Development of an International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation

Abstract

<h3>Purpose</h3> Primary Graft Dysfunction (PGD) is a leading cause of short-term mortality after heart transplantation (HT). Available registries lack data to identify PGD based on post-HT hemodynamics and mechanical circulatory support (MCS). Herein, we describe the development of a multicenter International Consortium on PGD: a registry designed to quantify the incidence, risk factors, and impact of PGD, in order to develop contemporary risk prediction models. <h3>Methods</h3> We are currently collecting data from 10 participating sites in Europe and North America which will include clinical data from an estimated 3,826 HT recipients (Table 1). We defined PGD using the ISHLT 2014 consensus criteria. Our complete consortium will include data on baseline donors and recipients demographics, pre and post-HT hemodynamics, and the type and duration of MCS after HT. We will use regression models and supervised machine learning (ML) algorithms to develop risk prediction models that reflect the contemporary landscape of HT. <h3>Endpoints</h3> To date, we have collected preliminary data on 2,178 single-organ HT recipients between 2010 - 2020 (57% of the anticipated final sample size). Our consortium cohort consists of patients with age of 54 ± 12 years, of whom 24.7% (n=537) are female. Pre-transplant MCS included IABP in 3.6% (n=80), ECMO in 1.4% (n=30), and durable LVAD in 8.3% (n=181). Donor age was 37 ± 13 years and ischemic time was 3.4 ± 1.0 hours. A total of 167 (7.7%) recipients met criteria for severe PGD and 76 (6.5%) for moderate PGD. One-year survival was 67% (95% CI 59 - 74%) and 93% (95% CI 92 - 94%) in patients with and without severe PGD, respectively. We aim to develop contemporary tools for risk stratification of HT recipients for incident PGD. Our multicenter, international consortium allows for comprehensive phenotyping of HT recipients based upon a standardized definition of PGD to accurately understand PGD incidence, risk factors, and outcomes in the era of MCS. <h3>Interim Results</h3> To date, we have collected 106 variables on 2,476 single-organ HT recipients from 2010 to 2020 (Figure 1A). Mean age of cohort is 53.9 ± 12.3 years; 25% female, 330 recipients from Canada, 518 from Europe, and 1628 from the US. Pre-transplant MCS included IABP in 8.4% (n=207), ECMO in 1.3% (n=33), and durable LVAD in 32.1% (n=795) (Figure 1B). Average donor age was 36.4 ± 13.0 years with mean ischemic time 3.4 ± 1.1 hours. A total of 214 (8.6%) of recipients met criteria for severe PGD, requiring VA-ECMO (n=186), RVAD (n=28), or both (n=3). Among 1811 patients with adequate follow up data, 1-year survival was 78% (95% CI 72% – 83%) in patients with severe PGD, and 95% (95% CI 94% – 96%) in those without severe PGD (Figure 1C). The previously-published RADIAL PGD risk score performed poorly in our cohort, with an AUC of 0.50 for severe PGD(Figure 1D).