Faculty Bibliography

BACKGROUND:The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. METHODS:Retrospective study of 401 consecutive patients undergoing PEA at our institution between 08/2005 and 03/2020 was performed. Primary outcome was need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. RESULTS:Females (n=203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final TPR after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p<0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p=0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs. 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04). CONCLUSIONS:Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients is important. Further investigations into possible mechanisms to explain the differences is warranted.

BACKGROUND:The effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample. METHODS:Data on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation. RESULTS:Among 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score-matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P = .031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P < .01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation. CONCLUSIONS:PIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers.

BACKGROUND:Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality. METHODS:Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons' reports and assessors' evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes. RESULTS:Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable. CONCLUSION:This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.

Lung transplantation remains the only available therapy for many patients with end-stage lung disease. The number of lung transplants performed has increased significantly, but development of the field was slow compared with other solid-organ transplants. This delayed growth was secondary to the increased complexity of transplanting lungs; the continuous needs for surgical, anesthetics, and critical care improvements; changes in immunosuppression and infection prophylaxis; and donor management and patient selection. The future of lung transplant remains promising: expansion of donor after cardiac death donors, improved outcomes, new immunosuppressants targeted to cellular and antibody-mediated rejection, and use of xenotransplantation or artificial lungs.

Xenotransplantation promises to alleviate the issue of donor organ shortages and to decrease waiting times for transplantation. Recent advances in genetic engineering have allowed for the creation of pigs with up to 16 genetic modifications. Several combinations of genetic modifications have been associated with extended graft survival and life-supporting function in experimental heart and kidney xenotransplants. Lung xenotransplantation carries specific challenges related to the large surface area of the lung vascular bed, its innate immune system's intrinsic hyperreactivity to perceived 'danger', and its anatomic vulnerability to airway flooding after even localized loss of alveolocapillary barrier function. This article discusses the current status of lung xenotransplantation, and challenges related to immunology, physiology, anatomy, and infection. Tissue engineering as a feasible alternative to develop a viable lung replacement solution is discussed.

BACKGROUND:Evolution of surgical practice is influenced by publications in the leading journals of that field. If the authorship of a publication lacks geographical diversity, this could create bias and limit generalizability of the evidence. Accordingly, we conducted a geographical analysis of the leading Cardiothoracic Surgery journals worldwide. METHODS:Using 2020 Impact Factor, we searched the leading Cardiothoracic Surgery journals over the past decade. Only original articles were included. Data regarding first, second and last authors were extracted from every article. From this, we analysed country of affiliation, highest academic degree obtained and author location by metropolitan or rural setting. RESULTS:A total of 12,706 original articles were published in the top 5 ranked Cardiothoracic journals between 2011 and 2020. Authors originated from 69 countries, with the majority being from North America and Western Europe. The United States was the most common country of affiliation (42.8%) in all five journals, with New York City the most prominent city. A total of  63.7% of the authorship originated from large metropolitan areas (estimated as population greater than 500,000 residents), and the most common degrees obtained by authors were MD and PhD. CONCLUSION/CONCLUSIONS:The prominent Cardiothoracic authorship is predominantly located in Western countries, most commonly large metropolitan centers in the United States. This raises questions as to whether the literature adequately reflects populations in other geographical areas such as the continents of South America and Africa and rural settings. Leading journals should consider policies which encourage publication by authors from geographical locations that are underrepresented globally.

Objectives/UNASSIGNED:Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, though little data exists evaluating the safety and feasibility of proning ARDS patients on extracorporeal membrane oxygenation (ECMO). Methods/UNASSIGNED:, 2020 was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results/UNASSIGNED:of 86 pre to 103 post (p<0.0001). Mean ECMO flow was unchanged. Conclusions/UNASSIGNED:Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

OBJECTIVE:Determine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension. METHODS:Retrospective analysis of a prospective cohort of 401 consecutive Canadian patients undergoing PEA between August 2005 and March 2020 in Toronto. The outcome of segmental disease defined as Jamieson type 3 was compared with more proximal disease defined as Jamieson type 1 and 2. The cohort was divided into 3 intervals to analyze the trend over time: 2005-2010, 2011-2015, and 2016-2020. RESULTS:in type 1 or 2 disease (P = .07). Mortality after PEA was similar between type 3 and type 1 and 2 disease at 30-days (2.8% vs 2.3%; P = .8) and at 1 year (7.7% vs 5.5%; P = .4). At 5 years, the survival was lower in type 3 disease (80% vs 91% in type 1 or 2 disease; P = .002). Type 3 disease was an independent predictor for the initiation of pulmonary hypertension-targeted medical therapy after PEA with a cumulative incidence of 38% at 10 years compared with 20% in type 1 and 2 disease (P < .0001). Post-PEA balloon pulmonary angioplasty was predominantly performed in type 3 disease (8% vs 1% in more type 1 or 2 disease; P = .0002). CONCLUSIONS:PEA achieved excellent early and long-term results in segmental chronic thromboembolic pulmonary hypertension. However, patients with segmental disease are at increased risk of requiring additional therapy after PEA and should be carefully monitored.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.