Jayan Nagendran

Background.: Ex vivo lung perfusion (EVLP) has expanded the use of donor lungs by enabling ex vivo assessment, preservation, and rehabilitation before transplantation. Despite these advances, ischemia-reperfusion injury, inflammatory activation, pulmonary edema, and impaired lung mechanics continue to compromise graft quality and contribute to primary graft dysfunction. Inhaled and gaseous interventions have emerged as potential adjunctive therapies to improve donor lung preservation during EVLP; however, a standardized protocol has not yet been established. Methods.: PubMed and Embase were used to search human and animal studies evaluating inhaled and gaseous interventions administered during and after EVLP. Articles published from the database’s inception to September 22, 2025, were analyzed. Results.: Among the interventions examined, 10% carbon dioxide, carbon monoxide (CO), 40% oxygen (O ₂ ), hydrogen, 40 ppm nitric oxide (NO) with 60% O ₂ , 2% sevoflurane with 40%–50% O ₂ , 2-S-amino-6-boronohexanoic acid, fasudil, and β ₂ -adrenoreceptor agonists most effectively improved lung function. Interestingly, improvements from hydrogen and CO were observed after transplantation, rather than during EVLP, suggesting more persistent or delayed protective effects. Further optimized parameters were observed when moderate O ₂ concentrations (40%–60%) were combined with either CO, NO, or sevoflurane, compared with O ₂ alone. In contrast, argon, xenon, N-acetylcysteine, sevoflurane or NO with 6% O ₂ , and liquid ventilation demonstrated minimal benefit. Conclusions.: Inhaled interventions can attenuate both mechanical damage and inflammatory pathways, particularly when used in tailored combinations with 40%–60% O ₂ . Future research should prioritize standardizing protocols, optimizing gas composition and timing, and assessing long-term posttransplant outcomes to translate these findings into clinical practice.

Background: Coronary artery disease (CAD) and ischemic mitral regurgitation (IMR) commonly co-exist, yet the optimal intervention for these patients is unclear. Herein, we perform a systematic review and meta-analysis comparing the outcomes of patients with multivessel CAD and IMR undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Methods: PubMed and Embase were systematically searched for articles comparing outcomes of patients with CAD and IMR undergoing revascularization with CABG or PCI, with or without concomitant mitral valve interventions. Thousand two hundred eighty-five studies were identified and 8 were included in this review after full text review. The primary outcome of this study was mortality, and secondary outcomes included myocardial infarction, stroke, heart failure hospitalizations, and residual or recurrent mitral regurgitation. Results: Pooled analyses identified no significant differences in long-term mortality [odds ratio (OR): 1.13, 95% confidence interval (CI): 0.77–1.68, P = 0.53] with considerable heterogeneity between studies. However, following the exclusion of a single outlier, heterogeneity in the pooled analysis of long-term mortality improved and the outcome favored CABG over PCI (OR: 1.39, 95% CI: 1.06–1.83, P = 0.02). Rehospitalization for heart failure also favored CABG (OR: 1.49, 95% CI: 1.16–1.92, P = 0.002). Conclusion: This systematic review and meta-analysis suggested lower rates of long-term mortality and heart failure hospitalizations for CABG compared to PCI. CABG remains preferrable for patients with acceptable surgical risk, multivessel CAD, and IMR.

Background: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are the 2 revascularization modalities for patients with severe coronary artery disease. While CABG has often demonstrated benefits over PCI in multivessel coronary artery disease, analyses of cost effectiveness have previously shown conflicting results and are limited by sample size, follow‐up time, and lack of contemporary data. Methods: We performed an analysis of resource use following elective, urgent, or emergent PCI or CABG from January 1, 2009, to December 31, 2018, with up to 14 years of follow‐up. A provincial database was used to collect the associated data. The average cost for each event was calculated from Canadian Institute of Health Information data and was adjusted for inflation on the basis of the Bank of Canada consumer price index. Cost for each group was calculated for readmission to the hospital and repeat revascularization. Secondary outcomes included rates of death, myocardial infarction, rehospitalization, and repeat revascularization. Results: Of 23 243 patients who underwent angiography, 7359 were included in this study. Overall costs and costs per patient were significantly higher following PCI compared with CABG. Patients who underwent PCI required $19 165 per person in inflation‐adjusted health care resource costs compared with $12 612 for CABG. Furthermore, patients who underwent PCI had higher rates of death, myocardial infarction, rehospitalization, and repeat revascularization ( P <0.001). Conclusions: Patients with multivessel coronary artery disease experience fewer adverse events and use fewer health care resources after discharge following CABG compared with PCI. Appropriate selection of CABG versus PCI may help reduce readmissions and health care costs following revascularization.

Background.: Ex-situ heart perfusion (ESHP) enables improved donor heart preservation, yet still suffers functional decline. The perfusate is 1 area that requires optimization, especially with regard to hemoglobin (Hb) content. We sought to compare performance of concentrated, physiologic, and dilute perfusates in minimally damaged hearts. Methods.: Hearts of juvenile Yorkshire pigs (45–55 kg) were procured and subject to 11 h of working-mode ESHP in 1 of 4 groups varying in Hb: concentrated blood (CB, ~12 g/dL Hb, n = 4), whole blood (WB, ~8g/dL Hb, n = 6), plasma (~4g/dL Hb, n = 6, diluted with donor plasma), and control (~4g/dL Hb, n = 5, diluted with modified Krebs-Heinseleit). Functional, metabolic, and hemolytic markers were recorded and compared between groups statistically using appropriate statistical tests. Results.: CB hearts exhibited worsened decline from baseline in cardiac index, dP/dT max/min, and stroke work ( P < 0.05) and had greater elevations in hemolytic markers by end perfusion. Preservation of baseline cardiac index did not differ significantly between controls, WB, or plasma groups over time ( P > 0.05). The CB group displayed elevated early oxygen consumption compared with controls ( P < 0.05), with WB and plasma groups trending toward increased oxygen consumption. Lactate elevated over time in all groups, however, was not comparatively elevated within the CB group; it was reduced in the plasma group during early perfusion compared with control. Conclusions.: Hb dilution appears to lower absolute output but preserves baseline function. Supraphysiologic Hb elevation or sublethal blood cell damage exacerbates hemolysis, which contributes to functional decline during ESHP. Lactate evolution did not appear to associate with the degree of functional loss.

Systematic Review The impact of perfusate filtration or exchange on lung function during ex vivo lung perfusion (EVLP): a systematic review Maira Machhiwala, Ryaan El-Andari, Parham Hassanzadeh, Adrien Lam, Daniel Gutierrez, Max Buchko, Darren H. Freed, Jayan Nagendran

Background.: Lung transplant outcomes remain inferior to other solid organ transplants, but there is substantial heterogeneity. Some of this may relate to variations in clinical practice, but the degree to which this variability exists in Canada is not known. We sought to quantify the average practice and the variance among Canadian lung transplant physicians and surgeons via a national survey. Methods.: We conducted a digital survey of all physicians and surgeons in all Canadian lung transplant centers, including surgical centers (which perform transplants and provide care pre- and posttransplant) and nonsurgical centers (which provide care pre- and posttransplant). We reported overall averages and results stratified by center. Variability across centers was expressed as Pearson chi-square tests or ANOVA, whereas within-center variability was expressed as percentages and interquartile ranges. Results.: We identified 55 clinicians across Canada, of whom 44 (80%) completed the survey, including 31 physicians and 13 surgeons. Respondents were predominantly men (64%), of age 40–49 y (36%), and in practice for 5–15 y (47%). We found the most substantial variability between centers in infection prophylaxis (63%), immunosuppression/rejection management (59%), surgical and perioperative care, and candidate selection. Significant practice variability was also noted within centers. Conclusions.: This is the first portrait of average Canadian lung transplant practice and how these differ within and between centers. These differences may affect access to transplantation as well as posttransplant outcomes, and discussions about care standardization based on the best available evidence via existing national bodies would be worthwhile.

Background.: Von Willebrand factor (VWF) is a procoagulant glycoprotein expressed exclusively in endothelial cells and megakaryocytes. It mediates platelet adhesion to endothelial/subendothelial surfaces and initiates thrombogenesis. External stimuli, including hypoxia, were shown to upregulate VWF expression levels and alter its vascular tree expression pattern in the lung. Increased VWF levels are a significant risk factor for thrombus formation, a major complication in organ transplantation. Given that donor organs experience hypoxic conditions during transplantation, this study investigates whether hypoxia alters VWF expression and whether modifying organ preservation to reduce hypoxic exposure could prevent these alterations. Methods.: Porcine procured lungs were maintained in either static cold storage (SCS) or ex vivo lung perfusion with warm perfusion. Lung tissue biopsies were obtained immediately after organ procurement, 12 h post–cold storage, or post–warm perfusion. VWF RNA and protein expression levels and patterns were analyzed using reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence. Results.: Immunofluorescent analysis demonstrated that transplanted lungs maintained under SCS, but not ex vivo lung perfusion, exhibited VWF expression in an increasing number of microvascular endothelial cells, whereas warm perfusion led to a significant reduction in VWF mRNA levels, and it also showed a clear trend toward reduced protein expression compared with cold storage. Conclusions.: Increased VWF expression in microvascular endothelial cells under SCS may contribute to transplant-associated thrombogenicity. Decreasing VWF expression through ex vivo normothermic perfusion could significantly mitigate the risk of thrombogenic complications, a major complication of organ transplantation.

Background: Coronary artery bypass grafting(CABG) has long been the preferred treatment for left main coronary artery disease(LMCAD), although percutaneous coronary intervention(PCI) has been increasingly utilized. Despite numerous investigations seeking to identify the optimal revascularization strategy for LMCAD, limitations in sample size or follow-up duration have hindered definitive conclusions. Herein, we compare the long-term outcomes up to 14 years after CABG or PCI for patients with LMCAD. Methods: Data was retrospectively collected from a provincial database. The inclusion criteria is patients ≥18 years old, with LMCAD, and revascularization with CABG or PCI. The primary outcome is all-cause mortality. Secondary outcomes are any rehospitalization, myocardial infarction (MI), stroke, or repeat revascularization. Outcomes are adjusted for age, sex, and clinical comorbidities. The average age of the patients was 67 ± 9 years for the CABG patients and 71 ± 11 years for the PCI patients. 84.7% of the CABG patients and 71.5% of the PCI patients were male. Results: 5580 patients are identified with LMCAD between 2009 and 2018. 1706 patients (1180 CABG; 526 PCI) are included in the final analysis and followed until March 31, 2023. Rates of mortality at longest follow-up of 14 years are 40.0% for CABG and 58.4% for PCI (adjusted hazard ratio(aHR) 0.58, 95% confidence interval(CI) 0.48–0.70, p < 0.001). Rates of MI (10.7% vs 22.3%, aHR 0.40, 95% CI 0.29–0.55, p < 0.001) and repeat revascularization (5.4%vs16.3%, aHR 0.25, 95% CI 0.18–0.36, p < 0.001) favor CABG over PCI. Conclusions: Patients with LMCAD undergoing CABG experience significant benefit over PCI in terms of long-term mortality, MI, and required repeat revascularization. These finding suggest CABG should remain the preferred revascularization strategy for patients with LMCAD and acceptable surgical risk. Future studies should explore evolving PCI techniques and their impact on long-term outcomes.