Journal of Heart and Lung Transplantation最新文献

Background: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.

Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1^-/-) mice.

Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1^-/- donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1^-/- donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1^-/- recipient.

Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.

Background: Infections after orthotopic heart transplantation (OHT) cause significant morbidity and mortality. Concurrent with increased pre-OHT temporary mechanical circulatory support (MCS), there have been recent concerns of a perceived increase in infections post-OHT. We examined the association between pre-OHT temporary versus durable MCS and post-OHT infection.

Methods: We performed a single-center retrospective review of patients who received OHT at Tufts Medical Center between January 2014 and April 2022. Our composite outcome was the occurrence of bacteremia, invasive fungal infections, opportunistic infections, or skin/soft tissue infections of device sites within 1-year post-OHT. We used Cox proportional hazards models to assess the relationship between the type of pre-OHT MCS and time to the first infection, treating death from other causes as a competing risk. We addressed confounding with 2 statistical methods: propensity score (PS) with inverse probability weighting (IPW) and an instrumental variable (IV) analysis.

Results: Of the 320 OHT recipients, 268 required MCS before OHT; 192 were managed with durable MCS and 76 with temporary MCS. Patients receiving pre-OHT temporary MCS had no difference in time to first infection (unadjusted hazard ratio [HR] 0.77, 95% CI 0.41-1.44) compared to durable MCS. Results were similar in the model employing PS with IPW (HR 0.61, 95% CI 0.29-1.27) and the IV analysis (HR 0.28, 95% CI 0.26-2.36).

Conclusions: Pre-OHT temporary MCS was not associated with the composite outcome of bacteremia, invasive fungal infections, opportunistic infections, or skin/device site infections post-OHT compared to durable MCS in this single-center cohort.

Background: Stroke remains a devastating complication of durable left ventricular assist device (LVAD) therapy. This study evaluated the incidence and risk factors for early stroke within 7 days following LVAD implantation investigating both traditional pre-implant and new intraoperative variables collected by The Society of Thoracic Surgeons (STS) Intermacs National Database.

Methods: STS Intermacs was queried for patients undergoing implantation of a fully magnetically levitated centrifugal LVAD between November 25, 2020 and June 30, 2023. STS Intermacs stroke definitions were used to identify patients who suffered a stroke within the first 7 postoperative days (POD). A multivariable logistic regression model was created to generate adjusted odd ratios (OR) for variables associated with early stroke.

Results: Among 6,950 patients in the study cohort, 5.9% (413/6950) developed a stroke after a median follow-up of 11 months, with 50% (205/413) of strokes occurring within 7 days after LVAD implantation. Of the strokes occurring during POD 0-7, 70% (144/205) occurred on POD 0-2. By multivariable analysis, the following factors were associated with early stroke: older age (70 vs 50; OR 1.4, p = 0.0129), white race (OR 1.5, p = 0.0078), pre-implant temporary mechanical circulatory support (MCS) bridge (temporary LVAD only: OR 1.6, extracorporeal membrane oxygenation [ECMO] only: OR 1.7, combination of both devices: OR 3.3; p = 0.0001) and presence of an unremoved left atrial clot (OR 8.0, p < 0.0001).

Conclusions: A significant proportion of strokes occur within the first 7 days following LVAD implantation, particularly within the first 2 days. In addition to pre-implant variables, we identified modifiable intraoperative factors associated with stroke that provide an opportunity for further risk mitigation and improvement in quality of care.

Background: Partial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart.

Methods: Cardiac transplant recipients (n = 232) were recruited from outpatient clinic at a single transplant center in the United Kingdom. Participants were each tested once for the presence of sympathetic reinnervation of the sinus node using the low-frequency component of power spectral analysis of heart rate variability, with a cutoff defined as 2 standard deviations above the mean for denervated participants (those tested <56 days posttransplant). Time course was calculated based on the timing of testing posttransplant. Patients were then followed up over a period of up to 27 years after transplant for survival analysis.

Results: The overall prevalence of cardiac sympathetic reinnervation in the 225 patients tested >56 days posttransplant was 64.9%. Sympathetic reinnervation primarily occurred in the first 18 months after transplant, with a plateau thereafter. The prevalence in participants tested >18 months posttransplant was 69.6%. In Kaplan-Meier survival analysis, sympathetic reinnervation was associated with significantly improved survival (Log-rank p = 0.019), with a median survival time for reinnervated patients of 19.9 years compared with 14.4 years for the denervated group.

Conclusions: Sympathetic reinnervation of the sinus node occurs mostly within 18 months of transplant, is found in 70% of cardiac transplant recipients tested >18 months posttransplant, and is associated with significantly improved long-term survival.

Temporary mechanical circulatory support (tMCS) using extracorporeal life support (ECLS), has been widely implemented in patients with cardiogenic shock (CS), although evidence regarding its efficacy and safety remains unclear. This lack of clarity has recently raised concerns about the role of tMCS in CS management. Conducting randomized controlled trials (RCTs) in the context of CS poses significant challenges due to ethical considerations and logistical complexities. In response to these challenges, emulated trials (ETs) are emerging as a promising alternative. By incorporating design features from idealized RCTs, they use robust and rigorous methods to assess the efficacy and safety of health interventions in real-life settings, using observational data. In our manuscript, we highlight the complementary nature of RCT and ETs by evaluating tMCS for CS patients. While RCTs follow a rigorous experimental design and provide reliable evidence, ETs can swiftly estimate the risk-benefit ratio without encountering logistical barriers thereby offering clinicians' early reassurance about the potential benefits of routinely used interventions. Furthermore, ETs offer potential value in unethical situations (refractory cardiac arrest or "crash and burn" CS) where interventional therapies, such as tMCS, are used as a last resort.

Right ventricular outflow tract (RVOT) function is not systematically quantified by three-dimensional (3D) echocardiography. We tested the hypothesis that loss of RVOT function in pulmonary hypertension (PH) is related to disease severity independently of other echocardiographic parameters. In this observational study, patients with PH, disease controls, and a matched healthy control group underwent 3D echocardiography and RVOT analysis using ReVISION software. The study included 43 patients (38 with PH, 5 disease controls) and 43 healthy controls. Median 3D RVOT-ejection fraction (EF) was 30.4% in the patients and 44.2% in the healthy controls (p < 0.001). Patients with low 3D RVOT-EF (<30.4%) were more frequently categorized in higher-risk groups and had a higher incidence of clinical worsening than those with high 3D RVOT-EF. Even in patients with RV-EF ≥35%, those with low 3D RVOT-EF had worse outcomes. Segmental RVOT analysis identifies high-risk patients even with normal overall RV function.

Mucosal or endobronchial biopsies (EBB) are typically used in the diagnosis of directly visualized bronchial lesions, infection, and sarcoidosis, but their utility in the evaluation of lung transplant recipients is controversial. EBB represents an attractive alternative to transbronchial biopsy (TBB): EBB provides straightforward sampling of airway pathology with decreased complication rates due to minimal and visualizable bleeding and the elimination of pneumothorax risk. In lung transplant recipients, EBB may be obtained when TBB is too high-risk, including in the setting of acute lung allograft dysfunction (ALAD) requiring mechanical ventilation or in advanced chronic lung allograft dysfunction (CLAD). Most centers do not include EBB in post-transplant surveillance or for-cause bronchoscopy protocols, possibly due to a lack of a common histologic interpretation system. Previous work has demonstrated that lymphocytic inflammation in lung transplant EBB is associated with acute cellular rejection and future risk for CLAD, but these have not translated into subsequent studies on clinical utility or into clinical practice. Recent multicenter studies suggest that gene expression-based diagnostics leveraging EBB may outperform histologic grading and provide important prognostic utility in predicting graft loss. Herein, we will review what is known about the lung transplant mucosa including recent diagnostic advances and propose how EBB analyses could be incorporated into research studies and clinical workflows. We propose that mucosal sampling could provide safe, consistent, and informative data to improve patient outcomes after lung transplant.