Identification and characterization of trajectories of cardiac allograft vasculopathy after heart transplantation

5/4/2020

Every year, tens of thousands of deaths are due to end-stage heart failure in Europe and in the US combined. Heart transplantation is the ultimate treatment, but its number is dramatically limited due to the shortage of organs in those countries.

In the same time, the chances of survival beyond one year after transplantation have remained unchanged in recent years, despite significant progress in immunosuppressive therapy and patient care.

One of the most common reasons for long-term graft failure and patient death is an accelerated form of coronary artery disease called cardiac allograft vasculopathy. It is a frequent complication that affects up to half of patients within 10 years following heart transplantation. Yet, until now, little has been known about the different evolutive profiles of cardiac allograft vasculopathy and their risk factors.

An original long-term study at population level on heart transplantation

The Paris Transplant Group, together with researchers from the University Hospitals Leuven and the Cedars-Sinai Medical Center, monitored 1,300+ patients over ten years after heart transplantation. Their research led to the characterisation of different profiles of vasculopathy progression. They just published the results of their study in an article entitled “Identification and characterization of trajectories of cardiac allograft vasculopathy after heart transplantation” in the Circulation journal.

This is one of the largest studies in the field of heart transplantation with a total of 1,301 patients included and 4,710 coronary angiograms analyzed. For the first time, an integrative approach was used to analyze a comprehensive set of clinical, functional, histological and immunological data.

Characterization of 4 trajectories of long-term cardiac allograft vasculopathy progressioN

By applying an unsupervised statistical method in a large European cohort, the researchers were able to identify four distinct patterns of progression of allograft cardiac vasculopathy after the heart transplant (see figure below) that reflect distinct functional, clinical, immunologic, histologic patterns. The four cardiac allograft vasculopathy trajectories showed a gradient of mortality risks

These cardiac allograft vasculopathy trajectories were validated in an independent North American cohort. The multiple tests and validation processes showed that the identified trajectories and associated variables could be generalized and transportable across different medical centres on different continents.

From this analysis, six candidate variables independently associated with cardiac allograft vasculopathy were identified: donor age, donor gender, donor tobacco consumption, recipient post-transplant dyslipidemia, the presence of anti-HLA donor-specific antibodies and episode of acute cellular rejection during the first year post-transplantation.

Towards individualized monitoring of heart transplant patient

This study has led to an easy-to-use tool for stratifying patient risk for the progression of cardiac allograft vasculopathy over time after heart transplantation. The tool is available online.

Predictive trajectory-based patient monitoring could allow individualization of patient follow-up procedures and medical therapies, thus reducing unnecessary angiograms in low-risk patients and intensifying treatment and angiogram monitoring in high-risk patients. In addition, the patient trajectory assessment that can be performed at an early stage after transplantation may inform the design and optimize endpoint definition of next generation clinical trials.