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Lung transplantation remains the best option for patients with end-stage lung disease. However, this operation has historically carried significant potential morbidity. To improve near-term patient outcomes, attempts have been made to decrease invasiveness, but this is limited by the complex nature of the operation and the anatomy of the chest. To facilitate further reduction in incision size and augment our existing minimally invasive approach, we developed a novel technique utilizing the Da Vinci robotic system to implant a right lung in a 69-year-old recipient. [ABSTRACT FROM AUTHOR]

We describe a patient with a HeartMate 3 left ventricular assist device in whom we attempted transcatheter aortic valve implantation for severe aortic regurgitation. The valve migrated into the left ventricle and lodged on the left ventricular assist device inflow cannula. Caution should be exercised when considering the use of transcatheter aortic valve implantation in patients with an implanted left ventricular assist device, with pure aortic regurgitation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure and mitochondria play an important role in this mode of cell death. In this study, activity of the Bcl-2 family of mitochondrial apoptotic proteins and their regulator (p53) were assessed during the transition to heart failure. Methods: Ten adult male sheep were banded with a variable aortic constriction device. This was progressively inflated to increase left ventricular (LV) afterload. The sheep were monitored echocardiographically, measuring LV Mass Index (LVMI), diastolic LV Internal Diameter (LVIDd) and Fractional Shortening (FS). Serial LV endomyocardial biopsies were obtained, to measure expression of p53 and Bcl-2 family proteins by Western blotting. Results: Over the first 3–4 weeks, the sheep developed hypertrophy (LVMI 79.5±4.6 vs. 44.0±3.0 g/m2, p <0.01), followed by gradual LV dilatation (LVIDd 4.23±0.08 vs. 3.39±0.07 cm, p <0.01). Ventricular function remained stable until 7–8 weeks post banding, when there was significant deterioration (FS 18.3±2.4 vs. 46.9±2.6%, p <0.01), associated with clinical heart failure. Upregulation of the Bax/Bcl-2 ratio, associated with increased levels of p53, was demonstrated in each of the echocardiographically defined stages (LV hypertrophy, LV dilatation and LV failure). In parallel, significantly higher levels of anti-apoptotic protein (Bcl-xL) was associated with LV dilatation and failure. Conclusions: Upregulation of Bax/Bcl-2 ratio occurs during the transition to heart failure and in particular with the initial hypertrophic response. Increase in expression of the anti-apoptotic protein Bcl-xL suggests possible concomitant compensatory mechanisms being activated during the transition to heart failure. [Copyright &y& Elsevier]

Objectives: Pressure overload plays an important role in left ventricular remodelling and the development of heart failure. The underlying molecular mechanisms behind these processes are poorly understood at the myocyte level. To investigate this, we developed an ovine model of pressure overload-induced heart failure, in which serial left ventricular biopsies were obtained. Methods: Adult male sheep were chronically banded with a novel variable aortic constriction device. This was progressively inflated via a subcutaneous port to increase left ventricular afterload. The animals were monitored clinically and echocardiographically. Serial left ventricular endomyocardial biopsies were obtained via the right external carotid artery under fluoroscopic guidance. They were used to measure mRNA expression of the genetic regulators of apoptosis by reverse transcription polymerase chain reaction. In a subset of the animals, once left ventricular failure had been established, the constriction device was deflated to produce unloading of the left ventricle. Results: Ten of the 17 sheep banded developed left ventricular failure. Over the first 3–4 weeks, left ventricular mass index increased acutely (88±18 vs. 44±10 g/m2, P<0.01) followed by gradual left ventricular dilatation (diastolic left ventricular internal diameter 4.1±0.7 vs. 3.2±0.3 cm, P<0.01). Ventricular function remained stable until 7–8 weeks postoperatively, when there was significant deterioration (fractional shortening 17±8 vs. 40±8%, P<0.01) associated with clinical heart failure. Expression of the pro-apoptotic genes (bax and Fas) increased significantly following inflation of the constriction device and persisted through the transition to left ventricular failure. Following deflation of the constriction device, myocardial contractility gradually improved over a 3 week period (fractional shortening 32±1 vs. 17±8%). Conclusions: Progressively increasing the afterload on the left ventricle produces a clinical and echocardiographical picture of chronic heart failure. Obtaining myocardial tissue during this transition will allow the molecular correlates of pressure overload-induced heart failure and potential myocardial recovery to be investigated. [Copyright &y& Elsevier]

Minimally invasive (MI) approaches to lung transplantation (LTx) offer the prospect of faster recovery compared to traditional incisions, however, little data exist describing the impact of surgical technique on early outcomes and analgesia use. A prospectively maintained institutional registry identified 170 patients who underwent LTx between January, 2017 and June, 2022. Post-COVID acute respiratory distress syndrome, repeat, and multiorgan transplants were excluded (n = 27) leaving 37 MILTx and 106 traditional LTx patients. Propensity score matching by age, sex, body mass index, diagnosis, lung allocation score, double vs. single lung, hypertension, diabetes, and hospitalization status created 37 pairs. Before matching, MILTx patients were more often male (70% vs 43%) and more likely to receive grafts from younger (31 vs 42 years), circulatory death donors (19% vs 6%) compared with traditional LTx patients (all p < 0.05). After matching, there were no differences in graft warm ischemia or operative duration (both p > 0.05). Postoperatively, MILTx experienced shorter intensive care unit (ICU) (4.3 [IQR 3.1–5.5] vs 8.2 [IQR 3.7–10.8] days) and hospital lengths of stay (LOS) (13 [IQR 11–15] vs 17 [IQR 12–25] days) (both p < 0.05). Among patients surviving to discharge, MILTx patients required fewer opioid prescriptions at discharge (38% vs 66%, p = 0.008) and had improved pulmonary function at 3 months (Forced expiratory volume in 1 second 82 [IQR 72–102] vs 77 [IQR 52–88]% predicted; forced vital capacity 78 [IQR 65–92] vs 70 [IQR 62–80]% predicted] (both p < 0.05). Minimally invasive LTx techniques demonstrate potential advantages over traditional approaches, including reduced ICU and hospital LOS, lower opioid use on discharge, and improved early pulmonary function. [ABSTRACT FROM AUTHOR]

Background: Survival, functional outcomes, and quality of life after left ventricular assist device (LVAD) are ill-defined in elderly patients, and with new-generation devices.Objectives: This study sought to evaluate survival, functional outcomes, and quality of life after LVAD in contemporary practice.Methods: Adults receiving durable LVADs between January 1, 2010, and March 1, 2020, were identified from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database. The primary outcome was adjusted survival; secondary outcomes included quality of life rated using a visual analogue scale (where 0 represents "worst health" and 100 "best health"); 6-minute walk distance; stroke; device malfunction; and rehospitalization, stratified by patient age. Median follow-up was 15 months (IQR: 6-32 months).Results: The cohort comprised 68.9% (n = 16,808) patients aged <65 years, 26.3% (n = 6,418) patients aged 65-75 years, and 4.8% (n = 1,182) patients aged >75 years, who were predominantly male (n = 19,119, 78%) and on destination therapy (n = 12,425, 51%). Competing outcomes analysis demonstrated mortality (70% CIs) of 34% (33%-34%), 54% (54%-55%), and 66% (64%-68%) for patients aged <65, 65-75, and >75 years, respectively, which improved during the study in patients aged >75 years. Newer-generation devices were associated with reduced late mortality (HR: 0.35; 95% CI: 0.25-0.49). Stroke, device malfunction or thrombosis, and rehospitalizations decreased with increasing age (all P < 0.01). Median 6-minute walk distance increased from 0 feet (IQR: 0-665 feet) to 1,065 feet (IQR: 642-1,313 feet) (P < 0.001), and quality of life improved from 40 (IQR: 15-60) to 75 (IQR: 60-90) (P < 0.001) after LVAD in all age groups.Conclusions: In elderly patients, LVADs are associated with increased functional capacity, similar improvements in quality of life, and fewer complications compared with younger patients. [ABSTRACT FROM AUTHOR]

Studies examining heart transplantation disparities have focused on individual factors such as race or insurance status. We characterized the impact of a composite community socioeconomic disadvantage index on heart transplantation outcomes. From the Scientific Registry of Transplant Recipients (SRTR), we identified 49,340 primary, isolated adult heart transplant candidates and 32,494 recipients (2005-2020). Zip code-level socioeconomic disadvantage was characterized using the Distressed Community Index (DCI: 0—most prosperous, 100—most distressed) based on education, poverty, unemployment, housing vacancies, median income, and business growth. Patients from distressed communities (DCI ≥ 80) were compared to all others. Patients from distressed communities were more often non-white, less educated, and had public insurance (all p < 0.01). Distressed patients were more likely to require ventricular assist devices at listing (29.4 vs 27.1%) and before transplant (44.8 vs 42.0%, both p < 0.001), and they underwent transplants at lower-volume centers (23 vs 26 cases/year, p < 0.01). Distressed patients had higher 1-year waitlist mortality or deterioration (12.3% [95% confidence interval (CI) 11.6-13.0] vs 10.9% [95% CI 10.5-11.3]) and inferior 5-year survival (75.3% [95% CI 74.0-76.5] vs 79.5% [95% CI 79.0-80.0]) (both p < 0.001). After adjustment, living in a distressed community was independently associated with an increased risk of waitlist mortality or deterioration hazard ratio (HR 1.10, 95% CI 1.02-1.18) and post-transplant mortality (HR 1.13, 95% CI 1.06-1.20). Patients from socioeconomically distressed communities have worse waitlist and post-transplant mortality. These findings should not be used to limit access to heart transplantation, but rather highlight the need for further studies to elucidate mechanisms underlying the impact of community-level socioeconomic disparity. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated racial and gender disparities in lung allocation, but contemporary data regarding socioeconomic disparities in post-transplant outcomes are lacking. We evaluated the impact of a composite socioeconomic disadvantage index on post-transplant outcomes. The Scientific Registry of Transplant Recipients identified 27,763 adult patients undergoing isolated primary lung transplantation between 2005 and 2020. Zip code-level socioeconomic distress was characterized using the Distressed Communities Index (DCI: 0-no distress, 100-severe distress) based on education level, poverty, unemployment, housing vacancies, median income, and business growth, and patients were stratified into high (DCI ≥60) or low (DCI <60) distressed groups. Recipients from high-distress communities (n = 8006, 28.8%) were younger (59 years [interquartile range {IQR} 50-64] vs 61 years [IQR 52-66]), less often white (73 vs 85%), less likely to have a college degree (45 vs 59%), and more likely to have public insurance (57 vs 49%, all p < 0.001) compared to those from low-distress communities. Additionally, high-distress recipients were more likely to have group A diagnoses (32 vs 27%) and undergo bilateral lung transplants (72.4 vs 69.3%, all p < 0.001). Post-transplant survival at 5 years was 55.7% (95% confidence interval [CI]: 54.4-56.9) in high-distress recipients and 58.2% (95% CI: 57.4-58.9) in low-distress recipients (p = 0.003). After adjustment, high distress level was independently associated with an increased risk of 5-year mortality (hazard ratio:1.09, 95% CI:1.04-1.15). Recipients from distressed communities are at increased mortality risk following lung transplantation. Efforts should be focused on increased resource allocation and further study to better understand factors which may mitigate this disparity. [ABSTRACT FROM AUTHOR]

Some degree of ischemia is inevitable in organ transplantation, and for most, if not all organs, there is a relationship between ischemic time and transplant outcome. The contribution of ischemic time to lung injury is unclear, with conflicting recent data. In this study, we investigate the impact of ischemia time on survival after lung transplantation in a large national cohort. We studied the outcomes for 1,565 UK adult lung transplants over a 12-year period, for whom donor, transplant, and recipient data were available from the UK Transplant Registry. We examined the effect of ischemia time (defined as donor cross-clamp to recipient reperfusion) and whether standard cardiopulmonary bypass was used using Cox proportional hazards models, adjusting for other risk factors. The total ischemic time increased from a median under 5 hours in 2003 to over 6.2 hours in 2013. Our findings show that, when the cardiopulmonary bypass was used, there was an increase in the hazard of death (of 13% [95% CI: 5%-21%] for 1-year patient survival) for each hour of total ischemic time. However, if the cardiopulmonary bypass was not used for implantation, this link disappeared—there was no statistically significant change in mortality with increasing ischemic time. We document that avoidance of bypass may remove ischemic time, within the limits of our observed range of ischemic times, as a risk factor for poor outcomes. Our data add to the evidence that bypass may be harmful to the donor lung. [ABSTRACT FROM AUTHOR]

The authors comment on the article "Does Controlled Donation After Circulatory Death Violate the Dead Donor Rule (DDR)?," by Nielsen Busch et al., focusing on the challenges related to concerns about the DDR contradicts controlled donation after circulatory death (cDCD) protocols and the loss of recoverable organs. They focus on acknowledging clinicians' concern about death and cDCD protocols and administrative, psychosocial or ethical issues that pose challenges for organ procurement experts.

Thoracoabdominal normothermic regional perfusion has emerged as an alternative method to procure donation after circulatory death (DCD) hearts, but its impact on concomitantly procured lung allografts remains unclear. The United Network for Organ Sharing database identified 627 DCD donors whose hearts were procured (211 in situ perfused, 416 directly procured) between December 2019 to December 2022. Lung utilization rates were 14.9% (63/422) for in situ perfused donors and 13.8% (115/832) for directly procured donors (p = 0.80). Following transplantation, lung recipients from in situ perfused donors required numerically lower rates of extracorporeal membrane oxygenation (7.7% vs 17.0%, p = 0.26) and mechanical ventilation (34.6% vs 47.2%, p = 0.29) at 72 hours. Six-month post-transplant survival was similar between groups (85.7% vs 89.1%, p = 0.67). These results suggest that the use of thoracoabdominal normothermic regional perfusion in DCD heart procurement may not adversely impact recipients of concomitantly procured lung allografts. [ABSTRACT FROM AUTHOR]

Given ongoing donor shortages, appropriate patient selection for dual-organ transplantation is critical. We evaluated outcomes of heart retransplant with simultaneous kidney transplant (HRT-KT) vs isolated heart retransplant (HRT) across varying levels of renal dysfunction. The United Network for Organ Sharing database identified 1189 adult patients undergoing heart retransplantation between 2005 and 2020. Recipients undergoing HRT-KT (n = 251) were compared to those undergoing HRT (n = 938). The primary outcome was 5-year survival; subgroup analyses and multivariable adjustment were performed utilizing the following 3 estimated glomerular filtration (eGFR) groups: <30 ml/min/1.73m2, 30-45 ml/min/1.73m2, and >45 ml/min/1.73m2. HRT-KT recipients were older and had longer waitlist times, longer inter-transplant periods, and lower eGFR levels. HRT-KT recipients were less likely to require pretransplant ventilator (1.2% vs 9.0%, p < 0.001) or ECMO (2.0% vs 8.3%, p < 0.001) support but were more likely to have severe functional limitation (63.4% vs 52.6%, p = 0.001). After retransplantation, HRT-KT recipients had less treated acute rejection (5.2% vs 9.3%, p = 0.02) and more dialysis requirement (29.1% vs 20.2%, p < 0.001) before discharge. Survival at 5-years was 69.1% after HRT and 80.5% after HRT-KT (p < 0.001). After adjustment, HRT-KT was associated with improved 5-year survival among recipients with eGFR <30 ml/min/1.73m2 (HR:0.42, 95% CI: 0.26-0.67) and 30 to 45 ml/min/1.73m2 (HR:0.29, 95% CI 0.13-0.65), but not among those with eGFR>45 ml/min/1.73sm2 (HR 0.68, 95% CI 0.30-1.54). Simultaneous kidney transplantation is associated with improved survival following heart retransplantation in patients with eGFR <45 ml/min/1.73m2 and should be strongly considered to optimize organ allocation stewardship. [ABSTRACT FROM AUTHOR]

Background: Appropriate patient selection for simultaneous heart‐kidney transplantation (sHK) in patients with moderate renal dysfunction remains challenging. Methods: From the United Network for Organ Sharing database (2003–2020), we identified 5678 adults with an estimated pre‐transplant glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 and no pre‐transplant dialysis. Patients undergoing sHK (n = 293) were compared with those undergoing heart transplantation alone (n = 5385) using 1:3 propensity score matching. Results: The sHK utilization rate increased from 1.8% in 2003 to 12.2% in 2020 (p <.001). After matching, 1 and 5‐year survival was 87.7% (95% confidence interval [CI] 83.3–91.0) and 80.0% (95% CI 74.2–84.6) after sHK, and 87.3% (95% CI 85.2–89.1) and 71.8% (95% CI 68.4–74.9) after heart transplant alone (p =.04). In the subgroup analysis, sHK was associated with a 5‐year survival benefit only in patients with 30 < eGFR ≤ 35 mL/min/1.73 m2 (p =.05) but not in those with 35 < eGFR < 45 mL/min/1.73 m2 (p =.45). Patients who underwent heart transplants alone also had a higher incidence of becoming chronic dialysis‐dependent after transplant within 5‐year follow‐up (10.2%, 95% CI 8.0–12.6 vs. 3.8%, 95% CI 1.7–7.1, p =.004). The 5‐year incidence of subsequent kidney waitlisting and transplants after heart transplants alone was 5.6% and 1.9%, respectively. Conclusion: Among propensity‐matched patients without pre‐transplant dialysis, compared to heart transplants alone, sHK had improved 5‐year survival in those with 30 < eGFR ≤ 35 but not in those with 35 < eGFR < 45 mL/min/1.73 m2. One‐year survival was similar irrespective of eGFR. Receiving a kidney after a heart transplant alone is rare under the current allocation system. [ABSTRACT FROM AUTHOR]

The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p = 0. 045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0. 0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0. 05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p = 0. 24 and 0.79 respectively). Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes. [ABSTRACT FROM AUTHOR]

Objectives: There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure. Design: Retrospective cohort study. Setting: A large tertiary urban care center. Patients: Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022. Interventions: None. Measurements and Main Results: One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35–51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70–128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2–14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation. Conclusions: Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO 2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO 2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management. [ABSTRACT FROM AUTHOR]

Risk-adjusted survival after late heart re-transplantation may be comparable to primary transplant, but the efficacy of re-transplantation in older candidates is not established. We evaluated outcomes after heart re-transplantation in recipients > 60 years. We identified 1026 adult patients undergoing isolated heart re-transplantation between 2003 and 2020 from the United Network for Organ Sharing database. Older recipients (> 60 years, n=177) were compared to younger recipients (≤ 60 years, n=849). Five and ten-year post-transplant survival was estimated using the Kalpan-Meier method and adjusted with multivariable Cox models. Older recipients were more likely to be male and have diabetes or previous malignancies with higher baseline creatinine. They also more frequently required pre-transplant ECMO (11.9% vs. 6.8%, p =0.02) and received re-transplantation due to primary graft failure (13.6% vs. 8.5%, p =0.03). After the transplant, older recipients had a higher incidence of stroke (6.8% vs. 2.6%, p =0.01) and dialysis requirements (20.3% vs. 13.2%) before discharge (both p <0.05), and more frequently died from malignancy-related causes (16.3% vs. 3.9%, p <0.001). After adjustment, recipient age >60 was associated with an increased risk of both 5-year (HR 1.42, 95% CI 1.02-2.01, p =0.04) and 10-year mortality (HR 1.72, 95% CI 1.20-2.45, p =0.003). Restricted cubic spline showed a non-linear relationship between recipient age and 10-year mortality. Heart re-transplantation in recipients > 60 years has inferior outcomes compared to younger recipients. Strict patient selection and close follow-up are warranted to ensure the appropriate utilization of donor hearts and to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Shortage of organ donors is an ongoing limiting factor in lung transplantation (LT). Despite increasing prevalence of asymptomatic COVID-19 infection, positive COVID-19 testing from a potential donor remains a contraindication at many LT centers. In this report, we present the outcomes of LT utilizing an algorithm based on donor clinical presentation, and COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) with cycle threshold (Ct) values evaluation. The Ct value threshold for organ acceptance was >35. A total of 8 COVID-positive donors were included. No donor-to-recipient transmissions of COVID-19 were observed. Short-term outcomes were comparable to those reported in pre-COVID literature. Survival-to-date is 100% with median POD of 161 days. Our findings support the safety and efficacy of utilizing our algorithm including Ct value threshold for selection of donors with incidental COVID-19 positive testing. [Display omitted] [ABSTRACT FROM AUTHOR]

The article reports that study limitations include incomplete data on the duration of preoperative ventilatory or circulatory support and on preoperative Covid-19 tests and immunization. Topics include two negative bronchoalveolar lavages are required for lung-transplant eligibility; and short-term follow-up precludes firm conclusions about the longer-term usefulness of lung transplantation in context.

The number of lung transplant procedures performed internationally is increasing but the donor organ pool is insufficient to meet demand and waiting list mortality is unacceptably high. As survival rates for patients with acute respiratory distress syndrome managed on extracorporeal life support (ECLS) have steadily improved, a potential role for ECLS to support critically ill patients awaiting a donor organ match has emerged. We explore the rapidly evolving landscape of ECLS as a bridge to lung transplantation with review of the patient selection criteria, predictors of survival, modes of pre and peri-transplant support, and the importance of a holistic multidisciplinary approach to care. Finally, we consider innovations that are envisaged to increase the accessibility, safety, and effectiveness of ECLS delivery for future lung transplant candidates. [ABSTRACT FROM AUTHOR]

Background: Data are limited on outcomes after heart transplantation in patients bridged‐to‐transplantation (BTT) with a total artificial heart (TAH‐t). Methods: The UNOS database was used to identify 392 adult patients undergoing heart transplantation after TAH‐t BTT between 2005 and 2020. They were compared with 11 014 durable left ventricular assist device (LVAD) BTT patients and 22 348 de novo heart transplants (without any durable VAD or TAH‐t BTT) during the same period. Results: TAH‐t BTT patients had increased dialysis dependence compared to LVAD BTT and de novo transplants (24.7% vs. 2.7% vs. 3.8%) and higher levels of baseline creatinine and total bilirubin (all p <.001). After transplantation, TAH‐t BTT patients were more likely to die from multiorgan failure in the first year (25.0% vs. 16.1% vs. 16.1%, p =.04). Ten‐year survival was inferior in TAH‐t BTT patients (TAH‐t BTT 53.1%, LVAD BTT 61.8%, De Novo 62.6%, p <.001), while 10‐year survival conditional on 1‐year survival was similar (TAH‐t BTT 66.8%, LVAD BTT 68.7%, De Novo 69.0%, all p >.20). Among TAH‐t BTT patients, predictors of 1‐year mortality included higher baseline creatinine and total bilirubin, mechanical ventilation, and cumulative center volume <20 cases of heart transplantation involving TAH‐t BTT (all p <.05). Conclusion: Survival after TAH‐t BTT is acceptable, and patients who survive the early postoperative phase experience similar hazards of mortality over time compared to de novo transplant patients and durable LVAD BTT patients. [ABSTRACT FROM AUTHOR]

Heart transplantation remains limited by donor availability. Currently, only some programs accept older donors, and their use remains contentious. We compared outcomes of heart transplant recipients who received donor hearts ≥55 years with those who received donor hearts <55 years. Records of first-time adult heart transplant recipients between 2010 and 2019 were reviewed. Endpoints included 30-day and 1-, 3-, and 5-year survival; freedom from cardiac allograft vasculopathy; freedom from nonfatal major adverse cardiac events; and freedom from any rejections. The effect of donor age ≥55 years was analyzed with Cox proportional hazards modeling, 1:2 propensity score matching, and Kaplan-Meier survival analysis. Sixty-six patients received donor hearts ≥55 years and 766 received donor hearts <55 years. In the unmatched cohort, there was no significant difference in survival between the 2 groups at 30 days (93.9% vs 97.3%, P =.127), 1 year (87.9% vs 91.6%, P =.325), 3 years (86.4% vs 86.5%, P =.888), or 5 years (78.8% vs 83.8%, P =.497). The ≥55 years group had a significantly lower freedom from cardiac allograft vasculopathy and fatal major adverse cardiac events. In propensity-matched patients, recipients of donors ≥55 years had similar survival and freedom from cardiac allograft vasculopathy but significantly lower 1-year (76.7% vs 88.3%, P =.026), 3-year (68.3% vs 84.2%, P =.010), and 5-year (63.3% vs 83.3%, P =.002) freedom from nonfatal major adverse cardiac events when compared to recipients of younger donors. Carefully selected older donors can be considered for a carefully selected group of recipients with acceptable outcomes. [ABSTRACT FROM AUTHOR]

Ex-situ heart perfusion (ESHP) is commonly used for the reanimation and preservation of hearts following donation after circulatory determined death (DCD). The only commercially available existing ESHP device promotes perfusate lactate levels for assessment of heart viability. The reliability of this marker is yet to be confirmed for DCD heart transplantation. This is a single center, retrospective study examining DCD heart transplants from March 1, 2015 to June 30, 2020. Recipients were divided into 2 groups dependent upon their requirement for or absence of mechanical circulatory support post-transplant. Lactate profiles obtained during ESHP were analyzed. Hearts were procured using the direct procurement and perfusion (DPP) method. Fifty-one DCD heart transplant recipients were studied, of which 20 (39%) were dependent on mechanical circulatory support (MCS) following transplantation, (2% Ventricular Assist Device (VAD), 16% Extra Corporeal Membrane Oxygenation (ECMO) and 21% Intra-aortic balloon pumps (IABP). There was no difference in arterial lactate profiles on ESHP at any time point for those dependent upon MCS support (MCS) and those that were not (no MCS) post-transplant. After 3 hours of ESHP, the arterial lactate was >5mmol/L in 80% upon MCS vs 62% no MCS, p =.30. There was also no difference in ESHP rising arterial lactate concentrations, (15% MCS vs 13% non MCS, p = 1.00). For DCD hearts transplants retrieved using the DPP technique, lactate profiles do not seem to be a reliable predictor of mechanical circulatory support requirement post-transplant. [ABSTRACT FROM AUTHOR]

Introduction: The Organ Care System (OCS) is an ex vivo perfusion platform for donor heart preservation. Short/mid‐term post‐transplant outcomes after its use are comparable to standard cold storage (CS). We evaluated long‐term outcomes following its use. Methods: Between 2011 and 2013, 38 patients from a single center were randomized as a part of the PROCEED II trial to receive allografts preserved with CS (n = 19) or OCS (n = 19). Endpoints included 8‐year survival, survival free from graft‐related deaths, freedom from cardiac allograft vasculopathy (CAV), non‐fatal major adverse cardiac events (NF‐MACE), and rejections. Results: Eight‐year survival was 57.9% in the OCS group and 73.7% in the CS group (p =.24). Freedom from CAV was 89.5% in the OCS group and 67.8% in the CS group (p =.13). Freedom from NF‐MACE was 89.5% in the OCS group and 67.5% in the CS group (p =.14). Eight‐year survival free from graft‐related death was equivalent between the two groups (84.2% vs. 84.2%, p =.93). No differences in rejection episodes were observed (all p >.5). Conclusions: In select patients receiving OCS preserved allografts, late post‐transplant survival trended lower than those transplanted with an allograft preserved with CS. This is based on a small single‐center series, and larger numbers are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: A pressure overload model was developed to simulate aortic stenosis and assess caspase activity during the transition to heart failure. Background: Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure, and caspase activation is central to this pathophysiological process. Methods: A total of 10 sheep were banded with variable aortic constriction devices, progressively inflated to increase left ventricular (LV) afterload. Serial LV endomyocardial biopsy samples were obtained to measure caspase activity and presence of apoptosis. Results: Over the first 3 to 4 weeks, hypertrophy developed in the sheep (LV mass index 90.8 ± 4.9 g/m2 vs. 44.0 ± 3.0 g/m2, p < 0.01), followed by gradual dilatation of the left ventricle (diastolic LV internal diameter 4.23 ± 0.08 cm vs. 3.39 ± 0.07 cm, p < 0.01). Ventricular function remained stable until 7 to 8 weeks after banding, when there was significant deterioration (fractional shortening 18.3 ± 2.4% vs. 46.9 ± 2.6%, p < 0.01), associated with clinical heart failure. Serial LV endomyocardial biopsy samples were obtained at each echocardiographically defined stage (LV hypertrophy, LV dilation, and LV failure). Activity of caspases-3, -8, and -9 (measured by specific fluorogenic peptide substrates and immunohistochemistry) increased progressively, particularly with the onset of myocardial dysfunction (caspase-3 7.92 ± 1.19 vs. 1.00 ± 0.15, caspase-8 1.94 ± 0.21 vs. 1.00 ± 0.04, caspase-9 5.87 ± 0.97 vs. 1.00 ± 0.18 relative fluorescent units, p < 0.05). No evidence of deoxyribonucleic acid (DNA) fragmentation, however, was identified by immunohistochemical assays. Conclusions: Activation of cardiomyocyte caspase enzymes occurs during the transition to heart failure, without completion of apoptotic DNA fragmentation. Increased activity of caspase-8 and -9 suggests both mitochondrial and death-receptor mediated pathways are involved in this pathological process. Further knowledge of these pathways may stimulate development of apoptosis-based strategies for slowing progression of heart failure in aortic stenosis patients. [Copyright &y& Elsevier]

Predicted heart mass (PHM) equations have been proposed as an alternative method for size matching in heart transplantation. We assessed association between donor‐recipient size mismatch, defined using PHM equations, and survival post–heart transplant in the United Kingdom. Data from all adult patients who received a heart transplant between 1995 and 2017 were obtained from the United Kingdom Transplant Registry. PHM was calculated using published equations. Primary outcome was 1‐year survival post–heart transplantation. Recipients of undersized organs had reduced 1‐year survival (HR 1.31, 95% CI 1.03–1.67, p =.03). Oversizing had no impact on survival (HR 0.99, 95% CI 0.78–1.26, p =.96). Gender mismatching had no impact on survival in the cohort matched by PHM (HR 1.12, 95% CI 0.86–1.47, p =.4). In recipients without pulmonary hypertension, undersizing by PHM had no impact on 1‐year survival (HR 0.95, 95% CI 0.61–1.49, p =.83). In recipients with pulmonary hypertension, oversizing donor RV by using PHM RV equation (PHMRV) results in improved survival at 1 year (HR 0.65, 95% CI 0.5–0.83, p =.001). In conclusion, receiving an organ undersized by PHM was associated with decreased 1‐year survival. Subgroup analyses demonstrated that undersizing only impacted survival in recipients with pulmonary hypertension and that these recipients had improved outcomes if they received an organ with an RV oversized by >10% by PHMRV. [ABSTRACT FROM AUTHOR]

Combined heart–lung transplantation is the optimal treatment option for many patients with end-stage heart failure and fixed severe pulmonary hypertension. It offers the only possibility of long-term survival and a return to a normal quality of life. Unfortunately, it is rarely performed because of donor organ allocation policies. We present the case of a critically ill 24-year-old man, who after waiting for >100 days in-hospital on the urgent transplant list, deteriorated further and underwent the first successful heart–lung transplant with organs from a donation after circulatory death. [ABSTRACT FROM AUTHOR]

Central venoarterial extracorporeal membrane oxygenation has been used since the 1970s to support patients with cardiogenic shock following cardiac surgery. Despite this, in-hospital mortality is still high, and although rare, thrombus within the cardiac chambers or within the extracorporeal membrane oxygenation circuit is often fatal. Aprotinin is an antifibrinolytic available in Europe and Canada, though not currently in the United States. Due to historical safety concerns, use of aprotinin is generally limited and is commonly reserved for patients with the highest bleeding risk. Given the limited availability of aprotinin over the last decade, it is not surprising to find a complete absence of literature describing the use of venoarterial extracorporeal membrane oxygenation in the presence of aprotinin. We present three consecutive cases of rapid fatal intraoperative intracardiac thrombosis associated with post-cardiotomy central venoarterial extracorporeal membrane oxygenation in patients receiving aprotinin. [ABSTRACT FROM AUTHOR]

Background The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined. Objective Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF). Methods Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff. A controlled and progressive increase of LV pressure was monitored echocardiographically. Endomyocardial biopsies were collected throughout the development of LVF and subsequent recovery after pressure unloading. Results Thirteen sheep developed LVF with a subsequent recovery. Peak left ventricular hypertrophy (LVH) and dilatation (LVD) occurred at 31.5 ± 1.6 weeks and 102.7 ± 2.2 weeks post-banding respectively, with an increase in LV internal diameter in diastole (LVIDd 5.11 ± 0.12 compared to the control 3.37 ± 0.07 cm, p < 0.001), with preserved LV ejection fraction (LVEF). Reduced LVEF became evident 116.5 ± 2.7 weeks post-banding. Clinical and echocardiographic improvements were observed following deflation of the aortic banding cuff. By 138.1 ± 3.1 weeks cardiac performance recovered with restoration of LVEF. Significant changes in the expression of matrix metalloproteinases (MMP)-1, -2, -3, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF)-2, interferon (INF)-a-2 and soluble CD40 ligand (sCD40L) were observed throughout the progression to failure and recovery. Conclusions We used an ovine model to study reversible LV remodelling without interruption and found significant changes in matrixin and cardiokine expression during LV progression to failure and recovery. [ABSTRACT FROM AUTHOR]

The evidence base for size matching between donors and recipients in lung transplantation has not recently been reviewed in a comprehensive manner. Our aim in this study was to assimilate published studies that have addressed size matching of donors to recipients and to establish a pragmatic understanding of the range of lung sizes that may be used for lung transplantation. A comprehensive literature search was performed using Medline and PubMed up to and including September 2012, to identify scientific articles that relate to size matching between donors and lung transplant recipients. Seventy-two articles were identified, of which 21 had addressed the question of the impact of size mismatching on outcomes in lung transplantation. No study has specifically tested the consequences of intentionally mismatching above or below the hypothetical limits for double lung transplantation of a predicted total lung capacity for the donor of between 75% and 125% of the recipient predicted total lung capacity as set out in the ISHLT consensus report on lung donor acceptability criteria. Research is lacking that has robustly defined limits for size mismatch for single lung transplantation and for recipients with restrictive lung pathologies such as pulmonary fibrosis. Published research on the impact of size mismatching between lung transplant donors and recipients is limited by study design and size. It is centered on addressing the issue of mismatch in double lung transplantation in cohorts with a diagnostically heterogeneous make-up and in single lung transplant patients with chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES Raised pulmonary artery pressure (PAP), trans-pulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are risk factors for poor outcomes after heart transplant in patients with secondary pulmonary hypertension (PH) and may contraindicate transplant. Unloading of the left ventricle with an implantable left ventricular assist device (LVAD) may reverse these pulmonary vascular changes. We studied the effect of implanting centrifugal LVADs in a cohort of patients with secondary PH as a bridge to candidacy. METHODS Pulmonary haemodynamics on patients implanted with centrifugal LVADs at a single unit between May 2005 and December 2010 were retrospectively reviewed. RESULTS Twenty-nine patients were implanted with centrifugal LVADs (eight HeartWare ventricular assist device (HVAD), HeartWare International, USA and 21 VentrAssist, Ventracor Ltd., Australia). Seventeen were ineligible for transplant by virtue of high TPG/PVR. All the patients were optimized with inotrope/balloon pump followed by LVAD insertion. Four required temporary right VAD support. Thirty-day mortality post-LVAD was 3.4% (1 of 29) with a 1-year survival of 85.7% (24 of 28). Thirteen patients have been transplanted to date: 30-day mortality was 7.7% (1 of 13) and 1-year survival was 91% (10 of 11). Baseline and post-VAD pulmonary haemodynamics were significantly improved: systolic PAP (mmHg), mean PAP, TPG (mmHg) of 57 ± 9.5, 42 ± 4.4 and 14 ± 3.9 reduced to 32 ± 7.5, 18 ± 5.5 and 9 ± 3.3, respectively. PVR reduced from 5 ± 1.5 to 2.1 ± 0.5 Wood units (P < 0.05). CONCLUSIONS In selected heart failure patients with secondary PH, use of centrifugal LVAD results in significant reductions in PAP, TPG and PVR, which are observed within 1 month, reaching a nadir by 3 months. Such patients bridged to candidacy have post-transplant survival comparable with those having a heart transplant as primary treatment. [ABSTRACT FROM PUBLISHER]

Objective: Heart failure is now a public health epidemic. Donor hearts are severely restricted in availability. Permanent mechanical circulatory support or bridge to myocardial recovery are emerging alternatives. After extensive laboratory experience we sought to evaluate the intraventricular Jarvik 2000 Heart in patients with endstage heart failure. Methods: The Jarvik 2000 Heart is a novel thumb-sized left ventricular assist device (LVAD) which is fitted within the apex of the native left ventricle. A vascular graft off loads this to the descending thoracic aorta. The pump rotor spins at between 8000 and 12 000 rpm providing 5–6 litres blood flow per minute. We have used the device with skull-mounted power delivery for seven permanent implants and trans-abdominal drive line for ten bridge-to-transplant patients. Results: All patients survived the operation. Three died from non-device related complications. Survivors had early resolution of heart failure with return to NYHA I/II. All had pulsatile circulation. The device was user-friendly and imperceptible to the patient. Both the pump and native left ventricle contributed to the cardiac output during exercise. Seven patients have been transplanted successfully. All explanted devices were free from thrombus formation. Two permanent implant patients left hospital as early as 3 weeks postoperatively. Conclusions: The Jarvik 2000 is an effective user-friendly LVAD which allows early discharge from hospital. The intraventricular position has distinct advantages especially through absence of an inflow cannula. Synergy develops between the LVAD and native left ventricle. Early experience suggests that this may be a realistic LVAD to treat heart failure routinely in the outpatient setting. [Copyright &y& Elsevier]

SummaryBackground: Heart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure.Methods: As part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure.Findings: The Jarvik 2000 Heart sustained the patient's circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well.Conclusions: The initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability. [ABSTRACT FROM AUTHOR]