The "no Biopsy Approach" for Heart Transplantation Follow-up

Completed

• Conditions: Cardiac Transplant Rejection
• Interventions: Diagnostic Test: systematic endomyocardial biopsy.

• Registration Number: NCT03959579
• Lead Sponsor: Centre Chirurgical Marie Lannelongue

Brief Summary

Pathological analysis is the gold standard for diagnosis of acute allograft rejection after heart transplantation (HTx). This method requires repeated endomyocardial biopsies during the first post-operative year. However the sensitivity of endomyocardial biopsy (EMB) is not perfect and can be associated with major complications including fatal tamponade. Moreover, repeated biopsies are associated with reduced quality of life for HTx recipients.

Since almost 20 years, the investigators do not perform routinely EMB for acute rejection screening. Early left ventricular diastolic dysfunction was investigated according to a standardized protocol. The investigators sought to analyze the long-term post-transplant outcomes without systematic EMB. The investigators hypothesize that exclusive echographic screening was not associated with impaired outcomes.

Detailed Description

Demographic characteristics of heart transplant recipients and organ donors were prospectively collected in a local database. All HTx successively performed in the Hospital Marie Lannelongue from 1990 to 2016 were included. From 1990 to 1997, both EMB and cardiac echo were routinely performed at each medical follow-up date. After 1997, only cardiac echo was used to detect early acute allograft rejection. The investigators collected the results of all EMB and synchronous cardiac echo in patients transplanted between 1990 and 1997 (group A, validation cohort), and clinical events and long-term survival in patients transplanted from 1998 to 2016 (group B, standardization cohort). For our purpose, the investigators graded the histological patterns of acute cardiac rejection according to the 1990 international classification. Cardiac echo assessment included the isovolumic relaxation time, E-wave velocity and E/A ratio. Impaired left ventricular relaxation was consistent with acute cardiac rejection.

The investigators therefore analyzed the rate of positive and negative EMB during the first post-transplant year and compared these results to the synchronous cardiac echo report in group A. Sensibility and specificity of cardiac echo to detect acute cardiac rejection were calculated. The rate of acute cardiac rejection during the first year was collected in group B and compared to group A. Finally, long-term survival was analyzed according to the Kaplan-Meier approach and compared between group A and B (log-rank test). The investigators hypothesize that the participant will not observe any differences between groups considering the rate of acute cardiac rejection during the first year. In addition, the investigators do not expect to find any significant difference in long-term survival between the two cohorts. These findings may have a major impact on HTx follow-up since systematic EMB could be replaced by a standardized cardiac echo protocol focusing on left ventricular wall relaxation. EMB should therefore only be indicated in case of acute allograft dysfunction without evidence of rejection on conventional cardiac echo.

Study Timeline

• Study Start: 2017-11-22
• Primary Completion: 2018-03-31
• Study Completion: 2018-03-31
• Status Verified: 2018-05
• Study First Submitted: 2018-05-04
• Study First Submitted QC: 2019-05-21
• Last Update Submitted: 2019-05-21
• Study First Posted: 2019-05-22
• Last Update Posted: 2019-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 269

Inclusion Criteria

• All heart transplant patients, including heart / liver and heart / kidney, and followed at Marie Lannelongue Hospital
• Transplantations carried out between 01/01/1990 and 31/12/2006
• Major and minor patients

Exclusion Criteria

• Patient with missing test data (cardiac ultrasound or endomyocardial biopsy)
• Patient who did not simultaneously benefit from cardiac ultrasound and endomyocardial biopsy (Delayed period of +/- 1 days)
• Patient who had an endomyocardial biopsy without cardiac ultrasound the day before or the day after endomyocardial biopsy.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1st cohort = "derivation cohort":	systematic endomyocardial biopsy.	1st cohort = "derivation cohort": 1990-1998: cardiac echo + simultaneous systematic endomyocardial biopsy

Primary Outcome Measures

Name	Time	Method
Long-term survival	15 years	Survival of patients

Secondary Outcome Measures

Name	Time	Method
Positive Predictive Value	15 years	Positive Predictive Value of Cardiac Ultrasound to Diagnose Acute Heart Releases in the 1st Group
Negative Predictive Value	15 years	Negative Predictive Value of Cardiac Ultrasound to Diagnose Acute Heart Releases in the 1st Group
Sensitivity	15 years	Sensitivity of Cardiac Ultrasound to Diagnose Acute Heart Releases in the 1st Group
Specificity	15 years	Specificity of Cardiac Ultrasound to Diagnose Acute Heart Releases in the 1st Group

Trial Locations

Locations (1)

Hopital Marie Lannelongue; 🇫🇷 Le Plessis-Robinson, France