evidence of active infection involving a bioprosthesis,but operative excision of the involved bioprosthesis was not performed until 6 to 48 months (mean 27) after the onset of signs or symptoms, or both, of active bioprosthetic endocarditis. Examination of the operatively excised bioprostbesesin 2 of the 5 patients (nos. 24 and 28) disclosed perforations in 2
320
THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
of the 3 bioprosthetic cusps, a finding typical of healed IE4; each of the other 3 patients had parabasilar leaks, with parabasilar aneurysm, from disruption of the bioprosthetic ring from the native valve a~ulus due to the infection, which had healed.The pamannularaneurysms are indicative of previous IE.5 None of the 5 patients at any time had evidence of active lE of a native cardiac
AUGUST1,1993
BIOSPROSTHETIC ENDOCARDITIS 321
FlwREl3.Patknt33.
12. Of these 12 patients, 7 are alive and well at present (New York Heart Association functional classesI and II) 5 to 10 years (mean 7) after excision of the infected bioprosthesis.In these 7 patients, the infective material was located on the cusp only in 2, and on both the cusp and ring in 5. One of the latter 5 patients had a parabasilar leak. The remaining 5 patients are dead. One patient died ~24 hours after reoperation for active bioprosthetic endocarditis, including an abscessat the junction of the aorta and left atrium. The other 4 patients had operative excision of the infected bioprosthesis (n = 3) or after healing of the bioprosthetic infection (n = 1); 1 died from a noncardiac cause (cancer of the lung) 1.5years after reoperation, 1, an opiate addict, died from active bioprosthetic endocarditis 3 years after the first infective bioprosthesis was excised, 1 died shortly after pericardiectomyfor constriction 5 years after excision of the infected bioprosthesis, and 1 died of pneumonia 14 years after excision of the infected bioprosthesis.The latter patient had a parabasilar bioprosthetic communication.
tN4@amaswfeus~etk
endacditk in a 67-yakoholk num (DCGH# 85Ad8) whohdundw@neaertkadmltralvalvereplacement8 months~death.Hk~rstsynlptomwasanacuteante darnwocdklinfarctknfroma -rrtMye-s. Hedkdthatdayaftardevekphgcompkte~bkck. Shownherekaviewdthe4baseofthehsartafbrmmoval efthekft(LA)mldliglt(RA)ablumrAppre~so% afulecircumfemnce ottheSWhlgrilbgOfdbi~8 hlthemitralpesitknkinvolvedbytk3ling-TheA b8WSCOlMhgOfthSS8Willgfl~iSdenuded,~XpOSillgC
cloUwoveredsewiJrin&Portknsofthe~in theaertkposltkn(AV)wevidbk.P7=pulmemmyt~nk.
valve (i.e., at the time of operation and replacementwith a bioprosthesis). LocatbnafthehfecUonhthehtehfecHon#oup:
Of the 22 patients with isolated aortic valve (n = 16) or mitral (n = 6) replacement, the infection involved the valvular cuspsonly in 8 (36%), the ring only in 6 (27%), and both the cusps and ring in 8 (36%). Thus, the bioprosthetic ring was involved in 14 patients (64%) and the cusps only in 8 (36%). Of the 7 patients with multiple valve replacement,a total of 15 valves were replaced with bioprostheses:of the 7 bioprosthesesin the mitral position, all were infected (cusps only in 5, and cusps and ring in 2); of the 3 bioprosthesesin the aortic valve position, 1 was infected (cusps and ring); of the 5 bioprosthesesin the tricuspid valve position, 2 were infected (cusps only). Thus, of the 29 patients with late infection, a total of 37 valves were replaced with bioprostheses:of the 19 bioprosthesesin the aortic valve position, 17 were infected (cusps only in 6, ring only in 4, and both in 7); of the 13 bioprosthesesin the mitral position, all were infected (cusps only in 7, ring only in 1, and both in 5); of the 5 bioprosthesesin the tricuspid valve position, 2 were infected (cuspsonly). Thus, in the 29 patients with late infection, 37 bioprostheseswere inserted: 32 were infected (cusps only in 15 [47%], ring only in 5 [16%], and both in 12 [37%]) and 5 were not. Of the latter 5 bioprostheses,3 had been in the tricuspid valve position and 2 in the aortic valve position. Of the 13 patients in whom the infected bioprosthesis was excised, follow-up information was available in 322
THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
DISCUSSION In this study, the location of the infective material was sought in the 13 patients who had operative excision of a presently (n = 9) or previously (n = 4) infected valvular bioprosthesis and in the 21 who were studied at necropsy with a presently (n = 20) or previously (n = 1) infected valvular bioprosthesis.Five of the total 34 patients (15%) developed clinical evidence of active IE within 60 days of replacement of a native cardiac valve with a bioprosthesis, and 29 patients (85%) developed evidence of bioprosthetic endocarditis at later periods. Of the 43 bioprosthesesin the 34 patients, 37 were sites of infection: the infection involved the bioprosthetic cusps only in 17 (46%), the sewing ring only in 8 (21%), and both the cusps and sewing ring in 12 (33%). No significant differenceswere noted in the location of infection basedon the specific organism causing infection. Of the 13 patients having operative excision, 9 had active infection at the time, and operative survival and outcome were similar in the 4 in whom the infection was limited to the cusps and in the 5 in whom the sewing ring was involved with (n = 2) or without (n = 3) involvement of the valve cups. Although a number of previous publications described infection of a bioprosthesis,“‘* we found only 2 reports that provided data on individual patients with an infected bioprosthesis.%11The study by Bortolotti et al* included 9 patients (10 bioprostheses), and that by NGiez et allo included 13 patients (16 bioprostheses) with presently or previously infected bioprosthetic valves: 9 developedinfection early (~60 days) and 13 at later periods. Of the 30 bioprosthesesin the 22 patients, 24 were sitesof infection: the infection involved the bioprosthetic cusps only in 16 (66%), the sewing ring only in 2 (8%), and both in 4 (16%). It is unclear why so few of our 34 patients had the bioprosthetic infection limited to the bioprosthetic cusps and why so many of the previously reported caseshad the infection limited to the cusps. In contrast to our study, however, where only 1
AUGUST1.1993
of 13 patients having operative excision of the bioprosthesis died early (40 days), 27 of the 22 previously reported patients having operative excision of the bioprosthesisdied early. Acknowledgment: We wish to thank Vivian Norman and Linda Raley for assistancewith manuscript preparation, and Michael Spencer for photography of gross specimens. 1. Cohn LH, Roberts WC, Rockoff SD, Morrow AG. Bacterial endocarditis following aortic valve replacement. Clinical and pathologic con&tions. Circulation 1966;33:209-217. 2. Amen EN, Roberts WC. Prosthetic valve endocarditis: clinicopathologic analysis of 22 necropsy patients with comparison of observations in 74 necmpsy patients with active infective endocarditis involving natural left-sided cardiac valves. Am J Cardiol 1976;38:281-292. 3. Am&t EN, Robxts WC. Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 9.5 necropsy patients. Circulation 197654: 140-145.
4. Buchbinder NA, Roberts WC. Healed left-sided infection: a clinicopatbologic study of 59 patients. Am J Cardiol 1977;40:876-888. 5. McManus BM, Katz NM, Blackboume BD, Gottdiener JS, Wallace RB, Roberts WC. Acquired cm triahiahun (left ventricular false aneurysm): complication of active infective endocarditis of the amtic valve with ring abscess treated by valve replacement. Am Heart J 1982;101:312-314. 6. Magilligan DJ, Quinn EL, Davila JC. Bacteremia, endocaditis, and the Hancock valve. Ann Thorac SWg 1977;24:508-519. 7. Fenans VJ, Boyce SW, Billingham ME, Spray TL, Roberts WC. Infection of glutarakiehyde-preserved pm&e valve hetaogmfts. Am J Cardiol 1979;43: 1123-1136. 8. Bmtolotti U, Thiene G, Milano A, Pan&on G, Vale& M, Gallucci V. Pathological study of infective endocxditis on Hancock porcine bioprosthesis. J Thorac Cardiovasc Surg 198 1;s 1:9%942. 9. Amett EN, Roberts WC. Pathology of active infective endocarditis: a necmpsy analysis of 192 patients. Thorac Cardiovasc Sq 1982;30:327-335. 10. N&z L, de la Llana R, Aguado GM, Iglesias A, Larrea JL, Celemin D. Bioprosthetic valve endocarditis: indicators for surgical intervention. Ann Thorac Surg 1983;35:262-270. 11. Glazier JJ, Verwilghen J, Donaldson RM, Ross DN. Treatment of complicated prosthetic aatic valve endocarditis with anular abscess formation by homogra!i aortic root replacement. J Am CoN Cardiol 1991;71:1177-1182. 13. Gaglianii C, Di Tommaso L, Mastrorobato P, Stawno P, Spampinato N. Bicprosthetic valve endccaditis: factors affecting bad outcome. J Cardiovasc Surg 1991;32:8Of1X6.
BIOSPROSTHETIC ENDOCARDITIS 323