Aortic Homograft Case Study

Abstract

Objective: The study was conducted to evaluate the long-term results of homograft reconstruction of the left ventricular outflow tract with a cryopreserved aortic homograft in the presence of aortic root abscess associated with a biofilm bacterial infection. Methods: Between January 1987 and December 2003, 161 patients with aortic root abscess underwent freehand aortic valve (FAVR, N=78) and aortic root replacement (ARR, N=83) with an antibiotic treated cryopreserved aortic homograft. Their mean age was 53.1±15.6 years. Endocarditis of the native valve was found in 80 patients and of the prosthetic valve in 81; of the prosthetic valves 49 (60.5%) were mechanical and 32 (39%) bioprosthetic. Aortic ventricular discontinuity was found in 83 patients. The common responsible microorganisms were the biofilm bacteria: Staphylococcus (S. epidermidis: 34, S. aureus: 13) in 47 patients followed by Enterococcus in 23 and Streptococcus in 39. Surgery was urgent in 80 patients and emergent in 81, of whom 44 were in cardiogenic shock. Follow-up totaled 810.8 patient-years (mean: 5.0±4.3 years) and was 100% complete. Results: Operative mortality was 9.3% for elective/urgent and 14.3% for emergency surgery. A total of 7.3% patients died after hospital discharge during the 17-year follow-up period. The actuarial patient survival at 17 years was 70.4±3.6%. Early and late residual/recurrent infections and paravalvular leaks occurred in 4.3 and 2.5%, respectively. Reoperations were carried out in 30 patients, 11 for residual/recurrent infection and paravalvular leaks. Twenty-one patients with FAVR and 9 with ARR techniques underwent reoperation. Early reoperation rate was 4.3%. The actuarial freedom from residual/recurrent infection and paravalvular leaks was 91.6±2.4%. Actuarial freedom from reoperation at 17 years was 75±3.7%. It was 82.9±5.5% for ARR and 63.5±6.7% for AAVR technique. The actuarial freedom from structural valve deterioration (SVD) at 17 years was 98.6±0.4.% at a rate of %/patient-year. Conclusions: Radical debridement of the infected aortic root and homograft ARR offer a low recurrent infection rate and an overall low valve-related morbidity and mortality for up to 17 years. The antibiotic permeable cryopreserved homograft has proven to be resistant to biofilm bacterial infection.

Biofilm bacterial endocarditis, Aortic root abscess, Homograft aortic root replacement

1 Introduction

Since the reports of Wallace in 1965 aortic valve endocarditis is most commonly managed surgically by valve replacement [18]. This disease remains a life-threatening entity and continues to challenge all cardiovascular surgeons. Newly developed second or third degree heart block, pericarditis, echocardiographic and clinical evidence of fistulous communication between the aorta and right atrium or right ventricle, aneurysm of the sinus Valsalvae and mitral incompetence during antibiotic therapy are frequently associated with aortic root abscess. The early recurrent infection rate in these patients with prosthetic valves has not been very satisfactory [4,6].

For over 40 years, the valve of choice for replacing an infected aortic or atrioventricular valve associated with a root abscess has been controversial. In 1972, Ross introduced the aortic homograft for replacing the infected aortic valve which was reported in 1984 [1].

We are presenting our 17-year clinical results of aortic root reconstruction with a cryopreserved aortic homograft in 161 patients with active aortic valve endocarditis with periannular aortic root abscess.

2 Methods

From January 1987 to December 2003, 161 patients underwent freehand aortic valve (FAVR, N=78) and aortic root (ARR, N=83) replacement for active aortic valve endocarditis associated with periannular aortic root abscess. Preoperative characteristics of the study population are shown in Table 1. There were 34 females (21.1%) and 127 (78.9%) males at a mean age of 53.1±15.6 years (range 2–82 years).

Endocarditis of the native valve was found in 80 (49.7.%) patients and of the prosthetic valve in 81 (50.3%); of these prosthetic valves 49 (60.5%) were mechanical and 32 (39%) bioprosthetic. Dehiscence of the ventriculo-arterial junction (ventriculo-aortic dehiscence) by abscess formation was found in 83 patients (51.5%). The sensitivity and specificity for the detection of abscess preoperatively by transesophageal echocardiography were 98 and 100%, respectively. The common responsible microorganisms were Staphylococcus (S. epidermidis: 34, S. aureus: 13) in 47 patients followed by Enterococcus in 23 and Streptococcus in 39. Additional procedures were replacement of the ascending aorta in 8 patients, mitral valve repair in 27, replacement in 9, tricuspid reconstruction in 3 and coronary artery bypass graft (CABG) operation in 10.

Follow-up totaled 810.8 patient-years (mean: 5.0±4.3 years) and was 100% complete.

Indications for surgery were septic shock, cardiogenic shock, intractable sepsis, cerebral, peripheral emboli and congestive heart failure. Surgical technique: after the myocardial protection when CABG was to be performed with saphenous vein or the left internal mammary artery, removal of infected foreign material, valve excision and extensive debridement of the infected and necrotic tissues and the abscess cavity were performed to eliminate the biofilm bacteria or decolonize the biofilm by local disinfection [12–14]. The native aortic annulus was sized followed by the distal coronary anastomoses when necessary.

2.1 Periannular aortic root abscess

Aortic annular abscess. Abscess confined to the aortic annulus in the region of the right and left coronary sinuses was debrided before insertion of an appropriate size aortic homograft as a root replacement. In the presence of relatively small defects the abscess cavity was excluded from the circulation outside the aortic homograft.

Infraannular aortic root abscess. Abscess of the aortic-mitral valvar fibrous continuity: in cases where the aortic annular abscess was extended to the aortic-mitral valvar fibrous continuity reconstruction was performed with the anterior mitral leaflet of the composite aortic homograft (Fig. 1d). A ventricular septal defect was closed by glutaraldehyde fixed equine pericardium.

Supraannular aortic root abscess. Destruction of the aortic annulus extending to the aortic sinuses in the region of the coronary ostia was repaired by pericardium.

After reconstruction of the components parts of the left ventricular outflow tract (LVOT) [19] the homograft is inserted anatomically by freehand (FAVR) or root replacement techniques with a cryopreserved aortic homograft (Fig. 1).

There are some operative technical factors which may influence the early and late outcome of the surgical management of aortic root abscess with and without dehiscence of the ventriculo-arterial junction (ventriculo-aortic dehiscence) with a homograft. Technical causes for reoperation may be associated with: (1) incomplete resection of abscess cavity and necrotic tissues, (2) the use of low quality and undersized aortic homograft [8], (3) continuous running sutures of the proximal anastomosis, (4) subaortic annular implantation of the aortic homograft, (5) reduction aortic annuloplasty by plication of the trigona.

2.2 Implantation techniques

The implantation techniques have been described in detail in our previous report and by others [2,7]. A particular implantation technique of aortic homograft depends on the pathology and geometry of the aortic root and the size of the available aortic homograft as well as the surgeon's preference. An aortic root replacement is preferred when there is a geometric mismatch between the native and the homograft aortic root, because the peripheral commissures to the sinotubular junction of a scalloped undersized homograft will be overextended outwardly after freehand aortic valve replacement (FAVR) to cause central valve incompetence.

The proximal anastomoses of both techniques were performed with single 4-0 sutures with glutaraldehyde-fixed equine pericardial pledgets from ventricle to aorta at the aortic ventricular junction when the aortic annulus was not destroyed by abscess. After closure of the aortotomy the proximal aortic saphenous vein anastomoses were performed.

2.3 Data collection and postoperative follow-up

Data acquisition. Patients were examined at our Institution or have been contacted by means of telephone interview and mailed questionnaire. Further patient data were obtained form hospital records, family doctors and cardiologists. Patients with unknown addresses could be tracked through the district or state registry and the registry of births and deaths.

Follow-up of hospital survivors was complete in 100% of the patients who were available for analysis at a mean of 5.5±4.4 years and 1125 patient-years. They underwent routine echocardiographic studies at 3 and 9 months after operation and thereafter annually. Thirty patients have been reoperated upon for all causes during the postoperative follow-up period at a mean of 1.2 years (range: 1 day–4.35 years). Eleven homografts were explanted due to recurrent infection (7 early, 4 late between 2 months and 4.6 years), 2 due to structural valve deterioration (2 and 4 years) and 17 due to non-structural deterioration (130 days and 6.9 years). Transthoracic Doppler echocardiography was performed in uniform manner and the evaluations were comparable at the different institutions. The postoperative echocardiographic investigations performed during the study period until 30 December 2003 were documented and analyzed. If a patient had undergone more than one echocardiographic or clinical evaluation, the result of the most recent investigation was reported. Recurrent infection and structural and non-structural valve deterioration of the aortic homograft were diagnosed preoperatively by echocardiographic studies and confirmed at the time of explantation.

3 Statistical methods

Tabular data are summarized by the mean and standard deviation for continuous variables and by percentages for categorical variables. Events are defined as valve-related complications or death or other occurrences and determined by Kaplan–Meier actuarial analysis [15].

Differences in actuarial freedom between groups of patients are determined using the log-rank test. Differences in prognostic variables between two groups were evaluated by t-tests for continuous variables and the χ2 or Fisher exact test for categoric variables. Predictors of events during follow-up were identified by means of Cox's proportional hazards regression [16].

All variables listed in Table 2 were investigated for association with hospital death, overall death and valve-related complications at univariate and multivariate analysis.

4 Results

4.1 Hospital mortality

Early (30 days) mortality was 9.3% for urgent and 14.3% for emergency surgery. Forty-four (54%) of the emergency patients were in cardiogenic shock. Low output syndrome or congestive heart failure or both, was the cause of 50% of the early deaths. The other causes of death were: sepsis, multiorgan failure, cardiorespiratory failure and renal failure.

Prosthetic endocarditis, early or late, was not a predictive factor for operative death in the patients with periannular aortic root abscess (hazard ratio: 1.37, confidence interval, 95% confidence limits: 0.78–2.45, P=0.275). Staphylococcal infection was not an independent risk factor for operative death; although the incidence was higher than that of enterococcal and streptococcal endocarditis the difference did not reach statistical significance (hazard ratio: 0.860, confidence interval, 95% confidence limits: 0.476–1.554, P=0.69).

4.2 Late mortality

There were 9 (5.6%) late deaths. The actuarial patient survival including the hospital mortality at 10 and 17 years was 70.4±3.6% (Fig. 2). Recurrent endocarditis was not a predictive factor for late operative death (hazard ratio: 0.249, confidence interval, 95% confidence limits: 0.034–1.800, P=0.174).

4.3 Residual/recurrent infection and paravalvular leaks

Residual/recurrent infection and paravalvular leaks caused reoperation in 11 patients; 7 (4.3%) early and 4 (2.5%) late postoperatively with one operative death. The actuarial freedom from residual/recurrent infection and aortic homograft paravalvular leaks was 91.6±2.4% at10 years with no further events at 17 years (Fig. 3).

4.4 Valve-related complications

4.4.1 Reoperation

Thirty events (7 early and 23 late) occurred postoperatively which led to explantation of homograft valves in 30 patients. Early reoperation rate was 4.3% (N=7), 5 for freehand aortic valve replacement (FAVR) and 2 for aortic root replacement (ARR) patients (Table 3). The mean follow-up until reoperation was 1.2 years (range: 1 day–4.4 years). Eleven homograft explantations were caused by residual/recurrent infection (ARR: 4, AVR: 7), 2 by structural valve deterioration and 17 by non-structural deterioration (ARR: 4, AVR: 13) (Table 4). Actuarial freedom from explantation for all causes at 17 years was 72.7±4.5%; for residual/recurrent infection and structural valve deterioration it was 91.6±2.4 and 98±0.1%, respectively.

Of the 78 patients with the freehand aortic valve replacement (FAVR) technique 21 (26.9%) underwent reoperation; 5 early and 16 late postoperatively; for recurrent infection in 7, non-structural valve deterioration in 13 and structural valve deterioration in 1. Nine (10%) reoperations (2 early and 7 late) were carried out in 83 patients (4 recurrent infection, 4 non-structural and 1 structural deterioration) who underwent aortic root replacement. The actuarial freedom from reoperation at 17 years for FAVR technique was 63.5±6.7% and for ARR it was 82.9±5.5% (P=0.026) (hazard ratio: 2.36, confidence interval: 1.08–5.15, P=0.031) (Fig. 4).

Undersized homografts ≪2mm than the native aortic annulus were revealed as an independent risk factor for reoperation in the patients with aortic periannular root abscess (P=0.0035) (hazard ratio: 0.146, confidence interval (95% confidence limits): 2.263–10.990, P=0.0001). The freehand scalloped homograft technique for AVR was not an independent risk factor for a reoperation (hazard ratio: 0.477, confidence interval (95% confidence limits): 0.202–1.123, P=0.090) unless it was undersized. The root technique was not immune to developing early structural or non-structural deterioration when an undersized homograft was used.

4.4.2 Structural valve deterioration

Early structural valve deterioration occurred in two patients at 2 and 4 years postoperatively, leading to explantation due to valve incompetence.

Thromboembolism and bleeding were not encountered in the 123 survivors.

5 Discussion

Clinical reports claimed that the type of valve implanted may not be as important as radical resection of the abscess and pericardial reconstruction of the left ventricular outflow tract, although the rate of recurrent infection after replacement with a prosthesis is disappointing at 7% [6].

Considering that aortic homograft and pulmonary autograft can restore the anatomic and the physiologic units of the LVOT [1,9,10,19] and have similar biologic attributes we preferred the cryopreserved viable aortic homograft as our valve of choice to manage active endocarditis complicated with annular abscess. A major factor influencing the decision was the fact that we are implanting a true heart valve which will heal in place and be totally permeated with antibiotic solution from the systemic administration of antibiotics.

This report provides the data and outcome of 161 patients with aortic root abscess who were referred late for homograft reconstruction of the left ventricular outflow tract because they were too symptomatic. The paper addresses radical debridement to eliminate the biofilm bacteria in the infected tissues or decolonize the biofilm by local disinfection in order to minimize the incidence of residual and recurrent endocarditis despite effective antibiotic therapy [4,6,7,11]. Over the course of 17 years we were able to identify aspects in which improvements in the surgical management of aortic root abscess with an antibiotic permeable cryopreserved aortic homograft using glutaraldehyde-fixed equine pericardium pledgets were made: curetting of slimy endothelial surfaces of the aortic root, subvalvular left ventricular outflow tract, radical resection of the infected and necrotic tissues and local disinfection. Curetting was reserved for the region of the interventricular septum below the right coronary artery and the membranous ventricular septum in order to avoid A-V block unless resection was necessary. Only three patients needed postoperative pacemaker implantation for A-V block. Early recurrent/residual endocarditis developed in 4.3% and late in 2.5% of cases. This operative strategy is in concurrence with that of d'Udekem and co-workers [4] whereas homograft aortic root replacement provided a low early and late recurrent infection as well as lower reoperation rate, offering a better prognosis for the very sick patients.

Aortic root replacement technique was used in 52% of this series. Aortic homograft with subvalvular muscular skirt and anterior mitral leaflet was used to exclude and exteriorize the abscess cavities and infected tissues of the left ventricular outflow tract was used. This resulted in freedom from reoperation of 82.9% for aortic root replacement and 63.5% for freehand aortic valve replacement (P=0.024). The aortic root replacement technique has therefore proven to be a superior technique.

The 30-day mortality of 9% for elective and 14% for emergency patients in this series of patients with destructive aortic root abscess undergoing root reconstruction is comparable to that reported by other investigators [5,17]. However, it should be noted that over 50% of the patients were in NYHA class IV and in cardiogenic shock at the time of surgery. Concomitant coronary artery bypass graft operation and mitral valve procedures were not predictive risk factors for operative death. Late death (5.6%) was comparatively low (P=0.058) although recurrent endocarditis was the most common cause of death. Actuarial survival at 17 years was 72% as compared with 87% for homografts at 11 years and 61% for prosthetic valves in other series [3,4].

There was a higher incidence of abscess formation in patients with mechanical valves (60%) than with bioprostheses (40%). The most frequent biofilm microorganisms responsible for infection were Staphylococcus (30% of all infections), streptococcus (25%) and enterococcus (13%). Among the patients with staphylococcal endocarditis associated with root abscess 72% were infected by Staphylococcus epidermidis, which is widely respected as a very virulent organism. Although the incidence of staphylococcal endocarditis was higher than that of enterococcal and streptococcal endocarditis the difference did not reach statistical significance (hazard ratio: 0.860, confidence interval, 95% confidence limits: 0.476–1.554, P=0.69). This supports the fact that all the biofilm bacteria can cause abscess formation because they possess surface-sensing systems that induce intracellular signals powerful enough to result in transcriptional and morphological changes for tolerating rapid environmental changes in nutrient availability, carbohydrate source and pH [12–14]. This knowledge and information should therefore modulate echocardiographic and therapeutic decision-making in terms of the likelihood that biofilm bacteria will require early medical/surgical therapy before periannular aortic root abscess develops.

The incidence of recurrent endocarditis with refrigerated (4°C) homografts varies from 81 to 72% at 10 and 15 years, respectively [3]. The report by Petrou et al. of refrigerated (4°C) homografts shows 78% freedom from recurrent infection at 11 years as compared to 91% at 10 years in our series with cryopreserved homografts [2]. The rate of recurrent infection and paravalvular leak in the early postoperative phase (≪60 days) for antibiotic-treated aortic homografts is significantly lower than that of bioprotheses and mechanical valves in which infection is most common in the first 6 weeks postoperatively [4–6]. Our data correlate therefore with the reports in the literature [2,3,7] that the aortic homograft is probably more protective against recurrent infection than prosthetic valves after radical operation where active infection associated with periannular aortic root abscess was present at the time of surgery.

Undersized homograft was identified as an incremental risk factor for reoperation (P=0.0001) [7,8]. Consequently, limited availability of homografts in all sizes and intraoperative accidental damage to a homograft open an option for the use of pericardial-covered stentless bioprostheses such as Shelhigh stentless when a proper homograft size is not available.

6 Conclusions

On the basis of our 17-year clinical evaluation and results we conclude that aortic root abscess can be managed with excellent results by radical resection of all infected and necrotic tissues and local disinfection to remove the responsible biofilm bacteria. Homograft aortic root replacement with or without pericardial reconstruction of the LVOT is preferred to freehand subcoronary aortic valve replacement. The aortic homograft by virtue of its permeability to serum antibiotics has demonstrated to be resistant to biofilm bacterial infection. This surgical technique therefore offers these very sick patients a better prognosis.

Appendix A. Conference discussion

Dr J. Albes (Bernau, Germany): My question is, what should those surgeons do who don't have that easy access to homografts? What kind of graft would you recommend?

Dr Yankah: In the first place, there is now a network of homograft distribution throughout Europe by the Eurotransplant. So you can request and get a homograft size of your choice within 24 hours. In case you don't have the proper size for your patient with aortic root abscess a stentless bioprostheses would be the alternative which are now available on the market. For this purpose we currently use Shelhigh pericardial-covered stentless bioprosthesis which has a similar biological attribute as the aortic homograft. We believe in a completely biological replacement and reconstruction of the left ventricular outflow tract using pericardial-covered stentless bioprosthesis as a complementary aortic valve and root replacement.

Dr J. Sierra (Geneva, Switzerland): What about structural deterioration of homografts, have you had any reoperations on this especially young population of your patients?

Dr Yankah. Unfortunately, I didn't have much time to show you the incidence of structural deterioration. It is very interesting to note that out of the 161 patients, we had only 4 patients who had structural valve deterioration. Therefore there was a very low rate of structural deterioration in this group. The low incidence of structural valve deterioration of cryopreserved homografts in these patients with acute endocarditis needs a further study.

Fig. 1

(a) A cryopreserved aortic homograft: (i) sinotubular junction, (ii) right coronary artery (RCA), (iii) left coronary artery (LCA), (iv) aortic subvalvular muscular skirt, (v) aortic anterior mitral leaflet. (b) Illustration of the aortic homograft: (i) aortic anterior mitral leaflet, (ii) aortic subvalvular muscular skirt. (c) A cross-section of the homograft aortic root demonstrating the anatomic units: (i) sinotubular junction, (ii) left coronary artery (LCA), (iii) right coronary artery (RCA), (iv) aortic valve, (v) ventriculo-arterial junction, (vi) fibrous triangle, (vii) aortic anterior mitral leaflet, (viii) aortic subvalvular muscular skirt. (d) Illustration of surgical reconstruction of the aortic-mitral valvar fibrous continuity with the anterior mitral leaflet of aortic homograft. The abscess cavity is thereby excluded from the blood stream of the left ventricular outflow tract.

Fig. 1

(a) A cryopreserved aortic homograft: (i) sinotubular junction, (ii) right coronary artery (RCA), (iii) left coronary artery (LCA), (iv) aortic subvalvular muscular skirt, (v) aortic anterior mitral leaflet. (b) Illustration of the aortic homograft: (i) aortic anterior mitral leaflet, (ii) aortic subvalvular muscular skirt. (c) A cross-section of the homograft aortic root demonstrating the anatomic units: (i) sinotubular junction, (ii) left coronary artery (LCA), (iii) right coronary artery (RCA), (iv) aortic valve, (v) ventriculo-arterial junction, (vi) fibrous triangle, (vii) aortic anterior mitral leaflet, (viii) aortic subvalvular muscular skirt. (d) Illustration of surgical reconstruction of the aortic-mitral valvar fibrous continuity with the anterior mitral leaflet of aortic homograft. The abscess cavity is thereby excluded from the blood stream of the left ventricular outflow tract.

 

 

 

 

 



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Correspondence address:
Francisco Diniz Affonso da Costa
Rua Henrique Coelho Neto, 55
Curitiba, PR. CEP 82200-120
E-mail: fcosta@mps.com.br

Article received in March, 2006
Article accepted in May, 2006

 

 

Work carried out in Santa Casa de Curitiba, PR.

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