Identification of latent classes of CAV trajectories after heart transplantation and their determinants

Background Cardiac allograft vasculopathy (CAV) remains a major issue associated with increased mortality after heart transplantation (HTx). Prototypes of CAV trajectories including dynamics of progression and associated determinants have not been assessed. Purpose To identify distinct profiles of CAV trajectory following HTx and their determinants. Methods We performed a retrospective multicenter observational study. We included all consecutive patients transplanted between 2004 and 2011 who had at least 2 coronary angiograms during follow-up. We performed an extensive evaluation of potential risk factors that might be associated with CAV. A semi-parametric mixture model was used to identify distinct trajectories of CAV progression from year 1 to year 8 post-transplantation. Multivariable logistic regression model was used to determine risk factors associated with each trajectory. Results Four hundred and forty-six patients met the inclusion criteria. Median follow-up time post transplant was 6.3 years. Three distinct profiles of CAV trajectories were identified: #1-non-progressors ( n  = 280, 62.8%), #2- slow progressors ( n  = 118, 26.5%) and #3- rapid progressors ( n  = 48, 10.8%). Factors independently associated with CAV trajectory #2 were donor age, donor male gender, tobacco consumption of the donor and pre-HTx recipient dyslipidemia. In addition to the previous factors, ischemic etiology of heart failure and the presence of circulating C1q-binding DSA were independent risk factors for CAV trajectory #3. Conclusion In a large and extensively phenotyped cohort of heart transplant recipients, we identified 3 distinct prototypes of CAV trajectories. In addition to traditional cardiovascular risk factors, the presence C1q-binding donor-specific anti-HLA antibodies was associated with an acceleration of CAV.