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Eur J Cardiothorac Surg 2002;21:260-267
© 2002 Elsevier Science NL
Department of Cardiothoracic and Vascular Surgery, Humboldt University Berlin, Deutsches Herzzentrum Berlin, Augustenburger Platz 1 D-13353 Berlin, Germany
Received 18 September 2001; received in revised form 25 October 2001; accepted 2 November 2001.
* Corresponding author. Tel.: +49-30-4593-2021; fax: +49-30-4593-2021
e-mail: yankah{at}dhzb.de
| Abstract |
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60 days) and late reinfection rate was 2.7 and 3.6%, respectively. Freedom from reoperation for matched and undersized homografts at 1013 years was 85 and 55%, respectively. The univariate model identified undersized homograft (P=0.002), FSCI (P=0.09) and reinfection (P=0.0001) as independent risk factors for developing early and late valve dysfunction resulting in reoperation and homograft explant. Conclusion: Early aggressive valve replacement with homograft for active infective aortic root endocarditis with periannular abscesses is more successful than delayed last resort surgery. Homografts exhibit excellent clinical performance and durability with a low rate of reinfection, if properly inserted. Undersized homograft is an incremental risk factor for early and late reoperation.
Key Words: Valvular endocarditis Homograft replacement Sizing techniques
| 1. Introduction |
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The low rates of recurrent endocarditis in both drug and non-drug addicts raised questions regarding the well-known established surgical principle, that it is unwise to place prosthetic materials into an area of active infection.
Surgical excision of infected valve tissue, drainage of myocardial abscesses and removal of necrotic materials provide some of the standards of aggressive surgical treatment of active infective endocarditis frequently caused by virulent organisms such as gramm-negative bacteria, Staphylococcus aureus, epidermidis and fungus which are unresponsive to antibiotic therapy alone [2,15].
The use of homograft to replace the infected aortic valve or root to restore the anatomic unit [17,24] therefore fulfills the surgical principles by virtue of its natural biocompatibility to absorb antibiotics and excludes them to disinfect its surrounding tissue. It excludes the periannular abscesses and necrotic tissues of the aortic root from the blood stream, subsequently brings the aortic root infection to healing.
The implantation and sizing techniques of homografts employed to handle the aortic root infection varies and the choice depends on the surgeon [4,5,6,10,16,17,23,24].
The study evaluates the long-term clinical results and the incremental risk factors for developing early and late homograft valve failure in patients with active infective aortic root endocarditis. From this assessment, an improved understanding of additional mode of failure to improve the clinical results may emerge.
| 2. Material and methods |
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3 mm) and undersized (
3 mm) in relation to the difference in size between the homograft and the recipient aortic root. One hundred and twenty patients received matched, 27 oversized and 35 undersized homografts. The homografts (-80 and -170°C storage temperature) were acquired from our hospital based, BioImplant Service of Leyden, European homograft and Barcelona homograft banks [24]. | 3. Preoperative findings |
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The preoperative diagnosis was established by positive blood cultures and confirmed postoperatively by histology and cultures.
Microorganisms grown were: Staphylococcus aureus, 25.3%; Staphylococcus coagulase negative, 12%; Streptococci (viridans, mites, bovis, sanguis and beta-haemolytic), 32%; Enterococci, 20%; Pateurella multocida, 1.1%; Actinobacillus, actinomycetem comitans, 1.1%. Negative cultures were diagnosed in 12%. Patients presented with negative cultures received ampicillin, rifampicin and gentamycin.
In 110 (60.4%) patients, the preoperative New York Heart Association (NYHA) functional classification was III and in 72 (39.6%) was IV, including cardiogenic shock. Five (2.7%) patients suffered from cerebral (n=3 with abscess in two) and peripheral (n=2) septic embolism. One hundred and twenty (65.9%) patients presented with infection under antibiosis with or without abscesses but with unstable hemodynamics as compared to 62 (34.1%) with persistent sepsis. Duration of antibiosis prior to surgery varied. Fifty-five (30.2%) patients underwent antibiotic therapy less than 2 weeks and 127 (65,9%) 23 weeks prior to surgery. Twenty-four patients (13%) patients presented with renal insufficiency.
In the five patients who presented with neurologic symptoms, brain scans were performed to confirm cerebral ischemia and exclude an intracerebral abscess. However, the cardiac system is treated preferentially although an aggressive approach to intracerebral abscess to rid the body of residual infection by the neurosurgeons is preferred.
| 4. Technique of homograft implantation |
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Aortic root endocarditis with extensive annular and subannular destruction by abscesses was treated by root replacement technique by anastomosing the lower suture line of the trimmed homograft conduit with the lower margin of the abscess cavity in the left ventricular outflow tract in the area of intact endocardium avoiding injury to the His conducting tissue.
The shape and the length of the subaortic curtain and the anterior mitral leaflet of the homograft was trimmed and prepared to fit the aortic root geometrically without creating tension on the lower proximal suture line and annulus distortion when it is inserted to reconstruct the left ventricular out flow tract. The ascending aortic segment of the homograft conduit was used for replacing the native ascending aorta [9,17].
Additional procedures were: reconstruction of the mitral and tricuspid valves, 23 (12.6%); aortic-mitral septum, 17 (9.3%); aortic-ventricular discontinuity, 58 (31.9%); replacement of the mitral valve, 15 (8.2%); replacement of the ascending aorta, 6 (3.2%) and closure of VSD, 8 (4%). Two patients (1.1%) received coronary bypass graft each to the right and left anterior descending, respectively, due to dysfunction of the left and right ventricle during weaning the heart off bypass. The ventricle dyskinesia in both patients was confirmed by intraoperative echocardiography. The myocardial revascularization and reperfusion allowed successful weaning off bypass with moderate inotropic support.
| 5. Follow-up patients |
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| 6. Statistical methods |
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| 7. Early results |
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| 8. Late survival |
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| 9. Recurrent endocarditis |
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| 10. Reoperation |
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Actuarial rate for freedom from reoperation for FSCI technique at 10 and 13 years was 68% and for ARR at the same time interval was 78%. Freedom from reoperation in abscess cohorts was 86% at 1 year, 65% at 7 and 10 years. FSCI and undersized homograft revealed risk factors (P=0.09, P=0.002) for reoperation. Reinfection was a significant, independent risk factor for reoperation, which was associated with perivalvular leak and pseudoaneurysmal formation (P=0.0001, Table 1), while an abscess alone did not show a predictive factor for reoperation (P=0.11, Table 1, Fig. 4).
| 11. Discussion |
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The general improvement and standardization in homograft harvesting and processing has optimized the overall quality of homografts while standardization of implantation technique appears to provide significant improvements in the long-term clinical performance [4,6,9,16,23].
The rate of prosthetic valve endocarditis following a prosthetic valve replacement of infective aortic valve endocarditis with annular abscess in the late 1980s was as high as 18.5% as compared to 4% for homograft valve substitute. The results of this study, which was presented at the 5th annual meeting of European Association of Cardio-thoracic Surgery in 1991 in London, changed our policy to use aortic homografts for infectious aortic root abscesses. The adopted surgical approach with homografts using the freehand subcoronary and root replacement subsequently improved our patient survival and morbidity rate [24]. Both implantation techniques (FSCI and RR) have been in use for over 39 years [3,20] and several reports of long-term results have been published [1,8,10,11,16].
The choice of a specific implantation technique for homograft depended on the extent of aortic root (annulus, subannular structures valve leaflet and the sinuses of Valsalva) destruction as well as the relationship between the length, geometric size and shape of the available homograft and the recipient aortic root [16,17,24].
The non-coronary sinus of the homograft can be used to enlarge or remodel the aortic root when necessary [17,20,24]. If incidentally after excision of the infected valve and debridement of the necrotic tissue, there is only undersized homograft available, a root replacement technique is indicated where the homograft is inserted as a conduit with reimplantation of the coronary arteries [4,6,16,17,23,24]. Implementation of this policy varied in emergency situations.
The anterior mitral leaflet of the aortic homograft or a pulmonary homograft wall patch as well as a glutaraldehyde fixed equine pericardium can be used to exclude the orifice of a large abscess cavity from the circulation, whereas for the reconstruction of jet lesions of the native anterior mitral leaflet or VSD, equine pericardium is used prior to insertion of the homograft root [4,5,8,10,24].
Focussing specifically with the incidence of early homograft valve failure as a function of implantation technique, some interesting trends were apparent. Among the 31 patients who underwent reoperations for valve dysfunction and residual infection, 77.4% received FSCI as compared to 22.6% with RR technique. Assuming all other factors to be equal for the homografts and for both implantation techniques, our analysis revealed that early valve dysfunction and reinfection was associated with the use of undersized homograft and FSCI technique (Table 1). These findings concur with other reports [1,16,17,23] that properly sized competent homograft is less turbulent and demonstrates more resistance against reinfection [17,25] when active infective aortic root infection is extensive.
Other authors found no differences in their series. Possible explanations for the conflicting morbidity data in the reports of others may include the lack of discrimination of geometric size differences between the homograft and the native aortic root in the univariate/multivariate analyses for potential risk factors for reoperation [8,10,11]. Many of the variables examined in our study are interrelated, the univariate models could allow identification of FISCI technique, undersized homograft as independent risk factors closely associated with active infective aortic root endocarditis with periannular abscesses, early and late aortic homograft valve incompetence, reinfection and reoperation. Homograft valve incompetence, which developed in aortic position, was usually related to malposition, root distortion or overstretching of the commissural posts at freehand subcoronary implantation, leading to leaflet malcoaptation and central leak. There are other surgical factors, which may cause reinfection such as inadequate debridement of necrotic tissues and local disinfection of abscess cavity (left coronary and non-coronary annular abscesses, aortic-mitral septum abscess) prior to exclusion from the circulation.
The trend in the long-term performance of the undersized homograft shows a progressively increasing rate of valve failure after 5 years of follow-up due to either leaflet prolaps or progressive loss of leaflet extensibilitiy, which is peculiar to both implantation techniques [4]. Although the number of patients at risk beyond 7 years is small in the series, there is an obvious disparity in the performance past 7 years, between the matched and undersized homografts which has been also observed in patients with prosthetic-patient mismatch [19]. Timing of reoperation of these patients, however, depends on a number of patient-related factors, most importantly on the impairment of the left ventricular function.
We observed abnormal bleeding and acute renal failure as postoperative morbid events in our patients with acute infective endocarditis with sepsis although the incidence was very low, it is worthy of mentioning it. Despite a normal platelet count, these patients with abnormal bleeding have a defect in platelet aggregation. Penicillin and cephalosporins can inhibit ADP, collagen and thrombin-induced platelet aggregation and the platelet release reaction by coating platelet. The defect is a result of the uncontrolled sepsis and therefore it is prudent and mandatory to test platelet function at least by bleeding time, in all patients undergoing surgery for active infective endocarditis and have platelet transfusions available for those patients with abnormal platelet function preoperatively [2,5]. Patients with acute renal failure due to acute infective endocarditis carry a high risk of early postoperative death. In our series, these patients could be treated with hemofiltration with a success rate of 87.5% by the time of discharge.
Survival rate of patients in the study is not different from that reported with other homograft valves at similar durations of follow-up [6,8,10,17,23,24].
We noted a difference in mortality depending on whether surgery was undertaken in patients with infection before 3 weeks of antibiotic therapy had been completed or after treatment was complete. For those patients who had completed antibiotic treatment and in NYHA class III, the operative mortality rate was 8.5%, while for those with uncontrolled active infection despite antibiosis in heart failure with NYHA class IV, the mortality rate was 14.5%. The increased risk of operation when the infection is active is therefore related to more severe underlying heart failure and late referral of symptomatic patients as well.
The late survival was determined by two related factors the patient and the implanted homograft. Three modes of late death were identified in our study: two are related to the implant i.e. valve incompetence due to undersizing and homograft valve endocarditis resulting in reoperation. The third mode of death is myocardial infarction due to coronary artery disease. This raises the question whether coronary angiography should be performed preoperatively in patients with active infective aortic root endocarditis with history of angina pectoris, where the risk of embolization from vegetations is low [21] or postoperatively prior to discharge or thereafter if there are symptoms of angina.
We have relied on the clinical examination and findings and echocardiogram for preoperative evaluation in most of our patients with valve incompetency who require surgery [1315]. Cardiac catheterization is used to evaluate patients with suspected underlying coronary artery disease. In presence of coexisting coronary artery disease, coronary artery grafting might be beneficial in patients with hemodynamic relevant coronary artery stenosis as experienced in two of our patients.
Freedom from thromboembolism was 100% over the entire follow-up period despite the lack of anticoagulation and this compares favorably with other reported series [1,10,11,13,16,17,23,24]. However, when one or more factors associated with an increased risk of thrombo-embolism (atrial fibrillation, enlarged left atrium with or without thrombus) are present, patients with homografts who develop such risk factors should be anticoagulated. This recommendation, based on the clinical results with porcine bioprosthesis, holds true for stentles tissue valves as well [12].
According to the results of our clinical study, properly inserted homografts in aortic position for active infective root endocarditis has an excellent clinical performance over 13 years and is superior to bioprosthetic or mechanical valve in similar patients with aortic root infection and periannular abscesses [5,12]. Currently, alternative stentless xenograft valves are in use with good clinical results [22], however the long-term results are not yet available. Aortic root replacement is preferred for infected aortic root with annular and aortic outflow destruction.
The presence of abscess cavities appeared not to be an independent risk factor for recurrent endocarditis, early or late death. This is due to the fact that the infectious tissue and abscess were brought to healing after excluding the abscess cavity from the systemic blood circulation with antibiotic treated properly sized homograft. In the final analysis, it appears therefore that early referral of patients with effective antibiotic pretreatment and aggressive surgical approach contributed to the success rate of our patients.
Early and late homograft failures were associated with undersized homografts available at the time of surgery and in most cases with the freehand subcoronary implantation technique. Homograft reinfection was observed to be frequent with undersized homografts and was associated with perivalvular leak and pseudoaneurysmal formation.
In conclusion, early referral of patients with acute endocarditis under appropriate antibiotic treatment and aggressive surgical therapy will improve the surgical results significantly. Undersized homografts should be avoided for aortic valve replacement and for any implantation technique irrespective of the aortic root pathology. It is prudent therefore to use a stentless xenograft, which is readily available in all sizes as an alternative valve substitute when undersized homograft is available at the time of operation and a pulmonary autograft operation (Ross operation) is not requested or indicated [18].
| Acknowledgments |
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| Footnotes |
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| Appendix A. Discussion |
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Dr Yankah: We have about 12% negative cultures. These patients get rifampicin, ampicillin and gentamycin.
Dr Wolner: For how long?
Dr Yankah: Up to the time when the CRP is low or becomes normalized. Usually an average of about 34 weeks.
Dr D. Metras (Marseille, France): I am amazed by your conclusions, because seeing the striking difference between the results of the freehand and the total root in homograft replacement, I would have expected a recommendation of using a total root replacement rather than recommendations depending upon the concept of undersizing, and a recommendation of using a bioprothesis.
Dr Yankah: The message today is the incidence of postoperative valve incompetence with undersized homografts in this new series presented, which I think is not well addressed in the literature. Postoperative valve incompetence does not only relate to implantation technique but also to improper sizing. Usually, it is a combination of patient and valve related factors; the pathology of the native aortic root or the clinical condition of the patients undergoing such an emergency operation, and available homograft size selected for implantation. Analysis of homografts implanted at emergency surgery showed a great number of undersized valves especially the imported valves, subsequently the improper sizing technique was also the cause of early reoperation due to valve incompetence in patients with freehand subcoronary technique. We advocate therefore, in such a situation, a homograft root replacement, because the early postoperative morbidity is low with the root technique. So if you have an undersized homograft you have no choice but to perform a root replacement.
Dr R. Benetis (Kaunas, Lithuania): The question is regarding your second conclusion about the xenografts as a root replacement. Do you have some solid data showing that stentless xenografts would play the same role as homografts in the case of endocarditis?
Dr Yankah: We know in the literature of the long-term results of bioprosthetic valves, which go in parallel with the homograft results. On the basis of this knowledge, we assume and expect similar or same results with a stentless homograft. So as an alternative biological valve, instead of using undersized homografts, we prefer now to use stentless xenografts for acute endocarditis with periannular abscesses which is an ongoing clinical study.
Dr A. Moritz (Frankfurt, Germany): Dr. Yankah, I just have a short technical question. If you do a root replacement, the size mismatch actually is not really existent. If you have a smaller homograft than the root size is, then you just plicate the root a bit and it will fit. So I assumed that your bad results with the undersized homografts came only from the subcoronary group. If we don't have a matched homograft, we adapt the root to the size of the homograft. We do this routinely and see good results.
Dr Yankah: Well, first, I will not perform any tailoring of the aortic root and we do not practise it for endocarditis with periannular abscess because the valve related morbidity would be higher. Of course, you can use root replacement for a homograft even if it is undersized, as I mentioned, the long-term result of such a valve is not favorable. I don't have time to show you a slide of an early degeneration of an undersized homograft used as a root. In conclusion, I would like to stress that undersized homograft for a root replacement is not immune to early degeneration, therefore it should be avoided.
| References |
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