Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation

Study Overview
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Brief Summary
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This project aims: i) to identify Cardiac Allograft Vasculopathy (CAV) trajectories after heat transplantation using latent class mixed modeling, ii) to characterize the global and specific determinants of different trajectories and iii) to provide an easily accessible tool to project individual probability of CAV trajectory belonging.

Detailed Description
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Background: Cardiac Allograft Vasculopathy (CAV) is the third cause of late mortality and the leading cause of late allograft dysfunction. The field of heart transplantation currently lacks longitudinal description of CAV profiles. Identifying relevant CAV trajectories, or evolution profiles, and their respective determinants is an unmet clinical need. CAV trajectories requires an additional level of understanding and characterization over the current paradigm. Understanding the mechanisms and clinical factors involved in the development of CAV will be useful to provide a more nuanced picture of disease progression, which may ultimately contribute to risk stratification and ultimately guiding the care of HTx patients. Main Outcome(s) and Measure(s): Identification of CAV trajectories after transplantation using an unsupervised latent class mixed modeling. CAV angiograms were recorded per center protocol for all patients after transplantation. CAV was graded according to the current ISHLT classification as CAV 0 (not significant), 1 (mild), 2 (moderate) and 3 (severe). Determination of clinical, functional, structural, immunological factors associated with the trajectories. In the derivation cohort, the associations between CAV trajectories and clinical, histological, functional, and immunological parameters at the time of transplantation, during the first year and at one-year post-transplant were assessed using multinomial logistic regression.

Official Title
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Multicenter International Observational Study to Identify Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and Their Specific Determinants

Conditions
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Heart Transplantation, Allograft Arteriopathy

Intervention / Treatment
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* Other: Latent class mixed modeling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart recipient with at least two coronary angiograms after heart transplantation, Heart recipient over 18 years of age. Exclusion Criteria: Patient with < 2 coronary angiograms during follow-up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Latent class mixed modeling|To identify CAV trajectories after heart transplantation using a contemporary unsupervised trajectory-based approach known as latent class mixed modeling|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of trajectories of Cardiac Allograft Vasculopathy (CAV) | Identification of different evolutive profiles of CAV using latent classes mixed models. Each coronary angiogram was graded from 0 (no CAV) to 3 (severe CAV) according to ISHLT classification. | 10 years post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of the specific determinants of CAV trajectories | Identification of immune and non-immune determinants using multivariable multinomial logistic regression. | From transplantation to 1-year post-transplant | 
| Early prediction of CAV trajectories | Probability of belonging to each trajectory according to the baseline angiogram and independent risk factors for CAV | 10 years post-transplant | 
| Patients and allograft survival probability according the CAV trajectory | Comparison of prognosis according the CAV trajectory | 10 years post-transplant |