Clinical trial NCT03959579: The "no Biopsy Approach" for Heart Transplantation Follow-up
Official title: Long-term Outcomes After Non-invasive Assessment of Acute Cardiac Rejection in Heart Transplantation : the Marie Lannelongue Hospital Experience
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Transplant Rejection
Lead sponsor: Centre Chirurgical Marie Lannelongue
Sponsor class: OTHER
First posted: 2019-05-22
Enrollment: 269
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 269 patients (alive and deceased) patients transplanted between 1990 and 1998 and 1999 and 2016

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Long-term survival
timeFrame: 15 years
Secondary outcomes:
measure: Sensitivity
timeFrame: 15 years
measure: Specificity
timeFrame: 15 years
measure: Positive Predictive Value
timeFrame: 15 years
measure: Negative Predictive Value
timeFrame: 15 years
Other outcomes:
measure: Incidence of long-term complications
timeFrame: 15 years
Locations:
city: Le Plessis-Robinson
country: France
facility: Hopital Marie Lannelongue
Study officials:
affiliation: Marie Lannelongue Hospital
name: Julien Guihaire, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: