Journal of Heart and Lung Transplantation最新文献

Background: Although recommended in International Society for Heart and Lung Transplantation (ISHLT) guidelines, transition to mammalian targets of rapamycin (mTOR) inhibitors in heart transplant recipients is not routinely performed, in part due to perceived risk of rejection. This study sought to evaluate the incidence and risk factors for biopsy-proven, clinically relevant rejection following conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) immunosuppression.

Methods: A single center retrospective study was conducted of all consecutive adult patients who underwent orthotopic heart transplantation (OHT) and CNI-free SRL conversion from January 1999 to January 2023. All post-OHT biopsy data were obtained and graded per ISHLT criteria (antibody-mediated rejection [pAMR] or acute cellular rejection [ACR]). The primary endpoint was early rejection, defined as grade 2R ACR, pAMR 1, or greater, within 6 months after conversion.

Results: 317 patients (72% male, mean age 51.5 ± 12.6 years) were included. Median time to SRL conversion following OHT was 0.76 years (IQR 0.49, 1.42). Median time from conversion to rejection was 0.51 years (IQR 0.31, 1.05). 38 patients (12%) experienced early rejection. Following multivariate analysis, both timing to SRL conversion following OHT (OR 0.94 per month, 95% CI: 0.89-0.99, p-value = 0.0054) and age at transplantation (OR 0.96, 95% CI: 0.93-0.99, p-value = 0.0071) were independently associated with early rejection. Rejection following SRL conversion was not associated with increased risk of cardiac allograft vasculopathy (CAV) grade 2-3.

Conclusions: In a CNI-free SRL conversion protocol, both earlier SRL conversion following OHT and younger age at transplant are independently associated with early rejection, but rejection is not associated with a net increased risk of prognostically important CAV. Individualization of transition is necessary to mitigate risk, and these findings may aid in improvement of future conversion protocols.

Background: Cardiac allograft vasculopathy (CAV) results in impaired blood flow in both epicardial vessels and the microvasculature and is a leading cause of poor outcomes in heart transplant (HT) recipients. Most patients have mild (International Society for Heart and Lung Transplantation [ISHLT] CAV 1) disease. This study examined outcomes among those with ISHLT CAV 1 and investigated the value of physiologic assessment via cardiac positron emission tomography/computed tomography (PET/CT) for added risk stratification.

Methods: CAV was graded using ISHLT criteria. Those with CAV 1 were further subgrouped into CAV 1a (maximal lesion <30% stenosis) or CAV 1b (maximal lesion ≥30% stenosis).

Results: 299 HT recipients underwent invasive coronary angiography for CAV assessment with a median follow-up of 4.7 years. ISHLT CAV 1 was associated with a 2.9-fold risk of death/retransplantation compared to ISHLT CAV 0 (95% confidence interval [CI] 1.7-5.3, p < 0.001). Of those with ISHLT CAV 1, 12% had ISHLT CAV 1b, which was associated with a 2.8 times greater risk of death/retransplantation compared to CAV 1a (95% CI 1.4-5.9, p = 0.003). In a subgroup of 158 patients with contemporary cardiac PET/CT, among those with CAV 1a, a myocardial blood flow reserve (MBFR) ≤2 was associated with a 4.6-fold risk of death/retransplantation compared to a normal MBFR (95% CI 1.7-12.6, p = 0.001).

Conclusion: Patients with CAV 1b had worse outcomes than those with CAV 1a. Among those with CAV 1a, the poorer outcomes than ISHLT CAV 0 observed were predominantly associated with reduced MBFR. These data suggest additional anatomic classification and physiologic assessment can further risk stratify those with ISHLT CAV 1.

Pulmonary hypertension puts strain on the right ventricle (RV), leading to the widespread practice of oversizing donor hearts to mitigate complications. However, contemporary evidence for this practice is neutral. We studied the relationship between donor-recipient predicted heart mass (D/R PHM) ratios and increases in donor left ventricle (LV) and RV mass. We also studied the relationship between predicted D/R PHM ratios and predicted D/R LV mass difference and RV mass difference. We find that increases in D/R PHM ratios result in minimal change in donor RV mass as well as minimal change in predicted D/R RV mass difference. However, increases in D/R PHM ratios were associated with marked increases in predicted D/R LV mass difference. We conclude that the utilization of donors with high predicted D/R PHM ratios generally does not result in the delivery of larger RVs to transplant recipients, but predominantly the delivery of larger LVs.

Heart transplant (HT) recipients experience high rates of cardiometabolic disease. Novel therapies targeting hyperlipidemia, diabetes, and obesity, including proprotein convertase subtilisin/kexin inhibitors, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 agonists, are increasingly used for cardiometabolic risk mitigation in the general population. However, limited data exist to support the use of these agents in patients who have undergone heart transplantation. Herein, we describe the mechanisms of action and emerging evidence supporting the use of novel pharmacologic agents in the post-HT setting for cardiometabolic risk mitigation and review evidence supporting their ability to modulate immune pathways associated with atherogenesis, epicardial adipose tissue, and coronary allograft vasculopathy.