Clinicopathological correlations in heart transplantation recipients complicated by death or re-transplantation

Michelle M McDonald; Maks Mihalj; Bihong Zhao; Sriram Nathan; Stanislava Matejin; Giulia Ottaviani; Mateja K Jezovnik; Rajko Radovancevic; Biswajit Kar; Igor D Gregoric; L Maximilian Buja

doi:10.3389/fcvm.2022.1014796

Clinicopathological correlations in heart transplantation recipients complicated by death or re-transplantation

Front Cardiovasc Med. 2022 Nov 3:9:1014796. doi: 10.3389/fcvm.2022.1014796. eCollection 2022.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX, United States.
² Department of Advanced Cardiopulmonary Therapies and Transplantation, University of Texas Health Science Center at Houston, Houston, TX, United States.
³ Department of Cardiac Surgery, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Cardiovascular Pathology, Lino Rossi Research Center, Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.

Abstract

Purpose: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.

Methodology and study design: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared.

Results: We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR ≥ 1) (32% vs. 12%, P = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR ≥ 2R) (32% vs. 40%, P = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, P = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711-1,664], P < 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, P = 0.020). No difference was observed in other outcomes.

Conclusion: In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT.

Keywords: C4d; acute myocardial injury; cardiac allograft vasculopathy; endomyocardial biopsy; heart transplantation; primary graft dysfunction; rejection.