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Ann Thorac Surg 2005;79:767-771
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Cryopreserved Aortic Viable Homograft for Active Aortic Endocarditis

^a Department of Cardiac Surgery, Hôpital Européen Georges Pompidou, Paris, France
^b Department of Microbiology, Hôpital Européen Georges Pompidou, Paris, France
^c Department of Anaesthesiology-Reanimation, Hôpital Européen Georges Pompidou, Paris, France

Accepted for publication August 5, 2004.

^* Address reprint requests to Dr Grinda, Department of Cardiac Surgery, Hôpital Européen Georges Pompidou, 21 rue Leblanc, 75908, Paris Cedex 15, France (E-mail: jean-michel.grinda{at}egp.ap-hop-paris.fr).

	Abstract

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BACKGROUND: To evaluate the short and long-term results of cryopreserved aortic viable homograft (CAVH) in the treatment of active aortic endocarditis.

METHODS: From January 1992 to December 2002, 104 patients (23 females, 81 males) with a mean age 51 ± 13 years (from 14 to 77) underwent CAVH replacement for active aortic valve endocarditis. Seventy-six patients (73%) had endocarditis of the native aortic valve, 28 (27%) had endocarditis of prosthetic aortic valve; among them, eight had a recurrent infection. Eighty-three patients (80%) had isolated aortic endocarditis. Plurivalvular endocarditis was observed in 21 (20%) patients, (aortic and mitral in 16 patients, aortic and tricuspid in 5). Intraoperative transesophageal echocardiography was systematically used. Anatomical lesions included perforations in 89 (86%) patients, vegetations in 79 (77%) patients and periannular extensions in 60 (58%) patients. Precise bacteriologic diagnosis was available in 82 (80%) patients.

RESULTS: Cryopreserved aortic viable homografts were inserted using the aortic root replacement technique in 93 (89%) patients and the subcoronary technique in 11 (11%) patients. Associated procedures were performed in 38 (37%) patients: mitral (n = 23) and tricuspid (n = 3) valve repair, partial homograft mitral valve replacement (n = 3), partial homograft tricuspid valve replacement (n = 3), coronary bypass graft (n = 3), and ascending aorta replacement (n = 3). Hospital mortality was 5 (5%) patients. Causes of death included: myocardial infarction (n = 2), myocardial failure (n = 2), and multiorgan failure (n = 1). During follow-up (61 ± 36 months, from 6 months to 136 months), 9 secondary deaths occurred (2 were cardiac related), 14 aortic valvular redo surgeries were performed (2 for nonstructural failure, 6 for structural failure, and 6 for endocarditis). Actuarial survival at ten years was 83%, with 93% of the patients free from cardiac death. At ten years, actuarial rate for freedom from reoperation was 76% and freedom from recurrent endocarditis was 93%. No thromboembolic complications were observed.

CONCLUSIONS: The CAVH has proven its effectiveness in treating the destructive lesions of active aortic endocarditis. It has provided satisfactory immediate and long-term results. Allowing the possibility to avoid a prosthetic material, CAVH could represent an option for surgically treating active aortic endocarditis more rapidly.

	Introduction

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Whereas elective surgery for infectious endocarditis sequelae lesions uses simple techniques with satisfactory results, surgery for active endocarditis remains an issue [1–11]. Active endocarditis, on native valves and even more on prosthesis, is often associated with major destructive lesions [1, 2, 3, 5–9, 12–14]. Prosthesis implantation, despite the various technical artifacts, is particularly difficult, with a high reinfection and mortality rate [1–4]. Aortic homograft interest has already been documented for this indication [5–10, 12, 13, 15–19]. We have used cryopreserved aortic viable homografts (CAVH) in such active aortic infective endocarditis. We now study the immediate and long-term results of such procedures.

	Material and Methods

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Population
PATIENTS
From January 1992 to December 2002, 104 patients (81 male, 23 female, mean age 51 ± 13 years; range, 14 to 77 years) underwent CAVH replacement for active aortic infective endocarditis (Table 1).

Twenty nine (28%) patients were at risk of infection because of extracardiac conditions compromising host defense: toxicomania (n = 8), HIV (n = 4), leukemia (n = 3), corticotherapy (n = 4), dialyzed chronic renal failure (n = 3), diabetes (n = 4), and alcoholism (n = 3). No cardiac or extracardiac predispositions were found in thirty (29%) patients.

SYMPTOMATOLOGY
All patients presented with general condition impairment and a septic state; they had already undergone explorations and intravenous antibiotic therapy. Many patients were critically ill at the time of operation. Fifty-eight (56%) patients were in New York Heart Association class III and 46 (44%) were in class IV including cardiogenic shock. Twenty-one (20%) patients had already presented with one or several embolic complications: brain (n = 9), upper or lower limbs (n = 4), splenic (n = 6), coronary (n = 2) embolism. Twenty-one patients suffered from severe renal failure and twenty-nine patients required preoperative mechanical respiratory support.

Diagnosis
ECHOCARDIOGRAPHY
Intraoperative transesophageal echocardiography (TEE) was systemically used to check valvular dysfunctions and endocarditis damage (vegetations, perforations and cusp destructions, perivalvular leaks, abscesses, and other periannular extensions), and assess ventricular function and result of the surgical procedure.

TOPOGRAPHY
Endocarditis lesions were located on either one or several valves. Eighty-three (80%) patients suffered from an isolated aortic infective endocarditis. Endocarditis damage involved two orifices in 21 (20%) patients (aortic and mitral valves in 16 patients and aortic and tricuspid valves in 5 patients) (Table 1).

NATIVE VALVE/PROSTHESIS
Native valve endocarditis (NVE) was observed in 76 patients (73%), prosthetic valve endocarditis (PVE) in 28 patients (27%) (Table 1). Fifteen bioprostheses and 13 mechanical prostheses were affected by PVE. Delay between prosthesis implantation and reintervention for PVE was 6 ± 4 years (range, 1 month to 16 years). In 8 patients early endocarditis developed less than two months after prosthesis implantation.

BACTERIOLOGY
A precise bacteriologic diagnosis was obtained for 93 (89%) patients. Germ identification was performed preoperatively in 84 cases (mainly from hemoculture results and in one case from arterial embolectomy fragments). Causative microorganisms are summarized in Table 2. The most encountered microorganisms were streptococci (n = 64), and staphylococci (n = 18) without any statistical difference between the PVE and the NVE groups. Despite repeated hemocultures, examination of the explanted infected valves, serodiagnostics, and techniques of cellular microbiology, no organisms were identified in 11 (10%) patients.

Surgery
SURGICAL TECHNIQUES
Conventional cardiopulmonary bypass (CPB) techniques were applied to these patients. Myocardial protection consisted of either crystalloid or blood cardioplegia associated with local hypothermia and moderate systemic hypothermia (32°C). In two patients deep hypothermia and circulatory arrest were used to replace the aortic arch. The CPB average time was 125 ± 41 minutes and aortic cross-clamping average time was 97 ± 34 minutes.

PERIOPERATIVE FINDINGS
The findings confirmed TEE data concerning the proliferative or destructive type of anatomic lesions. Intraoperative assessment of the mitral through the aortic valve was systematically performed. Vegetations were observed in 79 (77%), perforations in 89 (86%), and abscess or other periannular extension in 60 (58%) patients. Forty-two percent of these patients had isolated valvular damage without periannular extension (7% had isolated vegetations and 35% had cusp destruction by vegetation and perforation). Periannular extension lesions were found in 58% of the patients, including periannular abscesses (n = 40), left aortoventricular (n = 9), or aortomitral (n = 7) discontinuities, right aortoventricular fistulas (n = 1), aortopulmonary fistulas (n = 1), and false aneurysms (n = 2) (Table 1).

OPERATIVE PROCEDURES
The operative procedures are presented in Table 3. Resection of all infected valvular and perivalvular tissue was performed. Abscess cavities were opened and cleaned using iodine solution and treated with glutaraldehyde application. One hundred and four CAVH were inserted (aortic root replacement technique in 93 patients and the subcoronary technique in 11 patients). Thirty-eight associated procedures were performed, and included the following: 24 mitral valve repairs (13 for endocarditis lesions, 9 for nonendocarditis lesions), 5 mitral homografts were used for mitral (n = 3) and tricuspid (n = 2) endocarditis lesions, 3 tricuspid valve repairs (one for endocarditis lesions), 3 coronary bypass grafts, and 3 ascending or aortic arch replacements.

	Results

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In-Hospital Mortality and Morbidity
Five patients died (in-hospital mortality: 5%). Three deaths occurred in the PVE group (3 of 28 patients, 11%) and two in the NVE group (2 of 76 patients, 3%). Causes of early death were myocardial infarction (n = 2), myocardial failure (n = 2), and multiorgan failure (n = 1). In-hospital morbidity included the following: left ventricular dysfunction requiring inotropic drugs greater than 48 hours (n = 32), renal failure requiring hemodiafiltration (n = 11); pancreatitis and cholecystitis (n = 1), various transitory rhythm disturbances (n = 13), various conduction disturbances (n = 15), among them 3 third degree atrioventricular blocks requiring a permanent pacemaker, and reintervention for bleeding or pericardial effusion (n = 3) without lethal bleeding complication. No early valvular redo surgery was necessary. No early recurrent endocarditis (< 60 days) occurred. Ventilation support duration was less than 24 hours in 64 (62%) patients and intensive care stay was less than 48 hours in 66 (63%) patients. Forty-eight (46%) patients had an uneventful postoperative course; 66 patients presented with postoperative complications (hospital morbidity: 63%).

Follow-Up
Patient's data were obtained during medical consultation in our department or by phoning practitioners, cardiologists, or the patients themselves. No patients were lost from follow-up. Mean duration of follow-up was 61 ± 36 months (range, 6 to 136 months).

LATE MORTALITY
Nine patients died during follow-up. Two patients died from cardiac related death. One was a reoperative death. This patient, an intravenous drug abuser, died on postoperative month 16, following redo surgery for recurrent endocarditis. One other patient died from atrioventricular block on postoperative month 6. Other causes of death included: respiratory failure in a lupic patient (n = 1), bladder cancer (n = 1), leukemia (n = 1), HIV complications (n = 2), suicide (n = 1), and abdominal aortic aneurysm (n = 1). Overall cumulative survival, including in-hospital survival, was 93% at one year, 86% at five years, and 83% at ten years (Fig 1). At ten years, 93% of the patients were free from cardiac-related death.

View larger version (14K): [in this window] [in a new window]   Fig 1. Cumulative survival of all 104 patients after cryopreserved aortic viable homograft. Numbers of patients at risk are given at 20 month intervals above the abscissa. Cumulative survival, in-hospital mortality included. Solid line = overall survival; interrupted line = freedom from cardiac related death.

View larger version (14K): [in this window] [in a new window]   Fig 2. Cumulative freedom from valvular redo surgery. Numbers of patients at risk are given at 20 month intervals above the abscissa. Solid line = cumulative freedom from redo valvular surgery; interrupted line = cumulative freedom from redo valvular surgery for endocarditis.

	Comment

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Surgery is required in 50% of valvular endocarditis [20]. However, most of the time antibiotics allow a postponement of surgery until the sequelae phase. At the acute stage, patients often are in a precarious clinical status and anatomic lesions are particularly complex with the impairment of both the valve and the perivalvular area. In such an infected area, prosthesis implantation is technically difficult. Anatomic reconstruction has to be performed as well as infected tissues eradication, closing of the deterged cavities by a Dacron [1] or pericardial patch [2, 4], or even extraanatomic implantation of the prosthesis [3]. Except for a few recent publications underlining the importance of wide debridements at the cost of complex reconstructions [13, 14], high operative mortality rates have been reported, ranging from 10% to 30% and reaching more than 65% in cases of PVE [9–11] with high reoperation rates (3% to 30%) due to reinfection and periprosthetic dehiscence [9].

Human valvular substitutes are reported to have excellent hemodynamic performance, no need for lifelong anticoagulation, and a low risk of thromboembolism [5]. Cryopreserved aortic viable homograft has long been suggested as an alternative to prosthetic material to treat aortic endocarditis [5, 7, 8, 10]. The first rationale for use was an improved resistance to biological tissue infection compared with prosthetic materials, especially within the first six postoperative weeks [5, 8]. No early reinfection was observed in our series. Six patients, three of them drug abusers, experienced recurrent endocarditis between postoperative months 44 to 81. In three patients a second CAVH was performed. The second rationale is feasibility. The CAVH offers technical advantages due to its compliance and surrounding structures. The CAVH compliance compared to prosthesis stiffness reduces tear risk when sutures are placed within a fragile area as in the case of annular destruction (subannular implantation of the CAVH onto the septal muscle). Tissues adjoining the CAVH may be used to fill or patch structural defects [8]. Satisfactory results have been provided with aggressive eradication of infected tissues and prosthesis implantation, even if such an operation may be extremely difficult to achieve [13, 14]. But, debridement might be less aggressive when the surgeon needs tissue to implant a prosthetic valve. In fact, homograft could then be considered as an "easier" surgical technique and we have found the aortic root replacement particularly well-adapted. Aortic root replacement is a well-standardized technique. The operations in our series were performed without lethal bleeding complications and it is interesting to note that 31% (32 of 104) of these patients underwent a concomitant reconstructive mitral or tricuspid procedure, that should not discourage the homograft root reconstruction.

There is still concern regarding CAVH durability. [12, 15–19]. Durability analysis is complicated when different preservations are simultaneously presented in larger series [15–17]. Cryopreservation technique has improved the durability as compared to other techniques such as irradiation, fresh or freeze storage in antibiotic solution, and immediate transplantation [16]. The results we present are focused on CAVH, with a failure rate similar to previous reports [12, 15, 16, 18, 19]. Young recipient age, donor age, large aortic root diameter, geometric mismatch between homograft and native aortic root, previous xenograft valve implantation, and surgeon's learning curve notably with the free hand technique, have been previously reported as risk factors for homograft failure [15–18]. We have found no statistical difference in the risk factors for the six patients with structural failure in this series.

Should endocarditis management and surgical indication be modified considering the satisfactory results of CAVH? Hemodynamic instability, microbiology resistance, and anatomic lesions progression are traditional complications leading to early surgery. Heart failure most affects outcome, with a reported mortality rate of 17% to 33% compared to 6% to 11% without [5, 6, 11, 20]. Some microorganisms are known to require early surgery: fungi, staphylococcus aureus, streptococcus pneumoniae, ß-hemolytic streptococcus, gram negatives, and resistant microorganisms [11, 20]. They are usually involved in active aortic endocarditis including vegetations, cusp destruction, and periannular extensions. Aortic vegetations, especially when their diameter is superior to 10 mm, may be responsible for systemic embolization up to 65% involving the central nervous system with a major risk during the first two weeks after diagnosis [11, 20]. Aortic periannular extension can degenerate in abscesses, discontinuity, fistulas, aberrant communications and false aneurysm, increasing congestive heart failure, and mortality rate. Opportunity to avoid prosthesis and satisfactory results encountered with CAVH plead for an early surgical approach, which represents the only way to decrease these complications. Our policy is now to operate for aortic endocarditis earlier, before complications. Facing damage that would require surgery, we do not postpone surgery because of infection. We just wait for causative microorganism identification allowing for 2 or 4 days of adapted antibiotic therapy. The mean duration of antibiotics before surgery was 3.7 days for the last 30 patients.

The major limitation for CAVH use is the mismatch between availability and request. Pulmonary homografts have provided unsatisfactory results in aortic location [16, 21]. Pulmonary autograft is a more technically demanding double orifice procedure that requires an opening of a noninfected orifice in an infected area. We reserve this technique for young patients because of the decreased durability of CAVH in this patient group [16, 22]. For adult patients, stentless valves, notably those without any Dacron, represent an interesting alternative in case of CAVH unavailability.

Cryopreserved aortic viable homografts are perfectly suited to treat complex active aortic endocarditis. The possibility of avoiding prosthetic material represents a rationale to surgically treat active endocarditis more rapidly.

	References

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