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Prosthetic valve endocarditis
SEPTEMBER
American
The
Journal
1976
of CARDIOLOGY” VOLUME NUMBER
CLlNlCAL
38 3
STUDlES
Prosthetic Valve Endocarditis Clinicopathologic Analysis of 22 Necropsy Patients With Comparison of Observations in 74 Necropsy Patients With Active Infective Endocarditis involving Natural Left-Sided Cardiac Valves ERNEST
N. ARNETT,
WILLIAM
C. ROBERTS,
MD MD,
FACC
Bethesda, Maryland
From the Pathology Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, Md. Manuscript received January 16, 1976; revised manuscript received March 29, 1976, accepted March 31, 1976. Address for reprints: William C. Roberts, MD, Bldg. lOA, Room 3E-30, Nationalinstitutesof Health, Bethesda, Md. 20014.
Clinical and morphologic features are described in 22 necropsy patients with endocarditis involving rigid-framed prosthetic valves: aortic in 15 patients and mitral in 7. The interval from valve replacement to onset of symptoms of prosthetic valve endocarditis was less than 2 months in 8 patients and longer than 2 months in 14 patients. The most frequent infecting organism was the Staphylococcus (13 patients). In each of the 22 patients the infection was located behlnd the site of attachment of the prosthesis to the valve ring, and the infection spread to adjacent structures in 13 patients, Ii of whom had aortic prostheses. Prosthetic detachment causing severe r~urg~ation occurred In 12 ot the 15 patients with an infected aortiC valve prosthesis, and in 2 of the 7 with an infected mitral valve prosthesis. Prosthetic obstruction by vegetative material occurred in 5 of 7 patients with prosthetic mitral infection and in only 1 of 15 with prosthetic aortic infection. High degrees of conduction defects developed in seven patients with aortic prosthetic valve endocarditis: complete heart block in five, and complete left bundle branch block In two. Comparison of observations in the 22 patients with prosthetic valve endocarditis with those in 74 patients with active infective endocarditis involving natural left-sided cardiac valves revealed significant (P <0.05) differences in the percent with ring abscess, hemodynamlc consequences of the endocarditis (valve stenosis), frequency of Staphylococcus as the causative organism and percent with complete heart block or left bundle branch block. No significant differences were observed between the two groups when comparing age, sex, type of underlying valve disease or frequency of organ infarcts or splenomegaly.
Among 450 consecutive patients with one or more rigid-framed prosthetic cardiac valves studied by us at necropsy,1-7 22 (5 percent) had infection involving a prosthetic valve. These 22 patients represent 17 percent of the 127 patients with active valvular infective endocarditis studied in this laboratory.s-10 Although many reports are available on patients with fatal active infective end~ditis involving natural cardiac valves, surprisingly little information is available on the morphologic
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
AND ROBERTS
features of endocarditis involving prosthetic cardiac valves. This report consequently focuses on the clinicopathologic features in 22 patients with prosthetic valve endocarditis and compares them with the features we observed in 74 nonsurgical necropsy patients with active infective endocarditis involving natural left-sided cardiac valves.
TABLE Prosthetic
Valve
Endocarditis: Aortic Valve
Caged ball Tilting disc Poppet disc Totals
Patients Studied Clinical observations: Clinical and morphologic observations in the 22 patients with prosthetic valve
I
l
Starr-Edwards;
Type of Prosthesis Infected Mitral Valve
l$ 15
6’ 0 l§ 7
+ Bj&k-Shiley;
$ Hufnagel;
;;
TOMIS
15” 5+ 2; 8 Kay-Shiley.
FIGURE 1. Staphylococcus epidermidis prosthetic valve endocarditis in a 49 year old man who died 3 months after aortic valve replacement Symptoms of infection appeared 16 days before death. Despite large doses of antibiotic agents, complete heart block and severe aortic regurgitation developed. a, opened aorta, aortic valve and left ventricle (L.V.) showing a necrotic anulus to which the prosthesis is only partially attached. A. = anterior mitral leaflet. b, opened right atrium, tricuspid valve and right ventricle (R.V.) showing vegetative material (arrows) that had burrowed through the atrial septum from the necrotic aortic valve ring. C.S. = ostium of coronary sinus: S.T.L. = septal tricuspid leaflet; A. = anterior tricuspid leaflet. c, longitudinal section of the heart with the anterior portion removed. The necrotic aortic valve (A.V.) ring is again seen and the penetration of the infective process through the atrial septum (A.S.) is apparent. An arrow indicates the vegetation in the right atrium @.A.). V.S. = ventricular septum. d and 8, histologic sections through the ring abscess. The site of attachment (Attach.) of the prosthesis, which has been removed, is indicated. The infected nodule, an extension of the ring abscess (Abs.), is showing in the right atrium. Ao. = aortic wall: L.A. = left atrium; A.M.L. = anterior mitral leaflet.
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
AND ROBERT’S
TABLE II Prosthetic Endocarditis: Clinical Observations in 22 Cases
Preop Lesion Patients
Prosthesis Infected Aortic Mitral Totals
no. 15 2:
CHB = complete
PA
F
37-69 37-65 37-69
13 3 16
2
heart block;
Stenosis
Pure Regurgitation
<2 mo
>2 mo
12 7 19
: 3
3” 8
10 4 14
Sex
Age Range and Average (yr) (54) (52) (53) LBB5
6”
Duration of Signs and Symptoms of infection ~ x0 <60 Days Days
interval From Valve Replacement to infection
Patients Receiving Antibiotjcs >7 Days (no.1
LBBB
9 2 13
; 2
5
10
:
lt5
Prosthetic Dysfunction Conduction Disturbance CHB
Regurgitation
Stenosis
z 5
11 0 11
A. 1
= I&t bundle branch block; Preop = preoperative.
endocarditis are summarized in Tables I to V, and some of the morphologic features are illustrated in Figures 1 to 11. Certain observations in severaIof these patients Patients with active have appeared elsewhere.1-3,11-13 infective endocarditis at the time of valve replacement were excluded, The 22 patients had 27 prosthetic cardiac valves; 17 patients had one prosthetic valve and 5 had two prosthetic valves. Of the 27 prosthetic valves, 22 were infected (Table I): the aortic prosthesis in 15 patients and the mitral in 7. Clinical evidence of infective endocarditis was present less than 2 months after operation in 8 patients (early deaths) (Table II), and from 3 months to 10 years after valve replacement in 14 patients. In 6 of the latter 14 patients clinical evidence of infection did not appear until more than 1 year after valve replacement. The duration of signs and symptoms of infective endocarditis ranged from 14 days to 13 months. In 16 patients, the duration of illness was less than 60 days and, in 6 patients, more than 60 days. Factors predisposing to development of endocarditis were apparent in only 5 of the 14 patients who died late: tooth extraction (2 patients), skin graft infection (1
TABLE III Prosthetic Valve Endocarditis: Infecting Organism
patient), prolonged use of an intravenous catheter (1 patient) and prolonged use of a transthoracic pacing wire (1 patient). It is presumed that the infection in the eight patients who died early either was incurred at operation or was secondary to a wound infection. The infecting organisms (cultured from the blood during life in 20 patients) are listed in Table III. Staphylococcus was the responsible organism in 13 patients, and a different organism in each of the other 9. Fungi caused the endocarditis in two patients who had negative blood cultures during life. Evidence of prosthetic dysfunction was present clinicallyin 12 of the 15 patients with an infected aortic valve prosthesis
TABLE IV Prosthetic Valve Endocarditis: Necropsy Observations in 22 Cases
Prosthesis Infected
Patients (no.)
Ring Abscess
Aortic Mitral Totals
15 21
15 23
Ring Organisms : 13
Prosthetic Valve Detachment (Regurgitation)
Prosthetic Valve Stenosis
12 2 14
1 ;
Onset From Valve Replacement Organism I. Gram-positive bacterium Staphylococcus epidermidis Staphylococcus aureus Streptococcus pneumoniae Group-D streptococcus Diphtheroids Listeria monocytogenes Ii. Gram-negative bacterium Proteus mirabilis Klebsietla species Serratia marcescens Ill. Fungus Candida species Aspergillus fumigatus Totals
>2 mo
<2 mo 6 3 :,
11 7 1 1
01 0 1
1 1 2
0 1 1
:: 1 0 1
3
Prosthetic Valve Endocarditis: Organ Weights and infarcts in 22 Cases
Prosthesis infected
Patients (no.)
Organ Weight (g) (range and average) Spleen
Liver
Gross Infarcts (no. of patients) Kidney
Brain
7
3
3
5
4
4
12
7
7
Spleen
1 Aortic
15
Mitral
7
1 1
:, 8
17 IO 3 1
: I 1
TABLE V
Totals
2 1 1
14
Totals 22
September 1976
The
22
120- 1000 (470) 176-920 (370) 120- 1000 (460)
1450-2950 f2140) 1350-2000 (1755) 1350-2950 (2050)
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
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(regurgitation in 11 and stenosis plus regurgitation in l), but in none of the 7 patients with an infected mitral valve prosthesis. High grade conduction disturbances occurred in 7 patients, all in the group of 15 with an infected aortic prosthesis: left bundle branch block in 2 and complete heart block in 5. Thirteen of the 22 patients received appropriate antibiotic therapy for more than 7 days. Three patients underwent valve replacement for prosthetic endocarditis. The principal causes of death in the 22 patients were congestive heart failure (19 patients), central nervous system embolus (2 patients) and generalized infection (1 patient). Morphologic observations: Among the 22 patients, 17 had one valve prosthesis and 5 had two valve prostheses. In each of the five latter patients, only the
“downstream” prosthesis was infected: the aortic prosthesis in the three patients with mitral and aortic prostheses, and the mitral prosthesis in the two patients with tricuspid and mitral prostheses. Twelve of the 15 infected aortic valve prostheses and 2 of the 7 infected mitral valve prostheses were partially or completely detached. In contrast, 5 of the 7 infected mitral prostheses and only 1 of the 15 infected aortic prostheses were obstructed by vegetative material. Ring abscesses (Table IV) were present in each of the 22 infected prostheses; in one the abscess was visible only by histologic examination. The ring abscess involved the entire valve anulus in 14 patients and only portions of the anulus in the other 8. In 13 of the 22 patients the infective process spread to adjacent
FIGURE 2. Staphylococcus epidermidis prosthetic aortic valve endocarditis in a 48 year old man. He had been well for 11 months after insertion of the Starr-Edwards prosthesis when, 1 month before death and 6 weeks after dental extraction, shaking chills appeared and blood cultures were positive for Staphylococcus epidermidis. Despite intensive antibiotic therapy, signs of aortic regurgitation appeared, and minutes before death he complained of “feeling funny.” a, chest roentgenogram immediately after death revealed that the prosthesis had dislodged and migrated to the aortic arch. b, anterior view of the heart and opened ascending aorta. The detached prosthesis ball is visible, lodged in the transverse aorta. L.V. = left ventricle; R.V. = right ventricle. c, opened aorta, aortic valve “ring” and left ventricle showing a totally necrotic aortic anulus. L.C. = ostium of left coronary artery; M.V. = anterior mitral leaflet; R.C. = ostium of right coronary artery. d, opened right atrium (R.A.), tricuspid valve and right ventricle showing a ring abscess (dashed circle) that had extended from the prosthetic aortic valve anulus. e, photomicrograph through the aortic valve “ring” showing a large ring abscess and the necrotic aortic anulus material that extended through the membranous ventricular septum into the right atrium. T.V. = tricuspid valve leaflet; V.S. = ventricular septum. (Hematoxylin-eosin X2, reduced by 24 percent.)
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PROSTHETIC VALVE
structures. In 11 of the 15 patients with an infected aortic aortic valve prosthesis the ring abscess burrowed into adjacent structures: through the ascending aorta into the periaortic space (7 patients); through the atrial septum into the right atrium (9 patients) or into the left atrium (2 patients); through the ventricular septum into the right ventricle (8 patients); and into the anterobasal left ventricular wall (2 patients). In two patients with an infected mitral valve prosthesis the ring abscess burrowed through the atria1 wall into the pericardial space. Histologic examination of the infected rings
ENDOCARDITIS-ARNETT
AND ROBERTS
disclosed colonies of organisms in 13 of the 22 patients. Both arterial emboli and gross organ infarcts were common with both prosthetic aortic and prosthetic mitral valve endocarditis (Table V). Grossly visible infarcts were present in the spleen in 12, the kidney in 7 and the brain in 7 of the 22 patients. Two patients had a bowel infarct, one a pancreatic infarct and one a transmural myocardial infarct. In addition, mycotic aneurysms were present in the ascending aorta of three patients: in two patients, aneurysms resulted from jet lesions from the infected prosthesis and, in the third, the cage of the partially detached prosthesis burrowed into the wall of a weakened aorta (after an aortotomy performed weeks earlier) causing a sacular aneurysm. The spleen ranged in weight from 120 to 1,000 g (average 460) and in 14 of the 22 patients it weighed more than 300 g. The liver ranged in weight from 1,350 to 2,950 g (average 2,050). Comments Clinical Features Incidence: Study of our 22 necropsy patients and analysis of more than 150 necropsy cases of prosthetic valve endocarditis reported by otherslM7 allows certain general conclusions regarding this condition. It is a devastating complication of cardiac valve replacement,
FIGURE 3. Staphylococcus epkfermidis prosthetic aortic valve endocarditis in a 55 year old man. The Starr-Edwards prosthesis was used to replace an infected trileaflet Teflon@ @fuller) valve 45 days before death. a, electrocardiogram revealing complete heart block and signs of massive aortic regurgitation that appeared despite antibiotic therapy. b, opened aorta, aortic valve and left ventricle. The aortic valve ring is necrotic, and the prosthesis is almost totally detached. The cage of the prosthesis has burrowed into the wall of the aorta causing a saccular aneurysm (An.). M.V. = mitral valve. c, longitudinal section showing the caged ball prosthesis burrowing into the ascending (Asc.) aorta, producing the aneurysm. R.A. = right atrium: T.V. = septal tricuspid valve leaflet; V.S. = ventricular septum. d, photomicrograph through the same area after removal of the prosthesis. (Hematoxylin-eosin X2, reduced by 25 percent.)
FIGURE 4. Staphylococcus epidermidis prosthetic aortic valve endocarditis in a 51 year old man. The stenotic bicuspid aortic valve had been replaced with a Bjork-Shiley prosthesis 83 days before death. Fever was present in the early postoperative period, and shortly before death complete heart block and signs of congestive heart failure appeared. a, longitudinal section of the heart with the anterior portion removed. The Bjork-Shiley (B-S) prosthesis is partially detached and the ring abscess (arrow) has burrowed through the ventricular septum (VS) into the right ventricle (RV). LA = left atrium; LV = left ventricle. b, rhythm strip obtained shortly before death revealing complete heart block.
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PROSTHETIC VALVE ENDOCARDITIS-ARNEll
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but fortunately it is infrequent. The exact incidence rate is uncertain but it is clearly less than 1 percent annually among patients with prosthetic cardiac va1ves.37~39~45~48 Although prospective studies49*50 have been inconclusive, retrospective studies 16~7~~~5~have shown a reduction in the frequency of early (less than 2 months
after valve replacement) endocarditis coincident with the use of prophylactic antibiotic therapy. Late prosthetic valve infection now appears to be more common than early infection,37v45 presumably because there are now so many persons with prosthetic cardiac valves. Although the mortality rate is high for both groups,
FIGURE 5. Serratia marcescens prosthetic aortic valve endocarditis in a 57 year old man whose infection occurred 4 months after replacement of both aottic and mitral valves. The apparent source of the infection was an intravenous catheter. Left bundle branch block and signs of aortic regurgitation appeared and, despite massive doses of antibiotic agents, he died 3 months after the onset of symptoms of infection. a, view of the aortic prosthesis from above. Infected thrombus is present on its anulus. b, view of the prosthesis as it appeared from the left ventricle. Some of the infected thrombus became detached during excision of this prosthesis at necropsy. The primary orifice is partially obstructed by the infected material. c, opened aortic root, aortic valve and left ventricle (LV) after removal of the aortic prosthesis. Most of the aortic ring is necrotic. In addition, the portion of mitral (M) prosthesis in direct apposition to the aortic anulus also is infected. d, view after excision of the mitral prosthesis showing extension of the aortic anutar infection into the junctional area between the aortic and mitral anuli. LA = left atrium.
FIGURE 6. Staphylococcus epidermidis endocarditis originally involving a Bjork-Shiley aortic valve prosthesis that was excised and replaced with a Magovern prosthesis 28 days before death in a 69 year old man. Fever and signs of aortic regurgitation appeared 7 months after aortic Valve replacement with the Bjork-Shiley prosthesis. After replacement with the t&govern prosthesis, a murmur of aortic regurgitation reappeared. At necropsy, the sewing ring of the Magovern prosthesis had burrowed deeply into the necrotic anulus, causing the ball of the prosthesis to strike the nonnecrotic portion of the aortic wall, probably producing prosthetic aortic stenosis. a, longitudinalsection of the heart through the aortic anulus with the Magovern Drosthesis in Dlace: b. section after removal of the Drosthesis. The frame of the prosthesis has burrowed deeply into the necrotic anUtUS. LA = ieft atrium: LV = left ventricle; MV = mitral valve; dV = right ventricular cavity; i/S = ventricular septum.
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early prosthetic valve infection apparently is more often fatal than late infection.37Jsp45**s Etiology: Most early infections either are incurred at operation or result from a wound infection.25~2g~37~3g~48 Those at operation appear to result from contamination of the cardiopulmonary bypass equipment.53p54 Staphylococcus is the organism cultured most frequently from cardiopulmonary bypass equipment and it is the most frequent cause of early prosthetic valve endoc~ditis.l*,16-1s,25,30~37,39,*4,*5 When gram-negative bacteria or fungi cause endocarditis early, they are usually also recovered from the operating room equipment or from a wound infection.28,3g Late infections usually result from transient bacteremias.37,3g~45~48 Although both staphylococci and streptococci are frequent causes of clinically diagnosed late prosthetic valve endocarditis,37,3g,45 the former have caused most cases of necropsy-proved late endocarditis and the latter relatively few. In none of our 22 necropsy patients was the
AND ROBERTS
infection caused by Streptococcus. Staphylococcus was the most common cause of endocarditis in our patients whether the infection occurred early or late. Blood cultures: Among patients with prosthetic valve endocarditis, blood cultures are almost always positive, except when the infections are caused by certain fungi.27,28,31,32,37,3g,44,45,48Blood cultures were positive during life in each of our 20 patients with endocarditis caused by bacteria and were negative in each of our 2 patients with fungal endocarditis. Blood cultures were positive in only 3 of 39 patients with endocarditis caused by Aspergillus species in a series reviewed by Kammer and Utz.55 Prosthetic valve dysfunction: Signs of prosthetic valve dysfunction are usually present when the aortic prosthesis is infected and usually absent when the mitral prosthesis is infected. Clinical signs of aortic regurgitation were present in 11 of our 15 patients with an infected aortic valve prosthesis. In three of the four
FIGURE 7. Staphylococcus aureus prosthetic mitral valve endocarditis in a 47 year old man who had the onset of symptoms of infective endocarditis 4 months after valve replacement. He had done well during the first 3 months after operation, but symptoms of infection developed after grafting of a cutaneous ulcer. Signs of prosthetic dysfunction were never detected clinically. a, prosthetic mitral valve orifice obstructed by vegetative material, as viewed from the left atrium. b, opened left atrium, mitral anulus and left ventricle after removal of the mitral prosthesis. The entire anulus is necrotic. AV = aortic valve. c, mitral valve prosthesis showing infected thrombus at its base. d, longitudinal section through the left atrium (LA), mitral anulus and left ventricle (LV). The former site of attachment of the prosthesis is designated by the dashed lines. The infective process burrowed through the wall of the heart and caused pericarditis. CA = coronary artery; CV = coronary vein in the right atrioventricular sulcus. e and 1, hematoxylin-eosin-stained histologic sections of the left ventricle remote from the infected mitral anulus. 8, infected embolus in an intramural coronary artery. f, microscopic-sized myocardial abscess. (X400 [e] and X 160 [f], reduced by 24 percent.)
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
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patients without clinical signs of aortic regurgitation, the prosthesis was not detached at necropsy. Among patients with acute aortic regurgitation, however, classic signs of aortic regurgitation may be absent.s6-5g Signs of aortic regurgitation were not detected in three of nine necropsy patients with prosthetic aortic valve endocarditis described by Madison et a1.,44but all three had prosthetic detachment at necropsy. In contrast, patients with infection involving the mitral valve prosthesis usually have no clinical signs of prosthetic mitral valve dysfunction. Clinical signs of such dysfunction were not detected in any of our seven patients with prosthetic mitral valve endocarditis although the prosthesis was significantly obstructed by vegetative material in five of the seven and partially detached from the anulus in two.i2 McAllister et a1.43 reported on two patients with virtual total obstruction of the mitral prosthesis. Morphologic Features Valve ring abscess: The most consistent morphologic feature of prosthetic valve infection in our 22 pa-
tients was infection behind the site of attachment of the valve prosthesis, resulting in valve ring abscess. Ring abscess was present in each of our 22 patients, and in 14 the infection involved the entire circumference of the valve anulus. In several patients, however, only a portion of the circumference of the valve anulus was involved and, in one patient, histologic examination of the anulus disclosed infection that had not been apparent on gross examination. Extension of the ring infection to adjacent cardiac structures was common, especially when the aortic prosthesis was infected. This extension resulted in the frequent occurrence of both intracardiac fistulas and complete heart block or left bundle branch block. Among nine necropsy patients with prosthetic aortic valve endocarditis described by Madison et a1.,44each had infection at the site of attachment of the prosthesis, and atrioventricular conduction defects developed in 7 (44 percent) of their entire group of 16 patients with prosthetic aortic valve endocarditis. Obviously, it is the occurrence of the infection behind the site of attachment of the prosthesis that makes reoperation so hazardous. Were the infection limited to the interior por-
FIGURE 8. Staphylococcus epidermidis prosthetic mitral valve endocarditis in a 46 year old man who died 16 months after mitral valve replacement with a Starr-Edwards prosthesis. Eight months postoperatively, when he was asymptomatic, cardiac catheterization disclosed normal left atrial pressure and cardiac output. Signs of infection appeared 15 months after valve replacement. Despite antibiotic therapy, fatal congestive heart failure developed. a, mitral valve prosthesis as viewed from the left atrium. A large infected thrombus virtually occludes the mitral valve orifice. b, opened aorta, aortic valve (AV) and left ventricle (LV) showing infected thrombus on the cage of the mitral prosthesis. c, opened left atrium and ventricle showing a completely necrotic mitral valve anulus. The prosthesis has been removed.
FIGURE 9. Staphylococcus epidermidis prosthetic mitral valve endocarditis in a 59 year old woman. The infection appeared IO years after replacement of both mitral and tricuspid valves. At necropsy, only the mitral prosthesis was infected. a, infected mitral valve prosthesis viewed from the left ventricle. Vegetative material (V) is present on the prosthetic anulus just below the aortic valve. b, prosthesis as viewed from the left atrium showing vegetations(V) at the junction of the prosthetic and natural valve anuli. c, same view after removal of the prosthesis showing even greater extensiveness of the infection at the site of attachment of the prosthesis.
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PROSTHETIC VALVE
tion of the prosthesis, excision of the prosthesis should eliminate the infection. Unfort~a~ly, as demonstra~d in our patients and in those described by others,20*35*38,43*44,47 the tissues behind the site of attachment of the prosthesis usually are involved by the infective process. Treatment Replacement of infected prosthesis: The occurrence of a grossly necrotic anulus at the time of reoperation for prosthetic valve endocarditis does not necessarily mean that valve replacement will be fruitless. Although it may be grossly necrotic, the anulus may be free of colonies of organismsand cultures of the necrotic anulus may be negative. In 9 of our 22 patients with prosthetic valve endocarditis and ring abscess, no stainable organisms were found in histologic sections from the prosthetic anulus. One hazard of inserting a prosthesis in a necrotic anulus at the time of valve replacement for prosthetic valve endoc~ditis is b~ro~ng of the sewing ring of the new prosthesis into the necrotic anulus with resulting impingement on movement of the poppet of the prosthesis by adjacent tissue. This sequence occurred in one
ENDOCARDITIS-ARNETT
AND ROBERTS
of our patients and resulted in prosthetic aortic stenosis from inability of the ball to ascend in the cage (Fig. 6). Tissue valve endocarditis: Although prosthetic valve endocarditis in patients with rigid-framed prostheses (the kind present in our 22 patients) usually indicates infection behind the site of attachment of the prosthesis, that is, the sewing ring, ring abscess may be less frequent with endocarditis involving tissue valves. Indeed, in animals and in man, the infective process may be limited to the cusps of the tissue valve, as when infective endocarditis involves natural valves.eQ$el Thus, the chance of cure, either by antibiotic therapy or valve replacement, or both, when infective endocarditis is superimposed on a homograft or heterograft (porcine valve, for example) is much better than when endocarditis involves a rigid-framed prosthesis6i This, then, is an advantage,although a small one, of the tissue valve (porcine) over the rigid-framed prosthesis. Diagnosis: Establishment of the diagnosis of prosthetic valve endocarditis, particularly in the early postoperative period at times may be difficult, as pointed out by several investigators.48s62*63 Diagnosis in the late postoperative period, in contrast, is usually
FIGURE 10. Candida species prosthetic mitral valve endocarditis in a 37 year old woman who underwent valve replacement 125 months before death because of mitral stenosis (mean mitral gradient 7 mm Hg) and regurgitation. Her tricuspid valve was replaced with a porcine xenograft because of severe tricuspid regurgitation 66 days before death. Postoperatively, she required prolonged use of a transthoracic pacing wire, which was the apparent source of the infection. She died from central nervous system embolism. Necropsy disclosed infection of the mitral valve prosthesis. a, mitral valve prosthesis viewed from the left atrium; b, prosthesis viewed from the left ventricle. Large vegetations are present on the base and struts of the prosthesis. c and d, removed mitral valve prosthesis viewed from two different sides showing large vegetations. e, photomicrograph of Candida species in the mitral vegetations. (Methenemine silver stain X860, reduced by 23 percent.) f, photomicrograph of microabscess in the left ventricular myocardium. (Hematoxylin-eosin X80, reduced by 23 percent.)
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
AND ROBERTS
made quite readily. 48,62,63 It is worth emphasizing, however, that the combination of fever and a positive blood culture in a patientwith a prosthetic cardiac valve does not always indicate the presence of prosthetic valve infection. We recently studied a patient at necropsy who was diagnosed during life as having prosthetic mitral valve endocarditis on the basis of fever, cerebral episodes consistent with emboli, and one blood culture that grew Staphylococcus epidermidis and diphtheroids. She received antibiotic treatment during most of her 4 month postoperative period and at necropsy no endocarditis was found. A left ventricular aneurysm was present immediately caudal to the mitral anulus and a sterile thrombus was present in the aneurysm (Fig. 11). The latter was the likely source of the cerebral emboli. Antibiotic agents: There seems to be a general view that prosthetic valve endocarditis can at times be cured by antibiotic drugs. For such cure to be established, however, it is necessary that prosthetic valve endocarditis be confirmed during life, and this unequivocal confirmation can be obtained only by examination of the prosthetic valve and its anulus (site of attachment) at reoperation. In other words, to establish cure of prosthetic valve endocarditis it is necessary to be absolutely positive of the diagnosis. Although this confirmation is usually not obtained, it has now been obtained in enough patients to support the view that prosthetic valve endocarditis can indeed be cured in some patients. 16,17,21,23,24,29,30,37,39,44,45,48,64,65
FIGURE 11. Left ventricular aneurysm simulating prosthetic valve endocarditis in a 46 year old woman. She had almost daily fever after mitral valve replacement 4 months before death and one of many blood cultures grew Staphylococcus epidermidis and diphtheroids. The clinical diagnosis was prosthetic valve endocarditis and she was treated with prolonged intravenous antibiotic therapy. She died from central nervous system embolism. At necropsy, an aneurysm was present in the basal portion of the left ventricular free wall. The prosthesis and its anulus were free of signs of infection. a, longitudinal cut of the left atrial (LA.) wall, mitral anulus (A) and left ventricular (L.V.) wall through the aneurysm. b, histologic section of the aneurysm (Movat stain). Thrombus is present in the aneurysm.
TABLE
VI
Comparison
between
Active
Infective
Endocarditis
(IE)
Involving
Prosthetic
Cardiac
Valves and Natural
Mitral Valve
Aortic
Prosthetic no. Necropsy patients (no.) Age (vr) (range and average)
377-65 (52) 3:4 7
Sex ratio (male:female) Underlying valve disease Rheumatic
290
September 1976
100 -
14
4 :
57 0” 29 71 100 0 0
216
%
z
32 27
0 1+ 15 0
: 68 0
7 z
5
* Eighteen of the 52 also had infection aortic valve infection. Floppy mitral valve. Degenerative (5 patients); P <0.05.
no.
z:
endocarditis
no.
3,‘-“,9 (54) 13:2 15 -
32
14 1 1
9” 64 5 5
:, 17
: 77
3
20
that healed (3 patients)
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Volume 38
Valve Natural
%
no.
100 -
52’ 1 J-83 (45) 41:ll 26 4
-
and uncertain
%
50
:;$ 26
2: 19 50
1
7
3
6
9 0 1 12 1 15 5
60 0
13 9
25 17
366 1 21
:9’ 2 40 8
: 12
8: 7 100 33 13
:
k%
of the mitral valve, but in at least 13 of them the mitral valve infection
previous infective
Valves
Prosthetic
22 15-74 (43) 12:10
1
2 5 7 :
Spleen >300 g the + $ 0
%
-
-
Congenital Other None Previous episode I E Infecting organism Staphylococcus§ Alpha streptococcus Pneumococcus Valve regurgitation (from I E) Valve stenosis (from I E) § Valve-ring abscess5 Cqmplete heart block 0 Left bundle branch blocks Organ infarcts
Natural
Cardiac
appeared
origin (2 patients).
31147 19138 to be secondary
6: 50 to
PROSTHETIC VALVE ENDOCARDITIS-ARNETT
Comparison With Endocarditis Involving Natural Valves
Comparison of observations in our 22 patients with prosthetic valve endocarditis with our observations in 74 nonsurgically treated necropsy patients with active infective endocarditis involving natural left-sided cardiac valves disclosed certain clear differences between the two groups (Table VI): (1) Ring abscess was always present in patients with prosthetic valve endocarditis regardless of the site of the prosthesis, but was present in only 30 percent of the comparison group and then, with rare exception, only when the aortic valve was infected. (2) The hemodynamic consequences were different. Prosthetic valve endocarditis caused valve obstruction nearly as often as valve regurgitation, whereas valve stenosis from active infective endocarditis involving natural cardiac valves was extremely rare.le,@ (3) Spread of ring abscess was more extensive in patients with prosthetic valve endocarditis than in patients with natural valve endocarditis, and consequently the frequency of high grade conduction defects was much greater in the former patients. (4) The infecting organism in fatal prosthetic valve endocarditis was most commonly the Staphylococcus. Alpha streptococcus, which remains a common cause of fatal active infective endocarditis in patients with natural cardiac valves, is a rare cause of fatal prosthetic valve endocarditis. Valve xing abscess: Among patients with infective endocarditis involving native cardiac valves, ring abscess when present almost always (95 percent of cases) involves the aortic valve.67 Among our necropsy patients with active infective endocarditis involving a natural aortic valve, 40 percent had a valve ring abscess, whereas only 5 percent of patients with endocarditis involving a natural mitral valve had a ring abscess. In contrast, each of our 22 patients with prosthetic valve endocarditis had a ring abscess. Thus, valve ring abscess is the usual morphologic feature of prosthetic valve endocarditis, regardless of the valve infected. Ring abscesses in patients with infection involving prosthetic valves are generally more extensive than those in patients with active infective endocarditis involving natural cardiac valves. This appears to be a consequence of the rigid nature of the prosthetic frame.
AND ROBERTS
Once the prosthesis is loosened by the infection, the rocking-rigid frame promotes spread of the infection. The greater turbulence across the aortic valve prosthesis probably accounts for the generally more extensive nature of ring abscess with prosthetic aortic than with prosthetic mitral endocarditis. A consequence of this extension is the greater frequency of complete heart block and left bundle branch block in patients with prosthetic aortic valve endocarditis (32 percent) than in patients with natural aortic valve endocarditis (8 percent). Infecting organism: Staphylococcus (either aureus or epidermidis) is the most common cause of prosthetic valve endocarditis (59 percent). Many different organisms cause the remainder of the infections. Although alpha streptococcus was the responsible organism in 17 percent of our 74 patients with natural aortic valve infection, this bacterium was not the causative organism in any of our 22 patients with prosthetic valve endocarditis. Valve dysfunction: The hemod~~ic consequences of prosthetic valve endocarditis vary with the site of the infected prosthesis. Valve regurgitation developed in 12 of the 15 patients (80 percent) with prosthetic aortic valve endocarditis and in 2 of the 7 patients (28 percent) with prosthetic mitral valve infection. In contrast, valve obstruction developed from the infection in 5 of the 7 patients (71 percent) with prosthetic mitral valve endocarditis, and in 1 of the 15 patients (7 percent) with prosthetic aortic valve endocarditis. Among patients with natural left-sided valve infection, 65 percent (64 percent of those with mitral valve disease and 69 percent of those with aortic valve disease) had valve regurgitation from active infective endocarditis, and relatively few (3 percent) had valve obstruction from the endocarditis.lO Thus, aortic prosthetic valve endocarditis almost alv lys causes valve regurgitation and mitral prosthetic valve endocarditis most often causes valve obstruction. Splenomegaly (greater than 300 g) is common both in patients with prosthetic valve endocarditis (64 percent) and in patients with native left-sided valve endocarditis (37 percent). The frequency of infarcts in other body organs is similar in both groups (64 and 70 percent, respectively).
References Roberts WC, Morrow AG: Anatomic studies of hearts containing caged-ball prosthetic valves. John Hopkins Med J 121:271-295, 1967 Roberts WC, Morrow AO: Causes of death and other anatomic observations after cardiac valve replacement. Adv Cardiol 7: 226-247.1972 Roberts WC, BulkfeyBH, Morrow AG: Pathologic anatomy of cardiac valve replacement: a study of 224 necropsy patients. Prog Cardiovasc Dis 15539-587, 1973 Fishbeln MC, Roberts WC, Golden A, et al: Cardiac pathology after aortic valve replacement using Hufnagel trileaflet prostheses: a study of 20 necropsy patients. Am Heart J 89:443-448, 1975 - _ _ .__- -. __ _ __- _ 5. Roberts WC, Fismem MC, Go&tenA: Cardiacpathology after vatve replacement by disc prosthesis. A study of 61 nacropsy patients. Am J Cardiol35:740-760, 1975
6. Fishbein MC, Roberts WC: Late postoperative anatomic observations after insertion of Hufnagel caged-ball prosthesis in descending thoracic aorta. Chest 68:6-l 1, 1975 7. Roberts WC, Hammer WJ: Cardiac pathology after valve replacement with a titting disc prosthesis (Bark-Shiley type): a study of 46 necropsy patients and 49 Bjork-Shiley prostheses. Am J Cardiol 37:1024-1033, 1976 8. Roberts WC, Buchbinder NA: Right-sided valvular infective endocarditis. A clinicopathologic study of twelve necropsy patients, Am J Med 537-19.1972 9. Buchblnder NA, Roberts WC: Left-sided valvular active infective endocarditis. A study of forty-five necropsy patients. Am J Med 53~20-35, 1972 10. Am& EN, Roberts WC: Pathology of active infective endocarditis. A clinicopathologic study of 137 necropsy patients. Current
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Problems in Cardiology, in press. 11. Cohn LH, Roberts WC, Rockoff SD, et al: Bacterial endoGarditis following aortic valve replacement. Clinical and pathological correlations. Circulation 33:209-217, 1966 12. Roberts WC, Morrow A& Bacterial endocarditis involving prosthetic mitral valves. Clinical and pathologic observations. Arch Pathol 82:164-169, 1966 13. Arnett Ek, Roberts WC: Prosthetic valve endocarditis. A study of 18 patients at necropsy (abstr). Am J Cardiol35:120, $975 14. Bj&k VO: Aortic valve replacement. Thorax 19:369-378, 1964 15. Newman WH, Cordell AR: Aspergillus endocardiiis after open-heart surgery. Report of a case and review of literature. J Thorac Cardiovasc Surg 48:652-660, 1964 16. Amoury RA, Bowman FO Jr, Malm JR: Endocarditis associated with intracardiac prostheses. Diagnosis, management and prophylaxis. J Thorac Cardiovasc Surg 51:36-48, 1966 17. Stein PD, Harken DE, Dexter L: The nature and prevention of prosthetic valve endocarditis. Am Heart J 711393-407, 1966 18. Fraser RS, Rossall RE, Dvorkin J: Bacterial endocarditis occurring after open heart surgery. Can Med Assoc J 96: 155 1-1558, 1967 19. Lefferf AC, Hackett RL: Aspergillus aortitis following replacement of aortic valve. J Thorac &rd
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42. 43.
44. 45. 46.
47. 48. 49.
50.
5 1.
52.
53.
54.
55. 56. 57.
58.
59.
60.
61.
Starr-Edwards valve: report of a case of bacteriologic cure with antimicrobial therapy. South Med J 66: 1117- 1120, 1973 Hall WJ 3rd: Penicillium endocarditis following open heart surgery and prosthetic valve insertion. Am Heart J 87:501-506, 1974 McAllister RG, Samet J, Mazzolenl A, et al: Endocarditis on prosthetic mitral valves. Fatal obstruction to left ventricular inflow. Chest 66:682-686.1974 Madison J, Wang K, Gobel FL, et al: Prosthetic aortic valvular endocarditis. Circulation 51:940-949, 1975 Wilson WR, Jaumin PM, Danlelson GK, et al: Prosthetic valve endocarditis. Ann Intern Med 82:751-756, 1975 Rubenstein E, Noriega ER, Slmberkofl MS, et al: Fungal endocarditis: analysis of 24 cases and review of the literature. Medicine 54:331-344.1975 Robboy SJ, Kaleer J: Pathogenesis of fungal infection on heart valve prostheses. Human Pathol 6:711-715, 1975 Kloster FE: Diagnosis and ~nage~nt of compli~tions of prosthetic heart valves. Am J Cardiol 35:872-885. 1975 Conte JE, Cohen SN, Roe BB, et al: Antibiotic prophylaxis and cardiac surgery. A prospective double-blind comparison of single-dose versus multiple-dose regimens. Ann Intern Med 76: 943-949, 1972 Goodman JS, Schaffner W, Collins HA, et al: Infection after cardiovascular surgery: clinical study including examination of antimicrobial prophyl~js. N Engl J Med 287:117-123. 1968 Nelson RM, Jenson CB, Peterson CA, et al: Effective use of prophylactic antibiotics in open-heart surgery. Arch Surg 90:731-735, 1965 Herr R, Starr A, McCord CW, et al: Special problems following valve replacement. Embolus, leak, infection, red cell damage. Ann Thorac Surg 1:403-415, 1965 Ankeney JL, Parker RF: Staphylococcal endocarditis following open heart surgery related to positive indicative blood cultures. In, Prosthetic Heart Valves (Brewer LA Ill, ed). Springfield, Ill, Charles C Thomas, 1969, p 719-730 Blakemore WS, McGarrity GJ, Thurer RJ, et al: Infection by airSurgery 70: borne bacteria with cardiopulmonary bypass. 830-838, 1971 Kammer RB, Utz JP: Aspergillus species endocarditis. The new face of a not so rare disease. Am J Med 56506-521, 1974 Wigle ED, Labrosse CJ: Sudden, severe aortic insufficiency. Circulation 32:708-720, 1965 Wise JR, Bentall HH, Cleland WP, et al: Urgent aortic-valve replacement for acute aortic regurgitation due to infective endocarditis. Lancet 2:115-121, 1971 Wise JR Jr, Oakley CM, Goodwin JF: Acute aortic regurgitation in patients with infective endocarditis. The distinctive clinical features and the role of premature mitral valve closure. J Maine Med Assoc 63:273-278, 1972 Mann T, McLaurin L, Grossman W, et al: Assessing the hemodynamic severity of acute aortic regurgitation due to infective endocarditis. N Engl J Med 293:108-113, 1975 Yarbrough JW, Roberts WC, Reis RL: Structural alterations in tissue cardiac valves implanted in patients and in calves. J Thorac Cardiovasc Surg 65:364-375, 1973 Clarkson PM, Barratt-Boyes 80: Bacterial endocarditis following homooraft replacement of the aortic valve. Circulation 42:987-991, 1970-
.
62. SanUe MA, Johnson WD Jr, Hook EW, et al: Sustained bacteremia in patients with prosthetic cardiac valves. N Engl J Med 286: 1067-1070, 1972 63. Weinstein L: Infected prosthetic valves: a diagnostic and therapeutic dilemma. N Engl J Med 286:1108-l 109, 1972 64. Watanakunakorn C, Hamburger M: Staphylococcus epidermidis endocarditis complicating a Starr-Edwards prosthesis. A therapeutic dilemma. Arch Intern Med 126:1014-1018, 1970 65. Walker SR, Shumway NE, Merigan TC: Management of infected cardiac valve prostheses. JAMA 208:531-533, 1969 66. Roberts WC, Ewy GA, Glancy DL, et al: Valvular stenosis produced by active infective endocarditis. Circulation 36:449-451. 1967 67. 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 54~140-145, 1976
Volume 36
American
The
Journal
1976
of CARDIOLOGY” VOLUME NUMBER
CLlNlCAL
38 3
STUDlES
Prosthetic Valve Endocarditis Clinicopathologic Analysis of 22 Necropsy Patients With Comparison of Observations in 74 Necropsy Patients With Active Infective Endocarditis involving Natural Left-Sided Cardiac Valves ERNEST
N. ARNETT,
WILLIAM
C. ROBERTS,
MD MD,
FACC
Bethesda, Maryland
From the Pathology Branch, National Heart and Lung Institute, National Institutes of Health, Bethesda, Md. Manuscript received January 16, 1976; revised manuscript received March 29, 1976, accepted March 31, 1976. Address for reprints: William C. Roberts, MD, Bldg. lOA, Room 3E-30, Nationalinstitutesof Health, Bethesda, Md. 20014.
Clinical and morphologic features are described in 22 necropsy patients with endocarditis involving rigid-framed prosthetic valves: aortic in 15 patients and mitral in 7. The interval from valve replacement to onset of symptoms of prosthetic valve endocarditis was less than 2 months in 8 patients and longer than 2 months in 14 patients. The most frequent infecting organism was the Staphylococcus (13 patients). In each of the 22 patients the infection was located behlnd the site of attachment of the prosthesis to the valve ring, and the infection spread to adjacent structures in 13 patients, Ii of whom had aortic prostheses. Prosthetic detachment causing severe r~urg~ation occurred In 12 ot the 15 patients with an infected aortiC valve prosthesis, and in 2 of the 7 with an infected mitral valve prosthesis. Prosthetic obstruction by vegetative material occurred in 5 of 7 patients with prosthetic mitral infection and in only 1 of 15 with prosthetic aortic infection. High degrees of conduction defects developed in seven patients with aortic prosthetic valve endocarditis: complete heart block in five, and complete left bundle branch block In two. Comparison of observations in the 22 patients with prosthetic valve endocarditis with those in 74 patients with active infective endocarditis involving natural left-sided cardiac valves revealed significant (P <0.05) differences in the percent with ring abscess, hemodynamlc consequences of the endocarditis (valve stenosis), frequency of Staphylococcus as the causative organism and percent with complete heart block or left bundle branch block. No significant differences were observed between the two groups when comparing age, sex, type of underlying valve disease or frequency of organ infarcts or splenomegaly.
Among 450 consecutive patients with one or more rigid-framed prosthetic cardiac valves studied by us at necropsy,1-7 22 (5 percent) had infection involving a prosthetic valve. These 22 patients represent 17 percent of the 127 patients with active valvular infective endocarditis studied in this laboratory.s-10 Although many reports are available on patients with fatal active infective end~ditis involving natural cardiac valves, surprisingly little information is available on the morphologic
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features of endocarditis involving prosthetic cardiac valves. This report consequently focuses on the clinicopathologic features in 22 patients with prosthetic valve endocarditis and compares them with the features we observed in 74 nonsurgical necropsy patients with active infective endocarditis involving natural left-sided cardiac valves.
TABLE Prosthetic
Valve
Endocarditis: Aortic Valve
Caged ball Tilting disc Poppet disc Totals
Patients Studied Clinical observations: Clinical and morphologic observations in the 22 patients with prosthetic valve
I
l
Starr-Edwards;
Type of Prosthesis Infected Mitral Valve
l$ 15
6’ 0 l§ 7
+ Bj&k-Shiley;
$ Hufnagel;
;;
TOMIS
15” 5+ 2; 8 Kay-Shiley.
FIGURE 1. Staphylococcus epidermidis prosthetic valve endocarditis in a 49 year old man who died 3 months after aortic valve replacement Symptoms of infection appeared 16 days before death. Despite large doses of antibiotic agents, complete heart block and severe aortic regurgitation developed. a, opened aorta, aortic valve and left ventricle (L.V.) showing a necrotic anulus to which the prosthesis is only partially attached. A. = anterior mitral leaflet. b, opened right atrium, tricuspid valve and right ventricle (R.V.) showing vegetative material (arrows) that had burrowed through the atrial septum from the necrotic aortic valve ring. C.S. = ostium of coronary sinus: S.T.L. = septal tricuspid leaflet; A. = anterior tricuspid leaflet. c, longitudinal section of the heart with the anterior portion removed. The necrotic aortic valve (A.V.) ring is again seen and the penetration of the infective process through the atrial septum (A.S.) is apparent. An arrow indicates the vegetation in the right atrium @.A.). V.S. = ventricular septum. d and 8, histologic sections through the ring abscess. The site of attachment (Attach.) of the prosthesis, which has been removed, is indicated. The infected nodule, an extension of the ring abscess (Abs.), is showing in the right atrium. Ao. = aortic wall: L.A. = left atrium; A.M.L. = anterior mitral leaflet.
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TABLE II Prosthetic Endocarditis: Clinical Observations in 22 Cases
Preop Lesion Patients
Prosthesis Infected Aortic Mitral Totals
no. 15 2:
CHB = complete
PA
F
37-69 37-65 37-69
13 3 16
2
heart block;
Stenosis
Pure Regurgitation
<2 mo
>2 mo
12 7 19
: 3
3” 8
10 4 14
Sex
Age Range and Average (yr) (54) (52) (53) LBB5
6”
Duration of Signs and Symptoms of infection ~ x0 <60 Days Days
interval From Valve Replacement to infection
Patients Receiving Antibiotjcs >7 Days (no.1
LBBB
9 2 13
; 2
5
10
:
lt5
Prosthetic Dysfunction Conduction Disturbance CHB
Regurgitation
Stenosis
z 5
11 0 11
A. 1
= I&t bundle branch block; Preop = preoperative.
endocarditis are summarized in Tables I to V, and some of the morphologic features are illustrated in Figures 1 to 11. Certain observations in severaIof these patients Patients with active have appeared elsewhere.1-3,11-13 infective endocarditis at the time of valve replacement were excluded, The 22 patients had 27 prosthetic cardiac valves; 17 patients had one prosthetic valve and 5 had two prosthetic valves. Of the 27 prosthetic valves, 22 were infected (Table I): the aortic prosthesis in 15 patients and the mitral in 7. Clinical evidence of infective endocarditis was present less than 2 months after operation in 8 patients (early deaths) (Table II), and from 3 months to 10 years after valve replacement in 14 patients. In 6 of the latter 14 patients clinical evidence of infection did not appear until more than 1 year after valve replacement. The duration of signs and symptoms of infective endocarditis ranged from 14 days to 13 months. In 16 patients, the duration of illness was less than 60 days and, in 6 patients, more than 60 days. Factors predisposing to development of endocarditis were apparent in only 5 of the 14 patients who died late: tooth extraction (2 patients), skin graft infection (1
TABLE III Prosthetic Valve Endocarditis: Infecting Organism
patient), prolonged use of an intravenous catheter (1 patient) and prolonged use of a transthoracic pacing wire (1 patient). It is presumed that the infection in the eight patients who died early either was incurred at operation or was secondary to a wound infection. The infecting organisms (cultured from the blood during life in 20 patients) are listed in Table III. Staphylococcus was the responsible organism in 13 patients, and a different organism in each of the other 9. Fungi caused the endocarditis in two patients who had negative blood cultures during life. Evidence of prosthetic dysfunction was present clinicallyin 12 of the 15 patients with an infected aortic valve prosthesis
TABLE IV Prosthetic Valve Endocarditis: Necropsy Observations in 22 Cases
Prosthesis Infected
Patients (no.)
Ring Abscess
Aortic Mitral Totals
15 21
15 23
Ring Organisms : 13
Prosthetic Valve Detachment (Regurgitation)
Prosthetic Valve Stenosis
12 2 14
1 ;
Onset From Valve Replacement Organism I. Gram-positive bacterium Staphylococcus epidermidis Staphylococcus aureus Streptococcus pneumoniae Group-D streptococcus Diphtheroids Listeria monocytogenes Ii. Gram-negative bacterium Proteus mirabilis Klebsietla species Serratia marcescens Ill. Fungus Candida species Aspergillus fumigatus Totals
>2 mo
<2 mo 6 3 :,
11 7 1 1
01 0 1
1 1 2
0 1 1
:: 1 0 1
3
Prosthetic Valve Endocarditis: Organ Weights and infarcts in 22 Cases
Prosthesis infected
Patients (no.)
Organ Weight (g) (range and average) Spleen
Liver
Gross Infarcts (no. of patients) Kidney
Brain
7
3
3
5
4
4
12
7
7
Spleen
1 Aortic
15
Mitral
7
1 1
:, 8
17 IO 3 1
: I 1
TABLE V
Totals
2 1 1
14
Totals 22
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120- 1000 (470) 176-920 (370) 120- 1000 (460)
1450-2950 f2140) 1350-2000 (1755) 1350-2950 (2050)
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(regurgitation in 11 and stenosis plus regurgitation in l), but in none of the 7 patients with an infected mitral valve prosthesis. High grade conduction disturbances occurred in 7 patients, all in the group of 15 with an infected aortic prosthesis: left bundle branch block in 2 and complete heart block in 5. Thirteen of the 22 patients received appropriate antibiotic therapy for more than 7 days. Three patients underwent valve replacement for prosthetic endocarditis. The principal causes of death in the 22 patients were congestive heart failure (19 patients), central nervous system embolus (2 patients) and generalized infection (1 patient). Morphologic observations: Among the 22 patients, 17 had one valve prosthesis and 5 had two valve prostheses. In each of the five latter patients, only the
“downstream” prosthesis was infected: the aortic prosthesis in the three patients with mitral and aortic prostheses, and the mitral prosthesis in the two patients with tricuspid and mitral prostheses. Twelve of the 15 infected aortic valve prostheses and 2 of the 7 infected mitral valve prostheses were partially or completely detached. In contrast, 5 of the 7 infected mitral prostheses and only 1 of the 15 infected aortic prostheses were obstructed by vegetative material. Ring abscesses (Table IV) were present in each of the 22 infected prostheses; in one the abscess was visible only by histologic examination. The ring abscess involved the entire valve anulus in 14 patients and only portions of the anulus in the other 8. In 13 of the 22 patients the infective process spread to adjacent
FIGURE 2. Staphylococcus epidermidis prosthetic aortic valve endocarditis in a 48 year old man. He had been well for 11 months after insertion of the Starr-Edwards prosthesis when, 1 month before death and 6 weeks after dental extraction, shaking chills appeared and blood cultures were positive for Staphylococcus epidermidis. Despite intensive antibiotic therapy, signs of aortic regurgitation appeared, and minutes before death he complained of “feeling funny.” a, chest roentgenogram immediately after death revealed that the prosthesis had dislodged and migrated to the aortic arch. b, anterior view of the heart and opened ascending aorta. The detached prosthesis ball is visible, lodged in the transverse aorta. L.V. = left ventricle; R.V. = right ventricle. c, opened aorta, aortic valve “ring” and left ventricle showing a totally necrotic aortic anulus. L.C. = ostium of left coronary artery; M.V. = anterior mitral leaflet; R.C. = ostium of right coronary artery. d, opened right atrium (R.A.), tricuspid valve and right ventricle showing a ring abscess (dashed circle) that had extended from the prosthetic aortic valve anulus. e, photomicrograph through the aortic valve “ring” showing a large ring abscess and the necrotic aortic anulus material that extended through the membranous ventricular septum into the right atrium. T.V. = tricuspid valve leaflet; V.S. = ventricular septum. (Hematoxylin-eosin X2, reduced by 24 percent.)
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structures. In 11 of the 15 patients with an infected aortic aortic valve prosthesis the ring abscess burrowed into adjacent structures: through the ascending aorta into the periaortic space (7 patients); through the atrial septum into the right atrium (9 patients) or into the left atrium (2 patients); through the ventricular septum into the right ventricle (8 patients); and into the anterobasal left ventricular wall (2 patients). In two patients with an infected mitral valve prosthesis the ring abscess burrowed through the atria1 wall into the pericardial space. Histologic examination of the infected rings
ENDOCARDITIS-ARNETT
AND ROBERTS
disclosed colonies of organisms in 13 of the 22 patients. Both arterial emboli and gross organ infarcts were common with both prosthetic aortic and prosthetic mitral valve endocarditis (Table V). Grossly visible infarcts were present in the spleen in 12, the kidney in 7 and the brain in 7 of the 22 patients. Two patients had a bowel infarct, one a pancreatic infarct and one a transmural myocardial infarct. In addition, mycotic aneurysms were present in the ascending aorta of three patients: in two patients, aneurysms resulted from jet lesions from the infected prosthesis and, in the third, the cage of the partially detached prosthesis burrowed into the wall of a weakened aorta (after an aortotomy performed weeks earlier) causing a sacular aneurysm. The spleen ranged in weight from 120 to 1,000 g (average 460) and in 14 of the 22 patients it weighed more than 300 g. The liver ranged in weight from 1,350 to 2,950 g (average 2,050). Comments Clinical Features Incidence: Study of our 22 necropsy patients and analysis of more than 150 necropsy cases of prosthetic valve endocarditis reported by otherslM7 allows certain general conclusions regarding this condition. It is a devastating complication of cardiac valve replacement,
FIGURE 3. Staphylococcus epkfermidis prosthetic aortic valve endocarditis in a 55 year old man. The Starr-Edwards prosthesis was used to replace an infected trileaflet Teflon@ @fuller) valve 45 days before death. a, electrocardiogram revealing complete heart block and signs of massive aortic regurgitation that appeared despite antibiotic therapy. b, opened aorta, aortic valve and left ventricle. The aortic valve ring is necrotic, and the prosthesis is almost totally detached. The cage of the prosthesis has burrowed into the wall of the aorta causing a saccular aneurysm (An.). M.V. = mitral valve. c, longitudinal section showing the caged ball prosthesis burrowing into the ascending (Asc.) aorta, producing the aneurysm. R.A. = right atrium: T.V. = septal tricuspid valve leaflet; V.S. = ventricular septum. d, photomicrograph through the same area after removal of the prosthesis. (Hematoxylin-eosin X2, reduced by 25 percent.)
FIGURE 4. Staphylococcus epidermidis prosthetic aortic valve endocarditis in a 51 year old man. The stenotic bicuspid aortic valve had been replaced with a Bjork-Shiley prosthesis 83 days before death. Fever was present in the early postoperative period, and shortly before death complete heart block and signs of congestive heart failure appeared. a, longitudinal section of the heart with the anterior portion removed. The Bjork-Shiley (B-S) prosthesis is partially detached and the ring abscess (arrow) has burrowed through the ventricular septum (VS) into the right ventricle (RV). LA = left atrium; LV = left ventricle. b, rhythm strip obtained shortly before death revealing complete heart block.
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but fortunately it is infrequent. The exact incidence rate is uncertain but it is clearly less than 1 percent annually among patients with prosthetic cardiac va1ves.37~39~45~48 Although prospective studies49*50 have been inconclusive, retrospective studies 16~7~~~5~have shown a reduction in the frequency of early (less than 2 months
after valve replacement) endocarditis coincident with the use of prophylactic antibiotic therapy. Late prosthetic valve infection now appears to be more common than early infection,37v45 presumably because there are now so many persons with prosthetic cardiac valves. Although the mortality rate is high for both groups,
FIGURE 5. Serratia marcescens prosthetic aortic valve endocarditis in a 57 year old man whose infection occurred 4 months after replacement of both aottic and mitral valves. The apparent source of the infection was an intravenous catheter. Left bundle branch block and signs of aortic regurgitation appeared and, despite massive doses of antibiotic agents, he died 3 months after the onset of symptoms of infection. a, view of the aortic prosthesis from above. Infected thrombus is present on its anulus. b, view of the prosthesis as it appeared from the left ventricle. Some of the infected thrombus became detached during excision of this prosthesis at necropsy. The primary orifice is partially obstructed by the infected material. c, opened aortic root, aortic valve and left ventricle (LV) after removal of the aortic prosthesis. Most of the aortic ring is necrotic. In addition, the portion of mitral (M) prosthesis in direct apposition to the aortic anulus also is infected. d, view after excision of the mitral prosthesis showing extension of the aortic anutar infection into the junctional area between the aortic and mitral anuli. LA = left atrium.
FIGURE 6. Staphylococcus epidermidis endocarditis originally involving a Bjork-Shiley aortic valve prosthesis that was excised and replaced with a Magovern prosthesis 28 days before death in a 69 year old man. Fever and signs of aortic regurgitation appeared 7 months after aortic Valve replacement with the Bjork-Shiley prosthesis. After replacement with the t&govern prosthesis, a murmur of aortic regurgitation reappeared. At necropsy, the sewing ring of the Magovern prosthesis had burrowed deeply into the necrotic anulus, causing the ball of the prosthesis to strike the nonnecrotic portion of the aortic wall, probably producing prosthetic aortic stenosis. a, longitudinalsection of the heart through the aortic anulus with the Magovern Drosthesis in Dlace: b. section after removal of the Drosthesis. The frame of the prosthesis has burrowed deeply into the necrotic anUtUS. LA = ieft atrium: LV = left ventricle; MV = mitral valve; dV = right ventricular cavity; i/S = ventricular septum.
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early prosthetic valve infection apparently is more often fatal than late infection.37Jsp45**s Etiology: Most early infections either are incurred at operation or result from a wound infection.25~2g~37~3g~48 Those at operation appear to result from contamination of the cardiopulmonary bypass equipment.53p54 Staphylococcus is the organism cultured most frequently from cardiopulmonary bypass equipment and it is the most frequent cause of early prosthetic valve endoc~ditis.l*,16-1s,25,30~37,39,*4,*5 When gram-negative bacteria or fungi cause endocarditis early, they are usually also recovered from the operating room equipment or from a wound infection.28,3g Late infections usually result from transient bacteremias.37,3g~45~48 Although both staphylococci and streptococci are frequent causes of clinically diagnosed late prosthetic valve endocarditis,37,3g,45 the former have caused most cases of necropsy-proved late endocarditis and the latter relatively few. In none of our 22 necropsy patients was the
AND ROBERTS
infection caused by Streptococcus. Staphylococcus was the most common cause of endocarditis in our patients whether the infection occurred early or late. Blood cultures: Among patients with prosthetic valve endocarditis, blood cultures are almost always positive, except when the infections are caused by certain fungi.27,28,31,32,37,3g,44,45,48Blood cultures were positive during life in each of our 20 patients with endocarditis caused by bacteria and were negative in each of our 2 patients with fungal endocarditis. Blood cultures were positive in only 3 of 39 patients with endocarditis caused by Aspergillus species in a series reviewed by Kammer and Utz.55 Prosthetic valve dysfunction: Signs of prosthetic valve dysfunction are usually present when the aortic prosthesis is infected and usually absent when the mitral prosthesis is infected. Clinical signs of aortic regurgitation were present in 11 of our 15 patients with an infected aortic valve prosthesis. In three of the four
FIGURE 7. Staphylococcus aureus prosthetic mitral valve endocarditis in a 47 year old man who had the onset of symptoms of infective endocarditis 4 months after valve replacement. He had done well during the first 3 months after operation, but symptoms of infection developed after grafting of a cutaneous ulcer. Signs of prosthetic dysfunction were never detected clinically. a, prosthetic mitral valve orifice obstructed by vegetative material, as viewed from the left atrium. b, opened left atrium, mitral anulus and left ventricle after removal of the mitral prosthesis. The entire anulus is necrotic. AV = aortic valve. c, mitral valve prosthesis showing infected thrombus at its base. d, longitudinal section through the left atrium (LA), mitral anulus and left ventricle (LV). The former site of attachment of the prosthesis is designated by the dashed lines. The infective process burrowed through the wall of the heart and caused pericarditis. CA = coronary artery; CV = coronary vein in the right atrioventricular sulcus. e and 1, hematoxylin-eosin-stained histologic sections of the left ventricle remote from the infected mitral anulus. 8, infected embolus in an intramural coronary artery. f, microscopic-sized myocardial abscess. (X400 [e] and X 160 [f], reduced by 24 percent.)
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patients without clinical signs of aortic regurgitation, the prosthesis was not detached at necropsy. Among patients with acute aortic regurgitation, however, classic signs of aortic regurgitation may be absent.s6-5g Signs of aortic regurgitation were not detected in three of nine necropsy patients with prosthetic aortic valve endocarditis described by Madison et a1.,44but all three had prosthetic detachment at necropsy. In contrast, patients with infection involving the mitral valve prosthesis usually have no clinical signs of prosthetic mitral valve dysfunction. Clinical signs of such dysfunction were not detected in any of our seven patients with prosthetic mitral valve endocarditis although the prosthesis was significantly obstructed by vegetative material in five of the seven and partially detached from the anulus in two.i2 McAllister et a1.43 reported on two patients with virtual total obstruction of the mitral prosthesis. Morphologic Features Valve ring abscess: The most consistent morphologic feature of prosthetic valve infection in our 22 pa-
tients was infection behind the site of attachment of the valve prosthesis, resulting in valve ring abscess. Ring abscess was present in each of our 22 patients, and in 14 the infection involved the entire circumference of the valve anulus. In several patients, however, only a portion of the circumference of the valve anulus was involved and, in one patient, histologic examination of the anulus disclosed infection that had not been apparent on gross examination. Extension of the ring infection to adjacent cardiac structures was common, especially when the aortic prosthesis was infected. This extension resulted in the frequent occurrence of both intracardiac fistulas and complete heart block or left bundle branch block. Among nine necropsy patients with prosthetic aortic valve endocarditis described by Madison et a1.,44each had infection at the site of attachment of the prosthesis, and atrioventricular conduction defects developed in 7 (44 percent) of their entire group of 16 patients with prosthetic aortic valve endocarditis. Obviously, it is the occurrence of the infection behind the site of attachment of the prosthesis that makes reoperation so hazardous. Were the infection limited to the interior por-
FIGURE 8. Staphylococcus epidermidis prosthetic mitral valve endocarditis in a 46 year old man who died 16 months after mitral valve replacement with a Starr-Edwards prosthesis. Eight months postoperatively, when he was asymptomatic, cardiac catheterization disclosed normal left atrial pressure and cardiac output. Signs of infection appeared 15 months after valve replacement. Despite antibiotic therapy, fatal congestive heart failure developed. a, mitral valve prosthesis as viewed from the left atrium. A large infected thrombus virtually occludes the mitral valve orifice. b, opened aorta, aortic valve (AV) and left ventricle (LV) showing infected thrombus on the cage of the mitral prosthesis. c, opened left atrium and ventricle showing a completely necrotic mitral valve anulus. The prosthesis has been removed.
FIGURE 9. Staphylococcus epidermidis prosthetic mitral valve endocarditis in a 59 year old woman. The infection appeared IO years after replacement of both mitral and tricuspid valves. At necropsy, only the mitral prosthesis was infected. a, infected mitral valve prosthesis viewed from the left ventricle. Vegetative material (V) is present on the prosthetic anulus just below the aortic valve. b, prosthesis as viewed from the left atrium showing vegetations(V) at the junction of the prosthetic and natural valve anuli. c, same view after removal of the prosthesis showing even greater extensiveness of the infection at the site of attachment of the prosthesis.
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PROSTHETIC VALVE
tion of the prosthesis, excision of the prosthesis should eliminate the infection. Unfort~a~ly, as demonstra~d in our patients and in those described by others,20*35*38,43*44,47 the tissues behind the site of attachment of the prosthesis usually are involved by the infective process. Treatment Replacement of infected prosthesis: The occurrence of a grossly necrotic anulus at the time of reoperation for prosthetic valve endocarditis does not necessarily mean that valve replacement will be fruitless. Although it may be grossly necrotic, the anulus may be free of colonies of organismsand cultures of the necrotic anulus may be negative. In 9 of our 22 patients with prosthetic valve endocarditis and ring abscess, no stainable organisms were found in histologic sections from the prosthetic anulus. One hazard of inserting a prosthesis in a necrotic anulus at the time of valve replacement for prosthetic valve endoc~ditis is b~ro~ng of the sewing ring of the new prosthesis into the necrotic anulus with resulting impingement on movement of the poppet of the prosthesis by adjacent tissue. This sequence occurred in one
ENDOCARDITIS-ARNETT
AND ROBERTS
of our patients and resulted in prosthetic aortic stenosis from inability of the ball to ascend in the cage (Fig. 6). Tissue valve endocarditis: Although prosthetic valve endocarditis in patients with rigid-framed prostheses (the kind present in our 22 patients) usually indicates infection behind the site of attachment of the prosthesis, that is, the sewing ring, ring abscess may be less frequent with endocarditis involving tissue valves. Indeed, in animals and in man, the infective process may be limited to the cusps of the tissue valve, as when infective endocarditis involves natural valves.eQ$el Thus, the chance of cure, either by antibiotic therapy or valve replacement, or both, when infective endocarditis is superimposed on a homograft or heterograft (porcine valve, for example) is much better than when endocarditis involves a rigid-framed prosthesis6i This, then, is an advantage,although a small one, of the tissue valve (porcine) over the rigid-framed prosthesis. Diagnosis: Establishment of the diagnosis of prosthetic valve endocarditis, particularly in the early postoperative period at times may be difficult, as pointed out by several investigators.48s62*63 Diagnosis in the late postoperative period, in contrast, is usually
FIGURE 10. Candida species prosthetic mitral valve endocarditis in a 37 year old woman who underwent valve replacement 125 months before death because of mitral stenosis (mean mitral gradient 7 mm Hg) and regurgitation. Her tricuspid valve was replaced with a porcine xenograft because of severe tricuspid regurgitation 66 days before death. Postoperatively, she required prolonged use of a transthoracic pacing wire, which was the apparent source of the infection. She died from central nervous system embolism. Necropsy disclosed infection of the mitral valve prosthesis. a, mitral valve prosthesis viewed from the left atrium; b, prosthesis viewed from the left ventricle. Large vegetations are present on the base and struts of the prosthesis. c and d, removed mitral valve prosthesis viewed from two different sides showing large vegetations. e, photomicrograph of Candida species in the mitral vegetations. (Methenemine silver stain X860, reduced by 23 percent.) f, photomicrograph of microabscess in the left ventricular myocardium. (Hematoxylin-eosin X80, reduced by 23 percent.)
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made quite readily. 48,62,63 It is worth emphasizing, however, that the combination of fever and a positive blood culture in a patientwith a prosthetic cardiac valve does not always indicate the presence of prosthetic valve infection. We recently studied a patient at necropsy who was diagnosed during life as having prosthetic mitral valve endocarditis on the basis of fever, cerebral episodes consistent with emboli, and one blood culture that grew Staphylococcus epidermidis and diphtheroids. She received antibiotic treatment during most of her 4 month postoperative period and at necropsy no endocarditis was found. A left ventricular aneurysm was present immediately caudal to the mitral anulus and a sterile thrombus was present in the aneurysm (Fig. 11). The latter was the likely source of the cerebral emboli. Antibiotic agents: There seems to be a general view that prosthetic valve endocarditis can at times be cured by antibiotic drugs. For such cure to be established, however, it is necessary that prosthetic valve endocarditis be confirmed during life, and this unequivocal confirmation can be obtained only by examination of the prosthetic valve and its anulus (site of attachment) at reoperation. In other words, to establish cure of prosthetic valve endocarditis it is necessary to be absolutely positive of the diagnosis. Although this confirmation is usually not obtained, it has now been obtained in enough patients to support the view that prosthetic valve endocarditis can indeed be cured in some patients. 16,17,21,23,24,29,30,37,39,44,45,48,64,65
FIGURE 11. Left ventricular aneurysm simulating prosthetic valve endocarditis in a 46 year old woman. She had almost daily fever after mitral valve replacement 4 months before death and one of many blood cultures grew Staphylococcus epidermidis and diphtheroids. The clinical diagnosis was prosthetic valve endocarditis and she was treated with prolonged intravenous antibiotic therapy. She died from central nervous system embolism. At necropsy, an aneurysm was present in the basal portion of the left ventricular free wall. The prosthesis and its anulus were free of signs of infection. a, longitudinal cut of the left atrial (LA.) wall, mitral anulus (A) and left ventricular (L.V.) wall through the aneurysm. b, histologic section of the aneurysm (Movat stain). Thrombus is present in the aneurysm.
TABLE
VI
Comparison
between
Active
Infective
Endocarditis
(IE)
Involving
Prosthetic
Cardiac
Valves and Natural
Mitral Valve
Aortic
Prosthetic no. Necropsy patients (no.) Age (vr) (range and average)
377-65 (52) 3:4 7
Sex ratio (male:female) Underlying valve disease Rheumatic
290
September 1976
100 -
14
4 :
57 0” 29 71 100 0 0
216
%
z
32 27
0 1+ 15 0
: 68 0
7 z
5
* Eighteen of the 52 also had infection aortic valve infection. Floppy mitral valve. Degenerative (5 patients); P <0.05.
no.
z:
endocarditis
no.
3,‘-“,9 (54) 13:2 15 -
32
14 1 1
9” 64 5 5
:, 17
: 77
3
20
that healed (3 patients)
The American Journal of CARDIOLOGY
Volume 38
Valve Natural
%
no.
100 -
52’ 1 J-83 (45) 41:ll 26 4
-
and uncertain
%
50
:;$ 26
2: 19 50
1
7
3
6
9 0 1 12 1 15 5
60 0
13 9
25 17
366 1 21
:9’ 2 40 8
: 12
8: 7 100 33 13
:
k%
of the mitral valve, but in at least 13 of them the mitral valve infection
previous infective
Valves
Prosthetic
22 15-74 (43) 12:10
1
2 5 7 :
Spleen >300 g the + $ 0
%
-
-
Congenital Other None Previous episode I E Infecting organism Staphylococcus§ Alpha streptococcus Pneumococcus Valve regurgitation (from I E) Valve stenosis (from I E) § Valve-ring abscess5 Cqmplete heart block 0 Left bundle branch blocks Organ infarcts
Natural
Cardiac
appeared
origin (2 patients).
31147 19138 to be secondary
6: 50 to
PROSTHETIC VALVE ENDOCARDITIS-ARNETT
Comparison With Endocarditis Involving Natural Valves
Comparison of observations in our 22 patients with prosthetic valve endocarditis with our observations in 74 nonsurgically treated necropsy patients with active infective endocarditis involving natural left-sided cardiac valves disclosed certain clear differences between the two groups (Table VI): (1) Ring abscess was always present in patients with prosthetic valve endocarditis regardless of the site of the prosthesis, but was present in only 30 percent of the comparison group and then, with rare exception, only when the aortic valve was infected. (2) The hemodynamic consequences were different. Prosthetic valve endocarditis caused valve obstruction nearly as often as valve regurgitation, whereas valve stenosis from active infective endocarditis involving natural cardiac valves was extremely rare.le,@ (3) Spread of ring abscess was more extensive in patients with prosthetic valve endocarditis than in patients with natural valve endocarditis, and consequently the frequency of high grade conduction defects was much greater in the former patients. (4) The infecting organism in fatal prosthetic valve endocarditis was most commonly the Staphylococcus. Alpha streptococcus, which remains a common cause of fatal active infective endocarditis in patients with natural cardiac valves, is a rare cause of fatal prosthetic valve endocarditis. Valve xing abscess: Among patients with infective endocarditis involving native cardiac valves, ring abscess when present almost always (95 percent of cases) involves the aortic valve.67 Among our necropsy patients with active infective endocarditis involving a natural aortic valve, 40 percent had a valve ring abscess, whereas only 5 percent of patients with endocarditis involving a natural mitral valve had a ring abscess. In contrast, each of our 22 patients with prosthetic valve endocarditis had a ring abscess. Thus, valve ring abscess is the usual morphologic feature of prosthetic valve endocarditis, regardless of the valve infected. Ring abscesses in patients with infection involving prosthetic valves are generally more extensive than those in patients with active infective endocarditis involving natural cardiac valves. This appears to be a consequence of the rigid nature of the prosthetic frame.
AND ROBERTS
Once the prosthesis is loosened by the infection, the rocking-rigid frame promotes spread of the infection. The greater turbulence across the aortic valve prosthesis probably accounts for the generally more extensive nature of ring abscess with prosthetic aortic than with prosthetic mitral endocarditis. A consequence of this extension is the greater frequency of complete heart block and left bundle branch block in patients with prosthetic aortic valve endocarditis (32 percent) than in patients with natural aortic valve endocarditis (8 percent). Infecting organism: Staphylococcus (either aureus or epidermidis) is the most common cause of prosthetic valve endocarditis (59 percent). Many different organisms cause the remainder of the infections. Although alpha streptococcus was the responsible organism in 17 percent of our 74 patients with natural aortic valve infection, this bacterium was not the causative organism in any of our 22 patients with prosthetic valve endocarditis. Valve dysfunction: The hemod~~ic consequences of prosthetic valve endocarditis vary with the site of the infected prosthesis. Valve regurgitation developed in 12 of the 15 patients (80 percent) with prosthetic aortic valve endocarditis and in 2 of the 7 patients (28 percent) with prosthetic mitral valve infection. In contrast, valve obstruction developed from the infection in 5 of the 7 patients (71 percent) with prosthetic mitral valve endocarditis, and in 1 of the 15 patients (7 percent) with prosthetic aortic valve endocarditis. Among patients with natural left-sided valve infection, 65 percent (64 percent of those with mitral valve disease and 69 percent of those with aortic valve disease) had valve regurgitation from active infective endocarditis, and relatively few (3 percent) had valve obstruction from the endocarditis.lO Thus, aortic prosthetic valve endocarditis almost alv lys causes valve regurgitation and mitral prosthetic valve endocarditis most often causes valve obstruction. Splenomegaly (greater than 300 g) is common both in patients with prosthetic valve endocarditis (64 percent) and in patients with native left-sided valve endocarditis (37 percent). The frequency of infarcts in other body organs is similar in both groups (64 and 70 percent, respectively).
References Roberts WC, Morrow AG: Anatomic studies of hearts containing caged-ball prosthetic valves. John Hopkins Med J 121:271-295, 1967 Roberts WC, Morrow AO: Causes of death and other anatomic observations after cardiac valve replacement. Adv Cardiol 7: 226-247.1972 Roberts WC, BulkfeyBH, Morrow AG: Pathologic anatomy of cardiac valve replacement: a study of 224 necropsy patients. Prog Cardiovasc Dis 15539-587, 1973 Fishbeln MC, Roberts WC, Golden A, et al: Cardiac pathology after aortic valve replacement using Hufnagel trileaflet prostheses: a study of 20 necropsy patients. Am Heart J 89:443-448, 1975 - _ _ .__- -. __ _ __- _ 5. Roberts WC, Fismem MC, Go&tenA: Cardiacpathology after vatve replacement by disc prosthesis. A study of 61 nacropsy patients. Am J Cardiol35:740-760, 1975
6. Fishbein MC, Roberts WC: Late postoperative anatomic observations after insertion of Hufnagel caged-ball prosthesis in descending thoracic aorta. Chest 68:6-l 1, 1975 7. Roberts WC, Hammer WJ: Cardiac pathology after valve replacement with a titting disc prosthesis (Bark-Shiley type): a study of 46 necropsy patients and 49 Bjork-Shiley prostheses. Am J Cardiol 37:1024-1033, 1976 8. Roberts WC, Buchbinder NA: Right-sided valvular infective endocarditis. A clinicopathologic study of twelve necropsy patients, Am J Med 537-19.1972 9. Buchblnder NA, Roberts WC: Left-sided valvular active infective endocarditis. A study of forty-five necropsy patients. Am J Med 53~20-35, 1972 10. Am& EN, Roberts WC: Pathology of active infective endocarditis. A clinicopathologic study of 137 necropsy patients. Current
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PROSTHETIC VALVE ENDOCARDITIS-ARNETT
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Problems in Cardiology, in press. 11. Cohn LH, Roberts WC, Rockoff SD, et al: Bacterial endoGarditis following aortic valve replacement. Clinical and pathological correlations. Circulation 33:209-217, 1966 12. Roberts WC, Morrow A& Bacterial endocarditis involving prosthetic mitral valves. Clinical and pathologic observations. Arch Pathol 82:164-169, 1966 13. Arnett Ek, Roberts WC: Prosthetic valve endocarditis. A study of 18 patients at necropsy (abstr). Am J Cardiol35:120, $975 14. Bj&k VO: Aortic valve replacement. Thorax 19:369-378, 1964 15. Newman WH, Cordell AR: Aspergillus endocardiiis after open-heart surgery. Report of a case and review of literature. J Thorac Cardiovasc Surg 48:652-660, 1964 16. Amoury RA, Bowman FO Jr, Malm JR: Endocarditis associated with intracardiac prostheses. Diagnosis, management and prophylaxis. J Thorac Cardiovasc Surg 51:36-48, 1966 17. Stein PD, Harken DE, Dexter L: The nature and prevention of prosthetic valve endocarditis. Am Heart J 711393-407, 1966 18. Fraser RS, Rossall RE, Dvorkin J: Bacterial endocarditis occurring after open heart surgery. Can Med Assoc J 96: 155 1-1558, 1967 19. Lefferf AC, Hackett RL: Aspergillus aortitis following replacement of aortic valve. J Thorac &rd
292
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42. 43.
44. 45. 46.
47. 48. 49.
50.
5 1.
52.
53.
54.
55. 56. 57.
58.
59.
60.
61.
Starr-Edwards valve: report of a case of bacteriologic cure with antimicrobial therapy. South Med J 66: 1117- 1120, 1973 Hall WJ 3rd: Penicillium endocarditis following open heart surgery and prosthetic valve insertion. Am Heart J 87:501-506, 1974 McAllister RG, Samet J, Mazzolenl A, et al: Endocarditis on prosthetic mitral valves. Fatal obstruction to left ventricular inflow. Chest 66:682-686.1974 Madison J, Wang K, Gobel FL, et al: Prosthetic aortic valvular endocarditis. Circulation 51:940-949, 1975 Wilson WR, Jaumin PM, Danlelson GK, et al: Prosthetic valve endocarditis. Ann Intern Med 82:751-756, 1975 Rubenstein E, Noriega ER, Slmberkofl MS, et al: Fungal endocarditis: analysis of 24 cases and review of the literature. Medicine 54:331-344.1975 Robboy SJ, Kaleer J: Pathogenesis of fungal infection on heart valve prostheses. Human Pathol 6:711-715, 1975 Kloster FE: Diagnosis and ~nage~nt of compli~tions of prosthetic heart valves. Am J Cardiol 35:872-885. 1975 Conte JE, Cohen SN, Roe BB, et al: Antibiotic prophylaxis and cardiac surgery. A prospective double-blind comparison of single-dose versus multiple-dose regimens. Ann Intern Med 76: 943-949, 1972 Goodman JS, Schaffner W, Collins HA, et al: Infection after cardiovascular surgery: clinical study including examination of antimicrobial prophyl~js. N Engl J Med 287:117-123. 1968 Nelson RM, Jenson CB, Peterson CA, et al: Effective use of prophylactic antibiotics in open-heart surgery. Arch Surg 90:731-735, 1965 Herr R, Starr A, McCord CW, et al: Special problems following valve replacement. Embolus, leak, infection, red cell damage. Ann Thorac Surg 1:403-415, 1965 Ankeney JL, Parker RF: Staphylococcal endocarditis following open heart surgery related to positive indicative blood cultures. In, Prosthetic Heart Valves (Brewer LA Ill, ed). Springfield, Ill, Charles C Thomas, 1969, p 719-730 Blakemore WS, McGarrity GJ, Thurer RJ, et al: Infection by airSurgery 70: borne bacteria with cardiopulmonary bypass. 830-838, 1971 Kammer RB, Utz JP: Aspergillus species endocarditis. The new face of a not so rare disease. Am J Med 56506-521, 1974 Wigle ED, Labrosse CJ: Sudden, severe aortic insufficiency. Circulation 32:708-720, 1965 Wise JR, Bentall HH, Cleland WP, et al: Urgent aortic-valve replacement for acute aortic regurgitation due to infective endocarditis. Lancet 2:115-121, 1971 Wise JR Jr, Oakley CM, Goodwin JF: Acute aortic regurgitation in patients with infective endocarditis. The distinctive clinical features and the role of premature mitral valve closure. J Maine Med Assoc 63:273-278, 1972 Mann T, McLaurin L, Grossman W, et al: Assessing the hemodynamic severity of acute aortic regurgitation due to infective endocarditis. N Engl J Med 293:108-113, 1975 Yarbrough JW, Roberts WC, Reis RL: Structural alterations in tissue cardiac valves implanted in patients and in calves. J Thorac Cardiovasc Surg 65:364-375, 1973 Clarkson PM, Barratt-Boyes 80: Bacterial endocarditis following homooraft replacement of the aortic valve. Circulation 42:987-991, 1970-
.
62. SanUe MA, Johnson WD Jr, Hook EW, et al: Sustained bacteremia in patients with prosthetic cardiac valves. N Engl J Med 286: 1067-1070, 1972 63. Weinstein L: Infected prosthetic valves: a diagnostic and therapeutic dilemma. N Engl J Med 286:1108-l 109, 1972 64. Watanakunakorn C, Hamburger M: Staphylococcus epidermidis endocarditis complicating a Starr-Edwards prosthesis. A therapeutic dilemma. Arch Intern Med 126:1014-1018, 1970 65. Walker SR, Shumway NE, Merigan TC: Management of infected cardiac valve prostheses. JAMA 208:531-533, 1969 66. Roberts WC, Ewy GA, Glancy DL, et al: Valvular stenosis produced by active infective endocarditis. Circulation 36:449-451. 1967 67. 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 54~140-145, 1976
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