Infective Endocarditis Surgery Using Conventional Prosthetic Valves Versus Cryopreserved Aortic Homograft

• Conditions: Infective Endocarditis; Heart Failure
• Interventions: Procedure: Cryopreserved Aortic Homograft; Procedure: Stented/Non stented xenograft; Procedure: Mechanical prostheses

• Registration Number: NCT05253469
• Lead Sponsor: Centre Cardiologique du Nord

Brief Summary

: Evidence suggested that autologous or allogeneic tissue is more suitable to synthetic material in an infected field. Given the unwillingness of some surgeons to use artificial foreign materials, such as conventional mechanical or stent xenograft valve prostheses, cryopreserved aortic homografts (CAH) have been recommended revealing favorable outcomes in aortic valve endocarditis (AVE) surgery (1-5). This aspect is even more evident in cases involving prosthetic valve endocarditis (PVE) and other complex and aggressive lesions involving the aortic root and intervalvular fibrosa with abscess formation. However, most of these reports are fixed on single-arm observational studies without comparing CAH with conventional prostheses.

The key question of this study is to establish the difference in treatment failure (death, recurrent aortic valve regurgitation and reoperation), all-cause and cause-specific (cardiac vs noncardiac) mortality, hospitalizations for heart failure during follow-up (structural/non structural valve deterioration, thromboembolism and recurrent endocarditis) in patients who received the CAH vs conventional mechanical or stent xenograft valve prostheses for aortic valve replacement (AVR) secondary to infective endocarditis (IE)

Detailed Description

The target population enrolled in the study includes patients with aortic-valve endocarditis at risk of embolization, heart failure and uncontrolled infection undergoing AVR with the use of CAH or conventional mechanical or stent xenograft valve prostheses. Individuals were adequately treated per applicable standards, including for the treatment of infection, LV dysfunction and heart failure. Patients enrolled in the studies were NYHA functional class II, III, or outpatient NYHA IV.

Three groups of patients are included in the study. Patients who were managed with CAH, patients who received AVR with conventional stented xenograft and recipients of AVR undergoing surgery with the use of mechanical prostheses.

Study Timeline

• Study Start: 2022-02-14
• Study First Submitted: 2022-02-14
• Study First Submitted QC: 2022-02-14
• Study First Posted: 2022-02-23
• Status Verified: 2024-01
• Last Update Submitted: 2024-12-21
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-03-31
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 800

Inclusion Criteria

• Duke Criteria
• Uncontrolled Infection Local abscess Large vegetation False aneurysm, Fistula, Dehiscence of PV
• Embolism Large vegetation >10mm, persistent infection
• Heart Failure Involvement of aortic root, intervalvular fibrosa, pulmonary edema, cardiogenic shock

Exclusion Criteria :

• Pediatric
• Any echocardiographic evidence of absence of IE

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Stented/Non stented xenograft	Stented/Non stented xenograft	Stented/Non stented xenograft may be inserted using separate or continuos stich with or without teflon pledget. The use of biological valves increased from 57% to 67% for primary the operation during which the use of mechanical valves decreased from 30% to 24%. For reoperations, the use of biologic valves increased from 38% to 52% compared to the warning use of mechanical valves from 20% to 17%. A homograft was used in only 2.5% of valve replacements, while a biological valve was used in 68.7% of the cases. This trend is reversed both in NVE and PVE the aortic root was involved (6). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional stented /non stented xenograft are used in combination with synthetic patch for both NVE and PVE.
Mechanical valve prostheses	Cryopreserved Aortic Homograft	Mechanical prostheses may be inserted using separate or continuos stich with or without teflon pledget. Prior to 2000, mechanical valves were used in 50% of patients compared to 14% since 2009. Analysis of the STS Database (6) showed that from 2005 to 2011 a progressive shift in favour of biological valves both as the primary operation (NVE) (73%) and in the reoperation (PVE) (27%) compared to mechanical prosthesis. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. aortic root and intervalvular fibrosa). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional mechanical prostheses are used in combination with synthetic patch for both NVE and PVE
Cryopreserved Aortic Homograft	Cryopreserved Aortic Homograft	Include patients who received CAH for native (NVE) or prosthetic valve endocarditis (PVE). The CAH are implanted using miniroot procedure. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. Aortic root and intervalvular fibrosa). Use of homograft in first time aortic valve replacement for IE decreased over time (9,4% to 5,6%) and in reoperation (37,5% to 28,5%) in a report from STS database between 2005-2011 (6). Nevertheless, the homograft was used more often in reoperations than in primary interventions (32.2% vs 7.0%, p \< 0.0001) in both valve replacements (14,6%) and for root replacements (53,2%) (6).
Cryopreserved Aortic Homograft	Mechanical prostheses	Include patients who received CAH for native (NVE) or prosthetic valve endocarditis (PVE). The CAH are implanted using miniroot procedure. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. Aortic root and intervalvular fibrosa). Use of homograft in first time aortic valve replacement for IE decreased over time (9,4% to 5,6%) and in reoperation (37,5% to 28,5%) in a report from STS database between 2005-2011 (6). Nevertheless, the homograft was used more often in reoperations than in primary interventions (32.2% vs 7.0%, p \< 0.0001) in both valve replacements (14,6%) and for root replacements (53,2%) (6).
Stented/Non stented xenograft	Cryopreserved Aortic Homograft	Stented/Non stented xenograft may be inserted using separate or continuos stich with or without teflon pledget. The use of biological valves increased from 57% to 67% for primary the operation during which the use of mechanical valves decreased from 30% to 24%. For reoperations, the use of biologic valves increased from 38% to 52% compared to the warning use of mechanical valves from 20% to 17%. A homograft was used in only 2.5% of valve replacements, while a biological valve was used in 68.7% of the cases. This trend is reversed both in NVE and PVE the aortic root was involved (6). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional stented /non stented xenograft are used in combination with synthetic patch for both NVE and PVE.
Mechanical valve prostheses	Mechanical prostheses	Mechanical prostheses may be inserted using separate or continuos stich with or without teflon pledget. Prior to 2000, mechanical valves were used in 50% of patients compared to 14% since 2009. Analysis of the STS Database (6) showed that from 2005 to 2011 a progressive shift in favour of biological valves both as the primary operation (NVE) (73%) and in the reoperation (PVE) (27%) compared to mechanical prosthesis. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. aortic root and intervalvular fibrosa). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional mechanical prostheses are used in combination with synthetic patch for both NVE and PVE
Cryopreserved Aortic Homograft	Stented/Non stented xenograft	Include patients who received CAH for native (NVE) or prosthetic valve endocarditis (PVE). The CAH are implanted using miniroot procedure. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. Aortic root and intervalvular fibrosa). Use of homograft in first time aortic valve replacement for IE decreased over time (9,4% to 5,6%) and in reoperation (37,5% to 28,5%) in a report from STS database between 2005-2011 (6). Nevertheless, the homograft was used more often in reoperations than in primary interventions (32.2% vs 7.0%, p \< 0.0001) in both valve replacements (14,6%) and for root replacements (53,2%) (6).
Stented/Non stented xenograft	Mechanical prostheses	Stented/Non stented xenograft may be inserted using separate or continuos stich with or without teflon pledget. The use of biological valves increased from 57% to 67% for primary the operation during which the use of mechanical valves decreased from 30% to 24%. For reoperations, the use of biologic valves increased from 38% to 52% compared to the warning use of mechanical valves from 20% to 17%. A homograft was used in only 2.5% of valve replacements, while a biological valve was used in 68.7% of the cases. This trend is reversed both in NVE and PVE the aortic root was involved (6). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional stented /non stented xenograft are used in combination with synthetic patch for both NVE and PVE.
Mechanical valve prostheses	Stented/Non stented xenograft	Mechanical prostheses may be inserted using separate or continuos stich with or without teflon pledget. Prior to 2000, mechanical valves were used in 50% of patients compared to 14% since 2009. Analysis of the STS Database (6) showed that from 2005 to 2011 a progressive shift in favour of biological valves both as the primary operation (NVE) (73%) and in the reoperation (PVE) (27%) compared to mechanical prosthesis. For extended aortic valve infection, aortic root replacement and reconstruction of regional contiguity is the recommended approach. Complicated aortic IE may present with destruction of a large portion of the aortic annulus, annular abscess and colonization of infected foci in contiguous cardiac structures (eg. aortic root and intervalvular fibrosa). In the presence of peri-annular abscess formation and mitro-aortic discontinuity, conventional mechanical prostheses are used in combination with synthetic patch for both NVE and PVE

Primary Outcome Measures

Name	Time	Method
Treatment failure	10 years	The primary end point of the study is the degree of treatment failure as assessed by death, recurrent aortic valve regurgitation and reoperation

Secondary Outcome Measures

Name	Time	Method
Overall Mortality	10 years	The secondary endpoint of the study is the evaluation of overall mortality
Cardiac Death	10 years	The secondary endpoint of the study is the evaluation of cardiac death
Hospitalizations for Heart Failure (HF)	10 years	The secondary endpoint of the study is the evaluation of hospedalization rates for heart failure valve due to structural/non structural valve deterioration, thromboembolism and recurrent endocarditis
Echocardiographic Parameter Changes (recurrence)	10 years	Recurrent moderate-to-severe aortic regurgitation after intervention
Echocardiographic Parameter Changes (LVEDD)	10 years	Changes from baseline Left Ventricular End Diastolic Diameter
Echocardiographic Parameter Changes (Aortic Root diameter)	10 years	Changes from baseline aortic root diameter
Echocardiographic Parameter Changes (LVEF)	10 years	Changes from baseline parameters including left ventricular ejection fraction
Non Cardiac Death	10 years	The secondary endpoint of the study is the evaluation of non cardiac death
Major Adverse Cardiac or Cerebrovascular Events (MACCE)	10 years	Composite of major adverse cardiac or cerebrovascular events (rate of death, stroke, subsequent mitral valve surgery, hospitalization for heart failure, or an increase in New York Heart Association class higher than one), serious adverse events, recurrent aortic regurgitation, quality of life, and rehospitalization.

Trial Locations

Locations (1)

Francesco Nappi; 🇫🇷 Saint Denis, France