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Endocarditis in patients with bioprostheses: pathology and clinical correlations

Zussa c‘. Galloni MR, Zattera GF, Pansini S, Di Summa M. Poletti GA, Ottino G. Morea M. Endocarditis in patients with bioprostheses: pathology and clinical correlations. Int J Cardiol 1984:6:719-732.

We studied 13 porcine bioprostheses removed from patients with endocarditis at

our institute during the last 4.5 years. All bioprostheses had been removed at

reoperation and were analyzed using anatomical and histological techniques. Each

bioprosthesis was found to have developed rather constant lesions which were not

related to the type of bioprosthesis. The stage of infection was not related to the

duration of implantation. The presence of perivalvular abscesses was an ominous

finding, often being the seat of persistent endocarditis. Our good clinical results of

reoperation lead us to suggest that this be performed early once vahular or prosthetic

malfunction is detected. Bioprostheses are, in our experience, the best choice in the

surgical treatement of prosthetic valve endocarditis.

(Key words: valve replacement; histology: electron microscopy)

Introduction

Endocarditis is. in our experience and of others. one of the main causes leading to reoperation during the first 7 years after cardiac valve replacement with bioprosthe-

0167.5272,'X4,~'$03.00 ’ 1984 Hsewer Scwnce Puhlt\hcrs H V

ses [l-10]. At our institute we always considered titc Goprosthesis as the first choice

in valvular surgery, regardless of the causes of the valvulopathy. because of their IOU

incidence of thromboembolic complications and their excellent hemodynamic per-

formance. The purpose of this study was to search for any correlations between the

clinical data and the pathological changes observed in bioprostheses removed from patients affected by endocarditis. In this way we hoped to establish the best

therapeutic approach to this complication.

Materials and Methods

In the period between January 1979 and June 1983 we performed 1107 valvular surgery operations in which 1045 bioprostheses and 201 mechanical valves were

implanted. During the same period we observed 22 patients suffering from endo-

carditis; in this group, among the 17 patients with a porcine bioprosthesis. 13 needed a new bioprosthetic valve replacement, as did 3 of the 5 patients with a mechanical

valve. Occurrence rates of post-operative endocarditis were 0.7% per patient-year

and, respectively, 0.6% per bioprosthesis-implant-year and 1.5% per mechanical valve-implant-year. The diagnoses were based on at least two of the following

criteria: (1) typical clinical signs (fever. embolism, splenomegaly, new cardiac

murmur), (2) at least two positive blood cultures and/or positive cultures from the annular or bioprosthetic tissue obtained at reoperation. and (3) pathological evi- dence of endocarditis. This study deals with the 13 above-mentioned patients who.

from an etiological point of view. could be divided as follows: two (cases 3 and 12) had endocarditis on a previous mechanical valve implanted in other surgical centers,

Fever. splrnomegaly. new cardiac murmur. M = mitral: Ao = wrtic: T = tncuapld: AF = atriat flhritlatlon;

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one (case 8) had native valve endocarditis while the remainder were affected b> non-infective cardiac disease. Ten were male and three were female. Ages ranged from 25 to 5X years (42 & 12.3). The affected porcine bioprostheses were in aortic.

mitral and tricuspid position in seven cases, five cases and one case, respectively.

The relevant clinical findings are listed in Table 1. Two patients (cases 7 and 13)

were reoperated upon because of suspected primary tissue failure, one having had a

previous mild bout of fever and a new cardiac murmur, the other having had only a new cardiac murmur. The bioprosthescs of these two patients showed bacterial

colonies: in addition in case 7 streptococci were cultured from samples taken from

the valve during operation. Seven patients were operated upon as emergencies or with urgency (within 72 hr of presentation at our surgical center). The remaining

patients underwent elective valve replacement. Two patients died within 30 days after surgery because of respiratory insufficiency and multiple preoperative mycotic emboli. Three had persistence of endocarditis while all others promptly recovered

from the infective process. Long-term follow-up (6 to 55 months. 22.9 & 17.7) shows no late deaths.

The removed bioprostheses were fixed in 3’0 glutaraldehyde in phosphate buffer

(0.1 M; pH 7.3) and were X-rayed with mammographic films (25 mA. 37 kV, 0.3 .sec). Gross and low power examination was carried out using a stereomicroscope in

transmitted polarizing light. Specimens from each bioprosthetic leaflet were pre-

parec for optical microscopy by post-fixation with 109’ neutral buffered formalin. They were then embedded in paraffin and sectioned at 5 pm thickness. The sections

were stained with hematoxylin-eosin. Weigert-Van G&on. Gram, Grocott and Von

Kossa techniques. Further specimens were taken for scanning electron microscopy and were dehydrated in a graded alcohol series. critical point dried in liquid CO,

and sputter coated with gold. They were examined with a Cambridge Stereoscan 100 scanning electron microscope.

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7’3

Results

Operative Findings

l‘hrombotic Vegetations

Thrombntic vegetation\ \vere variable in distribution and size in the three Itsatlas

of valves inserted in either atriowntricular or aortic position (Table 2). there king

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no significant difference between inflow and outflow surfaces in either position. Massive thrombosis (covering all the area of at least one leaflet) was found in three

of the five cases of streptococcal etiology. This finding was not related to either the

position of the valves or the duration of implantation or the duration of endocardi-

tis. From the morphological viewpoint (excluding the fibrous layer which is the

normal product of the biological interaction between prosthetic valve and host) we observed two main patterns of thrombus considered likely to be of inflammatory

origin. One had a friable, cauliflower-like form (Fig. 1). and the other a Iaminar. smooth and compact one. The Iaminar thrombus in two cases showed finger-like

appearance due to various fibrinous layers lying over each other.

Lacerations

Tears were present in six of seven bioprostheses inserted in aortic and in three of six in atrioventricular position. Table 2 shows the distribution of the various types of

tears in each bioprosthesis according to the classification suggested by Ishihara et al. [l I]. Typically. type I lesions (tears involving the free edges) were close to the nodules of the leaflets. In three of these, the confluence of two such tears caused the loss of the nodule (Fig. 2). Radiographs show calcifications in 80’3 of lacerated

leaflets (12/l 5).

Calcification

Calcification was found in 3X.5? of left cnfonary leaflets (S/13) and in 53.8% 01

the other two leaflets (14/26); 6?.lF of calcified leaflets were also torn. Calcium was found both in leaflets and thrombi. vq ing from small granules to rnah.si\,e deposit>

which immobilized the affected leallt’t~ ( Fig. 3).

Inflammatop Cell Infiltration

This was present in 76.90; of leaflets. being present on both the surfaces and Lvithin the inner connective tissue layers (Table 3). In one case. when the valve had

been removed early (case 10). abundant deposits of inflammatory cells were found onlv on the surface. The inflammatory infiltrate wx made up of macrophuges.

Fig. 3. Case 8. Radiography of massive calcific deposits

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neutrophils, plasma-cells. giant polynuclear ce1l.s and. in a Gngle case. eaainophils

(Fig. 4). These cells uere always present in the thrombotic \‘tb loetationa superimposed

on both surfaces of the bioprosthesis.

Etiological Agents

They were identified in nine valves. being located deep in the leaflets in se\vn: this location corresponds to the third stage of bioprothetic infection evolution

described by Ferrans and colleagues [12]. Histology showed bacterial colonies within the biological parts (leaflets and aortic wail) of the bioprostheses and in the thrombi (Fig. 5). Often these colonies lay close to areas of altered connective tissue huch a:, homogenization. altered staining and cavities. These features were also demonstrated in the two cases reoperated because of presumed primary tissue failure. Scanning

Fig. 5. Case 7. Bacterial colonies near the outflow surface of the non coronary leaflet (Gram stal

magnification 117 X ).

Fig. 6. Case 12. Bacteria observed in the right coronary leaflet, Inflow surface (SEM. magnification

4511X).

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clrctron microscopy revealed the bacteria on the surfaces of these specimens (Fig. 6). Case 1 (with mycotic etiology) was characterized by an onion-like layered thrombus (Fig. 7). Scanning electron microscopy showed this to consist mainly of fungal hyphae, with a shape characteristic of their phasic growth. Rough and brush-like

areas were found with exposed hyphae (Fig. 8) and other areas with smooth fibrin.

Connective Tissue Alterations

Loosening and disruption of the fibrous tissue layers were found in all valves which had been implanted for at least 2 months. The only case without these changes had been implanted for 1 month only.

F’lg. 7. Car 1. Mymtu mien-lihe layered thrombus infiltrating the leaflet (arrows) (Grocott stain. m.ignlfiution 29 x ).

Discussion

We noted that infection of bioprosthetic valves is characterized by rather constant and comparable morphologic lesions no matter which type of valve (Hancock,

CarpentierEdwards, Liotta) had been used. Nevertheless. some etiological agents

produced more specific lesions such as thrombosis, which is always present as vegetations in the mycotic infection whilst perivalvular abscesses are more frequently associated with Srqlz~~lococ~cus infections [13,14]. The stage reached by the infection was not related to the duration of implantation, to the duration of endocarditis or to any particular etiological agent. The pathological findings and the clinical evolution

are similar in bioprosthetic and native valve endocarditis [2,3,5-7,12.13.15--IS]. This persuaded us. therefore, to adopt the same therapeutic approach for bioprosthetic and native valve endocarditis. Thus, in the presence of either valvular or prosthetic malfunction, we usually suggest early operation because we agree that. in the presence of a significant hemodynamic dysfunction, be the patient symptomatic or not. any surgical delay could prove to be useless or even dangerous [1.14,19---221. The less dramatic evolution of the endocarditis on a bioprosthetic valve compared with that when there is involvement of a mechanical valve. is rather typical; from our viewpoint. such behavior could depend on the presence. in the bioprosthesis. of three

731

moving components all of which are very unlikely to malfunction at the same time. Bioprosthetic endocarditis. in our and others’ experience, is rarely complicated by

perivalvular abscesses and so by perivalvular leaks; on the contrary they are frequent in mechanical valve endocarditis and cause the rapidly progressive hemodynamic deterioration of the patients [335,8,13,19]. Moreover abscesses are the most frequent

cause of persistence of the infection; in fact, among our four cases of annular abscesses in bioprosthetic valve endocarditis, two had developed during a previous

mechanical valve endocarditis. Furthermore, they produce annular alterations that,

after valve replacement, may result in later paraprosthetic leaks even if the infection is eliminated. Finally the validity and effectiveness of our therapeutic approach is

confirmed by the good results we achieved in the surgery of the native valve

endocarditis. In fact, at our institute, 21 patients affected by active native valve

endocarditis received 17 bioprostheses and 4 mechanical valves (one double valve

replacement) and one patient underwent a conservative procedure: among the 19

patients discharged from hospital, we observed progressive hemodynamic deteriora-

tion, that necessitated valve replacement in only the patient previously treated with the conservative procedure. In the other patients the endocarditis resolved. Late

follow-up showed reinfection after 2 years of well-being in one, a drug addict. Thus far we are satisfied with our results (2 deaths in 13 cases of bioprosthetic infection).

We suggest that the present results support our choice of bioprostheses as the optimal valve for the surgical treatment of both native and prosthetic valve endo- carditis.

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