Incidence of Acute Rejection Compared With Endomyocardial Biopsy Complications for Heart Transplant Patients in the Contemporary Era.

BACKGROUND: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the incidence of treated AR compared with EMB complications has not been compared in the contemporary era (2010-current). METHODS: The authors retrospectively analyzed 2769 EMBs obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for-cause indication, recipient and donor characteristics, EMB procedural data and pathological grades, treatment for AR, and clinical outcomes. RESULTS: The overall EMB complications rate was 1.6%. EMBs performed within 1 mo after HTx compared with after 1 mo from HTx showed significantly increased complications (OR, 12.74, P < 0.001). The treated AR rate was 14.2% in the for-cause EMBs and 1.2% in the surveillance EMBs. We found the incidence of AR versus EMB complications was significantly lower in the surveillance compared with the for-cause EMB group (OR, 0.05, P < 0.001). We also found the incidence of EMB complications was higher than treated AR in surveillance EMBs. CONCLUSIONS: The yield of surveillance EMBs has declined in the contemporary era, with a higher incidence of EMB complications compared with detected AR. The risk of EMB complications was highest within 1 mo after HTx. Surveillance EMB protocols in the contemporary era may need to be reevaluated.

Antibody Mediated Rejection is not Associated with Worse Survival in Adherent Heart Transplant Patients in the Contemporary Era.

Background: C4d immunostaining of surveillance endomyocardial biopsies (EMB) and testing for donor specific antibodies (DSA) are routinely performed in the first year of heart transplantation (HTx) in adult patients. C4d and DSA positivity have not been evaluated together with respect to clinical outcomes in the contemporary era (2010-current). Methods: This was a single center, retrospective study of consecutive EMBs performed between November 2010 and April 2023. The primary objective was to determine whether history of C4d and/or DSA positivity could predict death, cardiac death, or retransplant. Secondary analyses included cardiac allograft dysfunction and cardiac allograft vasculopathy. Cox proportional hazards models were used for single predictor and multipredictor analyses. Results: A total of 6,033 EMBs from 519 HTx patients were reviewed for the study. There was no significant difference (p = 0.110) in all-cause mortality or cardiac retransplant between four groups: C4d+/DSA+, C4d+/DSA-, C4d-/DSA+, and C4d-/DSA-. The risk for cardiac mortality or retransplant was significantly higher in C4d+/DSA+ versus C4d-/DSA- patients (HR = 4.73; pc = 0.042) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc = 1.000). Similarly, the risk for cardiac allograft dysfunction was significantly higher in C4d+/DSA+ versus C4d-/DSA- patients (HR 3.26; pc = 0.001) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc = 1.000). Accounting for nonadherence, C4d/DSA status continued to predict cardiac allograft dysfunction but no longer predicted cardiac death or retransplant. Conclusions: Medically adherent C4d+/DSA+ HTx patients show significantly greater risk for cardiac allograft dysfunction but not cardiac mortality or retransplant. In contrast, C4d+/DSA- patients represent a new immunopathologic group with a clinical course similar to that of HTx patients without antibody mediated rejection.

Benefit versus Risk of Endomyocardial Biopsy for Heart Transplant Patients in the Contemporary Era.

Background: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the benefit of diagnosing and treating AR compared to the risk of EMB complications has not been compared in the contemporary era (2010-current). Methods: The authors retrospectively analyzed 2,769 EMB obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for cause indication, recipient and donor characteristics, EMB procedural data and pathologic grades, treatment for AR, and clinical outcomes. Results: The overall EMB complication rate was 1.6%. EMBs performed within 1 month after HTx compared to after 1 month from HTx showed significantly increased complications (OR = 12.74, p < 0.001). The treated AR rate was 14.2% in the for cause EMBs and 1.2% in the surveillance EMBs. We found the benefit/risk ratio was significantly lower in the surveillance compared to the for cause EMB group (OR = 0.05, p < 0.001). We also found the benefit to be lower than risk in surveillance EMBs. Conclusions: The yield of surveillance EMBs has declined, while for cause EMBs continued to demonstrate a high benefit/risk ratio. The risk of EMB complications was highest within 1 month after HTx. Surveillance EMB protocols in the contemporary era may need to be re-evaluated.