Increasing Risk of Post-Heart Transplant Hospitalizations for Infection: An Analysis of Recent Trends

S. Feng¹, A. Zhou¹, A. Akbar¹, J. Ruck¹, A. Kilic^2
1Divison of Cardiothoracic Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Baltimore, Maryland ²The Johns Hopkins Hospital, Baltimore, Maryland

Purpose: Infection contributes significantly to morbidity and mortality post-heart transplantation (HT).1 Recent trends in post-HT infection have not been elucidated. Viral diseases can affect transplant recipient immune function.2 Thus, we examined trends in hospitalizations for infection in the first year after HT by recent time eras, considering pre- and post-COVID-19 contexts.

Methods: We identified all adult HT recipients in the U.S. from 10/18/2018 to 06/30/2023 in the United Network for Organ Sharing database. We categorized transplants into 3 eras to account for both the October 2018 allocation policy change and the COVID-19 pandemic: 10/2018-03/2020 (Era 1), 03/2020-03/2022 (Era 2), and post-03/2022 (Era 3). Baseline characteristics were compared using descriptive statistics. Post-transplant outcomes and hospitalizations for infection in the first year post-HT were compared using both univariate analysis and multivariable logistic regression. Covariates included in the final multivariable models were selected according to clinical relevance and by significance at a level of p< 0.1 on univariate analysis. Covariates included: era, recipient age, recipient sex, recipient race, recipient body mass index, recipient diabetes, recipient ECMO, recipient ventilator, recipient blood group, recipient days on waitlist, donor age, donor sex, donor race, and induction therapy (antithymocyte globulins and basiliximab).

Results: Of 13,663 patients who received HT (median age=57, male=72.9%), 3,645 patients were transplanted during Era 1 (October 18, 2018-March 2020), 5,658 during Era 2 (March 2020-March 2022), and 4,360 during Era 3 (March 2022-June 2023). Over the study period, pre-transplant ECMO increased from 4.8% (n=175) to 6.6% (n=287) (p < 0.001). Median waitlist days decreased from 42 (10-1298) to 25 (9-110) days (p < 0.001). Additionally, antithymocyte use decreased from 1.9% (n=70) to 1.2% (n=54), while basiliximab use increased from 25.3% (n=922) to 26.0% (n=1,135) (p < 0.001). Compared to Era 1, odds of acute rejection were lower in subsequent eras (Era 2: aOR=0.88, 95% CI=0.79-0.98, p=0.017; Era 3: aOR=0.69, 95% CI=0.61-0.78, p< 0.001). While rates of both post-transplant stroke and dialysis increased over the study period (p < 0.001), these differences were no longer significant after multivariable adjustment. Hospitalization for infection in the first year post-HT was 2.9% for patients transplanted during Era 1 (N=3,645), 5.4% during Era 2 (N=5,658), and 11.6% during Era 3 (N=4,360; p< 0.001). Compared to patients transplanted during Era 1, patients transplanted during Era 2 (aOR=1.91, 95%CI=1.51, 2.41) and Era 3 (aOR=4.37, 95%CI=3.30, 5.78) were more likely to be hospitalized for infection in their first year after HT.

Conclusion: Compared to patients who received HT between October 2018 and March 2020, odds of hospitalization for infection in the first year post-HT was 1.91 times as high for patients transplanted between March 2020-March 2022, and 4.37 times as high for patients transplanted post-March 2022. Improving our understanding of this alarming rise in post-transplant infections will be crucial to improving patient care and outcomes for HT recipients. In particular, further investigation is warranted to better understand the potential mechanisms underlying these trends, including the possibility of persistent immune dysfunction and suppression exacerbated by environmental factors such as COVID-19.

Identify the source of the funding for this research project: N/A