Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial.

BACKGROUND: Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. METHODS: We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. FINDINGS: A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). INTERPRETATION: Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. FUNDING: XVIVO Perfusion.

Malignancies After Heart Transplantation.

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Cause-of-Death-Registry. A total of 664 patients were followed for a median of 7.7 years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7 years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx.

Malignancies After Lung Transplantation.

Lung transplantation (LTx) is a well-known treatment for end-stage lung disease. This study aimed to report the incidence of cancer after LTx and long-term outcome among lung transplant recipients with a pretransplant diagnosis of cancer. Patients who underwent LTx between 1990-2016 were included in the study. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer Registry and the Cause-of-Death registry. A total of 614 patients were followed for a median of 5.1 years. In all, 159 malignancies were diagnosed. The excess risk of cancer or standardized incidence ratio (SIR) following LTx was 5.6-fold compared to the general Swedish population. The most common malignancies were non-melanoma skin cancer (NMSC) (SIR 76.5 (95%CI 61.7-94.8); non-Hodgkin lymphoma (SIR 23.5, 95%CI 14.8-37.2); and lung cancer (SIR 8.89, 95%CI 5.67-13.9). There was no significant difference in overall survival between those with and without a history of cancer before LTx (p = 0.56). In total, 159 malignancies were identified after LTx, which was a 5.6-fold higher relative to the general population. A history of previous cancer yields similar survival in selected recipients, compared to those without cancer prior to LTx.

Sun protection behaviour in organ transplant recipients and non-transplant patients attending a dermatology outpatient clinic in Sweden: A questionnaire survey.

BACKGROUND/PURPOSE: Organ transplant recipients (OTRs) are at high risk of developing skin cancer and are therefore advised to protect their skin against ultraviolet radiation from the sun. Specialized OTR clinics with dermatological follow-up may improve sun habits among OTRs. In this study, we compared self-reported sun exposure and sun protection behaviour between OTRs and non-transplant patients (non-TPs) and between OTRs with and without special dermatological follow-up. METHODS: Patients from Sahlgrenska University Hospital, Gothenburg, Sweden, completed a sun exposure questionnaire. Between 2011 and 2015, 282 OTRs transplanted in the period 1976-2014 and 414 non-TPs were recruited among dermatological outpatients. Participants were stratified into five groups by their status as OTRs or non-TPs and by attendance to dermatological follow-up. RESULTS: More non-TPs than OTRs reported one or more sunburns in the past year, 46% vs. 20%, P < .0001). More OTRs with than OTRs without dermatological follow-up reported frequent use of sunscreens (63% vs 44%, P = .006). More OTRs with follow-up used one or more sun protection measure such as covering clothes, than other OTRs (54% vs 34%, P = .016). CONCLUSION: In this study, OTRs reported less sun exposure than non-TPs. Specialized dermatological follow-up seems to improve sun protection behaviour among OTRs. We suggest that specialized OTR clinics should be more broadly implemented.

Lung recruitment in the prone position after cardiac surgery: a randomised controlled study.

BACKGROUND: Atelectasis after cardiac surgery is common and promotes ventilation/perfusion mismatch, infection, and delayed discharge from critical care. Recruitment manoeuvres are often performed to reduce atelectasis. In severe respiratory failure, recruitment manoeuvres in the prone position may increase oxygenation, survival, or both. We compared the effects of recruitment manoeuvres in the prone vs supine position on lung aeration and oxygenation in cardiac surgical patients. METHODS: Subjects were randomised to recruitment manoeuvres (40 cm H2O peak inspiratory pressure and 20 cm H2O PEEP for 30 s) in either the prone or supine position after uncomplicated cardiac surgery. The co-primary endpoints were lung aeration (end-expiratory lung volume measured by electrical impedance tomography (arbitrary units [a.u.]) and lung oxygenation (ratio of arterial oxygen partial pressure to fractional inspired oxygen [Pao2/FiO2 ratio]). Secondary outcomes included postoperative oxygen requirement and adverse events. RESULTS: Thirty subjects (27% female; age, 48-81 yr) were recruited. Dorsal lung tidal volume was higher after prone recruitment manoeuvres (363 a.u.; 95% confidence intervals [CI], 283-443; n=15) after extubation, compared with supine recruitment manoeuvres (212 a.u.; 95% CI, 170-254; n=15; P<0.001). Prone recruitment manoeuvres increased dorsal end-expiratory lung volume by 724 a.u. (95% CI, 456-992) after extubation, compared with 163 a.u. decrease (95% CI, 73-252) after supine recruitment manoeuvres (P<0.001). The Pao2/FiO2 ratio after extubation was higher after prone recruitment manoeuvres (46.6; 95% CI, 40.7-53.0) compared with supine recruitment manoeuvres (39.3; 95% CI, 34.8-43.8; P=0.04). Oxygen therapy after extubation was shorter after prone (33 h [13]) vs supine recruitment manoeuvres (52 h [22]; P=0.01). No adverse events occurred. CONCLUSIONS: Recruitment manoeuvres in the prone position after cardiac surgery improve lung aeration and oxygenation. CLINICAL TRIAL REGISTRATION: NCT03009331.

Outcome and survival after open heart surgery for adults with congenital heart disease - a single center experience.

Introduction. Congenital heart disease (CHD) is the most common type of birth defect today. The adult congenital heart disease (ACHD) population is constantly growing and becoming older and more patients require cardiac surgery. The objective of this study was to review the surgical outcome of the open heart procedures performed on ACHD patients in the last 10 years at Sahlgrenska University Hospital (SUH) through a retrospective descriptive cohort study. Methods. A retrospective data collection was performed for 421 patients who underwent a total of 439 surgical procedures between 2009 and 2018 at the Cardiothoracic department in SUH. The primary outcomes were early (<30 days) and late survival. Secondary outcomes were postoperative complications and independent risk factors for postoperative complications. Results. 30-day mortality was 1.9%. Long-term survival after 3, 5 and 10 years were 96% ± 1, 94.3% ± 1.3 and 92.4% ± 1.8. 82 major complications occurred after 46 procedures (11.6%). The most common major complication was re-exploration due to hemorrhage. Risk factors for major complications were acute surgery and prolonged extracorporeal circulation time. 173 minor complications occurred after 90 procedures (22.5%). The most common minor complication was prolonged intensive care unit stay (>48 h). Conclusion. This study presents satisfactory early and midterm survival. The survival and frequency of major postoperative complications are well in line with what other studies have presented. Patients undergoing resternotomies had no increased risk for mortality or postoperative complications.

Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry.

AIMS: To evaluate the long-term use of secondary prevention medications [statins, ß-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality. METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for ß-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between ß-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54). CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of ß-blockers may be questioned.

Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation.

There is an ever increasing demand for donor lungs in patients waiting for transplantation. Lungs of many potential donors will be rejected if the standard criteria for donor assessment are followed. We have expanded our donor lung pool by accepting marginal donors and establishing a donation after circulatory death program. We have achieved comparable results using marginal donors and accepting donor lungs following donation after circulatory death. We present our assessment and technical guidelines on lung procurement taking into consideration an increasingly complex cohort of lung donors. These guidelines form the basis of the lung procurement training program involving surgical Fellows at the Alfred Hospital in Melbourne, Australia.

ECMO as a bridge to non-transplant cardiac surgery.

Cardiac surgery performed on patients in cardiogenic shock is associated with a high mortality and morbidity. This review outlines the current role of preoperative veno-arterial extra corporeal membrane oxygenation to allow hemodynamic stability and organ recovery before definitive cardiac surgery.

Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries.

INTRODUCTION: Ischaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart perfusion, known as non-ischaemic heart preservation (NIHP), theoretically limits the ischaemic time, while holding on to the known advantage of hypothermia and cardioplegia, a low metabolic rate. METHODS AND ANALYSIS: The NIHP 2019 study is an international, randomised, controlled, open, multicentre clinical trial in 15 heart transplantation centres in 8 European countries and includes 202 patients undergoing heart transplantation, allocated 1:1 to NIHP or ICSS. Enrolment is estimated to be 30 months after study initiation. The patients are followed for 12 months after transplantation.The primary objective is to evaluate the effect of NIHP on survival, allograft function and rejection episodes within the first 30 days after transplantation. The secondary objectives are to compare treatment groups with respect to survival, allograft function, cardiac biomarkers, rejection episodes, allograft vasculopathy, adverse events and adverse device effects within 12 months. ETHICS AND DISSEMINATION: This protocol was approved by the Ethics Committee (EC) for Research UZ/KU Leuven, Belgium, the coordinating EC in Germany (Bei Der LMU München), the coordinating EC in the UK (West Midlands-South Birmingham Research), the EC of Hospital Puerta de Hierro, Madrid, Spain, the EC of Göteborg, Sweden, the coordinating EC in France, the EC of Padova, Italy and the EC of the University of Vienna, Austria. This study will be conducted in accordance with current local regulations and international applicable regulatory requirements according to the principles of the Declaration of Helsinki and ISO14155:2020. Main primary and secondary outcomes will be published on modified intention-to-treat population and per-protocol population. TRIAL REGISTRATION NUMBER: NCT03991923.

Inspiratory and end-expiratory effects of lung recruitment in the prone position on dorsal lung aeration - new physiological insights in a secondary analysis of a randomised controlled study in post-cardiac surgery patients.

Background: Cardiac surgery produces dorso-basal atelectasis and ventilation/perfusion mismatch, associated with infection and prolonged intensive care. A postoperative lung volume recruitment manoeuvre to decrease the degree of atelectasis is routine. In patients with severe respiratory failure, prone positioning and recruitment manoeuvres may increase survival, oxygenation, or both. We compared the effects of lung recruitment in prone vs supine positions on dorsal inspiratory and end-expiratory lung aeration. Methods: In a prospective RCT, 30 post-cardiac surgery patients were randomly allocated to recruitment manoeuvres in the prone (n=15) or supine position (n=15). The primary endpoints were late dorsal inspiratory volume (arbitrary units [a.u.]) and left/right dorsal end-expiratory lung volume change (a.u.), prone vs supine after extubation, measured using electrical impedance tomography. Secondary outcomes included left/right dorsal inspiratory volumes (a.u.) and left/right dorsal end-expiratory lung volume change (a.u.) after prone recruitment and extubation. Results: The last part of dorsal end-inspiratory volume after extubation was higher after prone (49.1 a.u.; 95% confidence interval [CI], 37.4-60.6) vs supine recruitment (24.2 a.u.; 95% CI, 18.4-29.6; P=0.024). Improvement in left dorsal end-expiratory lung volume after extubation was higher after prone (382 a.u.; 95% CI, 261-502) vs supine recruitment (-71 a.u., 95% CI, -140 to -2; n=15; P<0.001). After prone recruitment, left vs right predominant end-expiratory dorsal lung volume change disappeared after extubation. However, both left and right end-expiratory volumes were higher in the prone group, after extubation. Conclusions: Recruitment in the prone position improves dorsal inspiratory and end-expiratory lung volumes after cardiac surgery. Clinical trial registration: NCT03009331.

A Retrospective Study of Posttransplant Amiodarone Exposition on Clad Development and Survival After Lung Transplantation.

BACKGROUND: Lung transplantation is a lifesaving procedure, still marred by worse results than other solid organ transplants. The 1-year mortality is 10%, and within 5 years after the procedure, half of patients develop chronic lung allograft dysfunction (CLAD), which also is the main limiting factor for long-term survival. Heart arrhythmias are also common directly after a lung transplant, and 1 treatment for this is the drug amiodarone. Recent research suggests that amiodarone exposure leads to activation of fibroblasts, a cell type that synthesizes stroma in the lung, associated with acute respiratory distress syndrome and CLAD. This study aims to retrospectively investigate the effect of posttransplant amiodarone treatment on survival and CLAD. MATERIAL AND METHODS: All patients transplanted at Sahlgrenska University Hospital between 2007 and 2018 were reviewed, and adult patients with a follow-up within Sweden were included. Of the 394 patients who met this inclusion criteria, retrospective data concerning postoperative complications and long-term outcomes were retrieved. A multivariable Cox proportional hazards model was applied to identify a set of independently significant predictors. RESULTS: Posttransplant use of amiodarone was associated with shorter survival (hazard ratio = 1.65; 95% confidence interval, 1.08-2.54; P = .02). Amiodarone exposure was not associated with CLAD (hazard ratio = 0.64; 95% confidence interval, 0.33-1.22; P = .17). CONCLUSIONS: An increased risk of death but not CLAD was observed in patients treated with amiodarone postoperatively after lung transplantation in the current cohort.

Outcomes and Long-term Survival After Pulmonary Retransplantation: A Single-Center Experience.

BACKGROUND: The median survival after lung retransplantation (ReLTx) reported to the International Society of Heart and Lung Transplantation is restricted to 2.5 years. We report the results after ReLTx from our center. METHODS: A retrospective data collection was performed for the 635 patients who underwent lung transplantation between 1991 and 2017 at our center. Recipient variables were compared between patients undergoing only primary lung transplantation (PLTx) and those undergoing PLTx and later ReLTx. Time to death was compared using the Kaplan-Meier method. The risk of ReLTx was analyzed in Cox regression models. Any interaction between type of transplantation, single/double, and PLTx/ReLTx was investigated. RESULTS: ReLTx was performed in 49 patients. Survival after ReLTx at 30 days and 1, 2, and 5 years was 90%, 76%, 71%, and 55%, respectively, and the corresponding survival after PLTx was 94%, 82%, 76%, and 61%, respectively. A hazard ratio of 1.73 for ReLTx was shown (95% confidence interval [CI], 1.14 to 2.63; P = .011). After adjustments for sex, age, diabetes, renal function, preoperative ventilator, and extracorporeal membrane oxygenation, the hazard ratio was 1.43 (95% CI, 0.90 to 2.26; P = .13). ReLTx was performed in 8 patients (16%) within the first year after PLTx. The 1-year survival for this group was 50% compared with 81% (P = .18) for patients who underwent ReLTx later than 1 year after the PLTx. One-year survival after double ReLTx was 60% (95% CI, 25% to 83%) compared with 79% (95% CI, 63% to 89%) for single ReLTx. CONCLUSIONS: ReLTx is a reasonable option for a selected group of patients. Ideally, a number of well-established risk factors are avoided and the ReLTx is performed more than 1 year after the PLTx.

Social Factors, Sex, and Mortality Risk After Coronary Artery Bypass Grafting: A Population-Based Cohort Study.

Background Little is known of the impact of social factors on mortality after coronary artery bypass grafting ( CABG ). We explored sex- and age-specific associations between mortality risk after CABG and marital status, income, and education. Methods and Results This population-based register study included 110 742 CABG patients (21.3% women) from the SWEDEHEART registry (Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies) operated 1992 to 2015. Cox regression models were used to study the relation between social factors and all-cause mortality. Never having been married compared with being married/cohabiting was associated with a higher risk in women than in men (hazard ratio 1.32, 95% CI 1.20-1.44) versus 1.17 (1.13-1.22), P=0.030 between sex. The lowest income quintile, compared with the highest, was associated with higher risk in men than in women (hazard ratio 1.44 [1.38-1.51] versus 1.25 [1.14-1.38], P=0.0036). Lowest education level was associated with higher risk without sex difference (hazard ratio 1.15 [1.11-1.19] versus 1.25 [1.16-1.35], P=0.75). For unmarried women aged 60 years at surgery with low income and low education, mortality 10 years after surgery was 18%, compared with 11% in married women with high income and higher education level. The median life expectancy was 4.8 years shorter. Corresponding figures for 60-year-old men were 21% versus 12% mortality risk at 10 years and 5.0 years shorter life expectancy. Conclusions There are strong associations between social factors and mortality risk after CABG in both men and women. These results emphasize the importance of developing and implementing secondary prevention strategies for CABG patients with disadvantages in social factors.

A single sequential snake saphenous vein graft versus separate left and right vein grafts in coronary artery bypass surgery: a population-based cohort study from the SWEDEHEART registry†.

OBJECTIVES: Our goal was to compare short- and midterm outcomes after coronary artery bypass grafting (CABG) using 2 different revascularization strategies. METHODS: A total of 6895 patients were included who had CABG in Sweden from 2009 to 2015 using the left internal mammary artery to the left anterior descending artery and either a single sequential saphenous vein graft connecting the left and right coronary territories to the aorta (snake graft, n = 2122) or separate vein grafts to both territories (n = 4773). Data were obtained from the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and the Swedish Patient Registry. The groups were compared using adjusted logistic regression for short-term (30-day) and Cox regression and flexible parametric survival models for midterm outcomes. Primary outcome was a composite of all-cause mortality, myocardial infarction (MI), reangiography and new revascularization. The median follow-up time was 35 months. RESULTS: At 30 days, the incidences of the composite end point [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.03-1.68; P = 0.03] and reangiography (OR 1.51, 95% CI 1.07-2.14; P = 0.02) were higher in the snake group. There was also a trend towards higher mortality (OR 1.47, 95% CI 0.97-2.22; P = 0.07). The event rates during the complete follow-up period were 6.5 (5.9-7.2) and 5.7 (5.3-6.1) per 100 person-years for the snake group and the separate vein group, respectively. At the midterm follow-up, no significant difference between the groups could be shown for the composite end point [hazard ratio (HR) 1.08, 95% CI 0.95-1.22; P = 0.24], mortality (HR 0.95, 95% CI 0.79-1.14; P = 0.56), MI (HR 1.11, 95% CI 0.88-1.41; P = 0.39) or new revascularization (HR 1.19, 95% CI 0.94-1.50; P = 0.15), whereas reangiography remained more common in the snake group (HR 1.25, 95% CI 1.05-1.48; P = 0.01). CONCLUSIONS: Snake grafts were associated with a higher rate of early postoperative complications, possibly reflecting a more demanding surgical technique, whereas midterm outcomes were comparable. Based on these data, one strategy cannot be recommended over the other.

Lung transplantation after ex vivo lung perfusion in two Scandinavian centres.

OBJECTIVES: We reviewed our combined clinical outcome in patients who underwent lung transplantation after ex vivo lung perfusion (EVLP) and compared it to the contemporary control group. METHODS: At 2 Scandinavian centres, lungs from brain-dead donors, not accepted for donation but with potential for improvement, were subjected to EVLP (n = 61) and were transplanted if predefined criteria were met. Transplantation outcome was compared with that of the contemporary control group consisting of patients (n = 271) who were transplanted with conventional donor lungs. RESULTS: Fifty-four recipients from the regular waiting list underwent transplantation with lungs subjected to EVLP (1 bilateral lobar, 7 single and 46 double). In the EVLP and control groups, arterial oxygen tension/inspired oxygen fraction ratio at arrival in the intensive care unit (ICU) was 30 ± 14 kPa compared to 36 ± 14 (P = 0.005); median time to extubation was 18 h (range 2-912) compared to 7 (range 0-2280) (P = 0.002); median ICU length of stay was 4 days (range 2-65) compared to 3 days (range 1-156) (P = 0.002); Percentage of expected forced expiratory volume at 1s (FEV1.0%) at 1 year was 75 ± 29 compared to 81 ± 26 (P = 0.18); and the 1-year survival rate was 87% [confidence interval (CI) 82-92%] compared to 83% (CI 81-85), respectively. Follow-up to a maximum of 5 years did not show any significant difference in survival between groups (log rank, P = 0.63). CONCLUSIONS: Patients transplanted with lungs after EVLP showed outcomes comparable to patients who received conventional organs at medium-term follow-up. Although early outcome immediately after transplantation showed worse lung function in the EVLP group, no differences were observed at a later stage, and we consider EVLP to be a safe method for increasing the number of transplantable organs.

Outcome after type A aortic dissection repair in patients with preoperative cardiac arrest.

AIM OF THE STUDY: Patients presenting with acute type A aortic dissection (ATAAD) and cardiac arrest before surgery are considered to have very poor prognosis, but limited data is available. We used a large database to evaluate the outcome of ATAAD patients with a cardiac arrest before surgery. METHODS: We evaluated 1154 surgically treated ATAAD patients from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database between 2005 and 2014. Patients with (n = 44, 3.8%) and without preoperative cardiac arrest were compared and variables univariably associated with mortality in the cardiac arrest group were identified. Median follow-up time was 2.7 years (interquartile range 0.5-5.5). RESULTS: Thirty-day mortality in the arrest and non-arrest group was 43.2% and 16.6%, respectively (odds ratio [OR] 3.83, CI 2.06-7.09; P < 0.001). In the nine patients with ongoing cardiopulmonary resuscitation when cardiopulmonary bypass was initiated, five died intraoperatively and one died after 65 days. In patients surviving the operation, stroke was significantly more common in the arrest group (48.4% vs 18.2%; OR 4.21, CI 2.05-8.67; P < 0.001). In total, 50.0% (22/44) of the arrest patients survived to the end of follow-up. Non-survivors in the arrest group more often had DeBakey type I dissection, cardiac tamponade, cardiac malperfusion and higher preoperative serum lactate (all P < 0.05). CONCLUSIONS: Early mortality and complications after ATAAD surgery in patients with a preoperative cardiac arrest are high, but mid-term outcome after surviving the initial period is acceptable. Preoperative cardiac arrest should not be considered an absolute contraindication for a surgical ATAAD repair.

Comparison of two strategies for ex vivo lung perfusion.

BACKGROUND: Two clinically used strategies for ex vivo lung perfusion (EVLP) were compared in a porcine model with respect to lung function, metabolism, inflammatory response, oxidative stress, and cell viability. METHODS: Porcine lungs (n = 20) were preserved, harvested, and kept cooled for 2 hours. After randomization, EVLP was performed using a cellular perfusate and open left atrium (COA group) or an acellular perfusate and a closed left atrium (ACA group). Oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen), compliance, dead space, weight, and perfusate oncotic pressure were registered before and after a 4-hour period of reconditioning. Lung tissue samples were collected before and after EVLP for quantitative polymerase chain reaction analysis of gene expression for inflammatory markers, measurement of tissue hypoxia (hypoxia inducible factor-1α) and oxidative stress (ascorbyl radical), and viability (trypan blue staining) and lung histopathology. RESULTS: In 3 of 10 lungs undergoing EVLP in the ACA group, EVLP was terminated prematurely because of severe lung edema and inability to perfuse the lungs. There were no significant differences in changes of lung oxygenation or pulmonary vascular resistance between groups. Compliance decreased and lung weights increased in both groups, but more in the ACA group (p = 0.083 and p = 0.065, respectively). There was no obvious difference in gene expression for hypoxia inducible factor-1α, inflammatory markers, free radicals, or lung injury between groups. CONCLUSIONS: Lung edema formation and decreased lung compliance occurs with both EVLP techniques but were more pronounced in the ACA group. Otherwise, there were no differences in lung function, inflammatory response, ischemia/reperfusion injury, or histopathologic changes between the EVLP techniques.

Transplantation after ex vivo lung perfusion: A midterm follow-up.

BACKGROUND: A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. METHODS: Single-center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period. Short-term follow-up included time to extubation, time in the intensive care unit, and the presence of primary graft dysfunction at 72 hours postoperatively. Mortality and incidence of chronic lung allograft dysfunction were monitored for up to 4 years after discharge. RESULTS: During a 4-year period, 32 pairs of initially rejected donor lungs underwent EVLP. After EVLP, 22 double lungs and 5 single lungs were subsequently transplanted. During this period, 145 patients received transplants of conventional donor lungs that did not have EVLP and constituted the control group. Median time to extubation was 7 hours in the EVLP group and 6 hours in the non-EVLP control group (p = 0.45). Median intensive care unit stay was 4 days vs. 3 days, respectively (p = 0.15). Primary graft dysfunction grade > 1 was present in 14% in the EVLP group and in 12% in the non-EVLP group at 72 hours after transplant. Survival at 1 year was 92% in the EVLP group and 79% in the non-EVLP group. Cumulative survival and freedom from retransplantation or chronic rejection were also comparable between the 2 groups (p = 0.43) when monitored up to 4 years. CONCLUSIONS: Selected donor lungs rejected for transplantation can be used after EVLP. This technique is effective for selection of transplantable donor lungs. Patients who received lungs evaluated under EVLP have short-term and midterm outcomes comparable to recipients of non-EVLP donor lungs.

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

OBJECTIVES: Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. METHODS: In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. RESULTS: After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. CONCLUSIONS: In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity.