Journal: J Heart Lung Transplant

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Abstract

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

McGlothlin DP, Granton J, Klepetko W, Beghetti M, ... Zuckermann A, De Marco T
Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.

J Heart Lung Transplant: 01 Sep 2022; 41:1135-1194
McGlothlin DP, Granton J, Klepetko W, Beghetti M, ... Zuckermann A, De Marco T
J Heart Lung Transplant: 01 Sep 2022; 41:1135-1194 | PMID: 36123001
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Impact:
Abstract

Prolonged hospital length of stay after pediatric heart transplantation: A machine learning and logistic regression predictive model from the Pediatric Heart Transplant Society.

Gupta D, Bansal N, Jaeger BC, Cantor RC, ... Kirklin JK, Sutcliffe DL
Background
Heart transplantation (HT) is the gold standard for managing end-stage heart failure. Multiple quality metrics, including length of stay (LOS), have been used in solid organ transplantation. However, limited data are available regarding trends and factors influencing LOS after pediatric HT. We hypothesized that various donor, peri-transplant and recipient factors affect LOS after pediatric HT.
Methods
We analyzed patients <18years at time of HT from January 2005 to December 2018 in the Pediatric Heart Transplant Society database, and examined LOS trends, defined prolonged LOS (PLOS = LOS>30days after HT), identified factors associated with PLOS and assessed outcomes.
Results
Of 4827 patients undergoing HT, 4414 patients were discharged and included for analysis. Overall median LOS was 19days[13,34]. Median LOS was longer in patients with congenital heart disease(CHD = 25days[15,43] than with cardiomyopathy(CM = 17days[12,27] across all ages. Median LOS in age <1year was 26-days[16,45.5] and in age >10year was 16days[11,26]. PLOS was seen in 1313 patients(30%). Patients with PLOS were younger, smaller and had longer CPB times. There was no difference in utilization of VAD at HT between groups, however, ECMO use at listing(8.45% vs 2.93%,p < 0.05) and HT was higher in the PLOS group(9.22% vs 1.58%,p < 0.05). PLOS was more common in patients with previous surgery, CHD, single ventricle physiology, recipient history of cardiac arrest or CPR, end organ dysfunction, lower GFR, use of mechanical ventilation at HT and Status 1A at HT.
Conclusion
We present novel findings of LOS distribution and define PLOS after pediatric HT, providing a quality metric for individual programs to utilize and study in their practice.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 01 Sep 2022; 41:1248-1257
Gupta D, Bansal N, Jaeger BC, Cantor RC, ... Kirklin JK, Sutcliffe DL
J Heart Lung Transplant: 01 Sep 2022; 41:1248-1257 | PMID: 36123003
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Impact:
Abstract

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

Garry JD, Kolaitis NA, Kronmal R, Thenappan T, ... De Marco T, Pulmonary Hypertension Association Registry Investigators
Background
Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH.
Methods
The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL
Results:
Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09).
Conclusions
Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 Aug 2022; epub ahead of print
Garry JD, Kolaitis NA, Kronmal R, Thenappan T, ... De Marco T, Pulmonary Hypertension Association Registry Investigators
J Heart Lung Transplant: 28 Aug 2022; epub ahead of print | PMID: 36150996
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Abstract

The molecular features of chronic lung allograft dysfunction in lung transplant airway mucosa.

Halloran K, Mackova M, Parkes MD, Hirji A, ... Klepetko W, Halloran PF
Background
Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs.
Methods
We used genome-wide microarray measurements in 324 3BMBs to identify CLAD-selective changes as well as time-dependent changes and develop a CLAD classifier. CLAD-selective transcripts were identified with linear models for microarray data (limma) and were used to build an ensemble of 12 classifiers to predict CLAD. Hazard models and random forests were then used to predict the risk of graft loss using the CLAD classifier, transcript sets associated with rejection, injury, and time.
Results
T cell-mediated rejection and donor-specific antibody were increased in CLAD 3BMBs but most had no rejection. Like TBBs, 3BMBs showed a time-dependent increase in transcripts expressed in inflammatory cells that was not associated with CLAD or survival. Also like TBBs, the CLAD-selective transcripts in 3BMBs reflected severe parenchymal injury and dedifferentiation, not inflammation or rejection. While 3BMBs and TBBs did not overlap in their top 20 CLAD-selective transcripts, many CLAD-selective transcripts were significantly increased in both for example LOXL1, an enzyme controlling matrix remodeling. In Cox models for one-year survival, the 3BMB CLAD-selective transcripts and CLAD classifier predicted graft loss and correlated with CLAD stage. Many 3BMB CLAD-selective transcripts were also increased by injury in kidney transplants and correlated with decreased kidney survival, including LOXL1.
Conclusions
Mucosal and transbronchial biopsies from CLAD patients reveal a diffuse molecular injury and dedifferentiation state that impacts prognosis and correlates with the physiologic disturbances. CLAD state in lung transplants shares features with failing kidney transplants, indicating elements shared by the injury responses of distressed organs.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Aug 2022; epub ahead of print
Halloran K, Mackova M, Parkes MD, Hirji A, ... Klepetko W, Halloran PF
J Heart Lung Transplant: 27 Aug 2022; epub ahead of print | PMID: 36163162
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Impact:
Abstract

Model for screening adult congenital heart disease surgery eligibility with echocardiography parameters.

Zi-Yang Y, Hezhi L, Nanshan X, Yin Z, ... Hongwen F, Caojin Z
Objectives
This study aimed to screen for the eligibility of correction in cases of adult congenital heart disease (CHD). Pulmonary to systemic flow ratios (Qp/Qs) > 1.5 and pulmonary to systemic vascular resistance ratios (Rp/Rs) < 1/3, acquired by right heart catheterization (RHC), are two essential parameters. Nonetheless, performing RHC at every follow-up is impractical and even harmful. Thus, it is important to establish a model to predict Qp/Qs and Rp/Rs status before a RHC confirmation, using echocardiography parameters.
Methods
A total of 1,785 patients with adult CHD were enrolled and randomly assigned to the derivation or validation groups. Echocardiogram parameters of the 974 patients in the derivation group were considered candidate predictors for surgery eligibility (Qp/Qs > 1.5 and Rp/Rs < 1/3). Binary logistic regression analyses were performed to identify the independent predictors and establish a scoring system. The scoring system was further examined in the validation group using a receiver operating characteristic (ROC) analysis.
Results
Estimated pulmonary artery systolic pressure, velocity through the pulmonary valve, and diameters of the left and right atria were identified as independent predictors. The area under the ROC curve of the predictive value in the validation group and its pre- and post-tricuspid valve malformation subgroups were 0.87 (95% confidence interval [CI]: 0.84-0.90, p < 0.01), 0.86 (95% CI: 0.82-0.91, p < 0.01), and 0.85 (95% CI: 0.79-0.90, p < 0.01), respectively.
Conclusions
This scoring system could augment flexibility and convenience for pre-screening CHD patients\' eligibility for surgery, before RHC.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Aug 2022; epub ahead of print
Zi-Yang Y, Hezhi L, Nanshan X, Yin Z, ... Hongwen F, Caojin Z
J Heart Lung Transplant: 27 Aug 2022; epub ahead of print | PMID: 36150995
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Impact:
Abstract

The evaluation of constant coronary artery flow versus constant coronary perfusion pressure during normothermic ex situ heart perfusion.

Qi X, Hatami S, Bozso S, Buchko M, ... Nagendran J, Freed DH
Background
Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone.
Methods
Porcine hearts (n = 6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups.
Results
Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control = 8.33 vs pressure control = 6.46 mL·min-1·g-1, p = 0.016; edema formation: 7.92% vs 19.80%, p < 0.0001). Pro-inflammatory cytokines, platelet activation as well as endothelial activation were lower in the flow control group. Similarly, less cardiac and endothelial injury was observed in the constant coronary flow group. Evaluation of coronary artery function showed there was loss of coronary autoregulation in both groups. Oxidative stress was induced in the coronary arteries and was relatively lower in the flow control group.
Conclusions
A strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.

Copyright © 2022. Published by Elsevier Inc.

J Heart Lung Transplant: 20 Aug 2022; epub ahead of print
Qi X, Hatami S, Bozso S, Buchko M, ... Nagendran J, Freed DH
J Heart Lung Transplant: 20 Aug 2022; epub ahead of print | PMID: 36137869
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Impact:
Abstract

Contemporary risk scores predict clinical worsening in pulmonary arterial hypertension - An analysis of FREEDOM-EV.

Benza RL, Gomberg-Maitland M, Farber HW, Vizza CD, ... Rao Y, White RJ
Background
Risk scores integrate clinical variables emphasizing symptoms, exercise capacity, and measures of cardiac strain to predict clinical outcome better than any single value in pulmonary arterial hypertension (PAH). Risk scores have demonstrated prognostic utility for outcomes in registries, and recent studies have suggested that they are also therapy-responsive in controlled trials.
Methods
FREEDOM-EV, a global, placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo. Clinical assessments were performed every 12 weeks to calculate the non-invasive French risk assessment (FRA), 4-strata COMPERA, REVEAL 2.0, and REVEAL Lite 2; median follow-up was 58 weeks. The Week 12 risk scores were used to predict time to clinical worsening (from Week 12) with Kaplan-Meier product-limit estimates. Log-rank test was used to calculate the statistical difference among risk categories, and mediation analysis tested the hypothesis that improvements in risk score contributed to reduced likelihood for clinical worsening. We assessed the previously proposed \"net clinical benefit\" (achievement of FRA low-risk status and absence of clinical worsening).
Results
Both REVEAL scores, COMPERA, and FRA at Week 12 predicted subsequent clinical worsening better than baseline risk. Mediation analysis demonstrated that Week 12 risk score reduction explained part of TRE\'s effect on clinical worsening, especially for those with higher baseline risk. TRE assigned participants were more likely to achieve the previously proposed \"net clinical benefit\" at Weeks 24 and beyond. Few participants who achieved \'net clinical benefit\' had subsequent clinical worsening.
Conclusions
Contemporary risk scores were therapy responsive in FREEDOM-EV and early improvements predicted subsequent outcomes. This post hoc analysis suggests that risk scores may be a surrogate for clinical worsening.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 15 Aug 2022; epub ahead of print
Benza RL, Gomberg-Maitland M, Farber HW, Vizza CD, ... Rao Y, White RJ
J Heart Lung Transplant: 15 Aug 2022; epub ahead of print | PMID: 36117055
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Impact:
Abstract

Clinical impact of a modified lung allocation score that mitigates selection bias.

Schnellinger EM, Cantu E, Schaubel DE, Kimmel SE, Stephens-Shields AJ
Background
The Lung Allocation Score (LAS) is used in the U.S. to prioritize lung transplant candidates. Selection bias, induced by dependent censoring of waitlisted candidates and prediction of posttransplant survival among surviving, transplanted patients only, is only partially addressed by the LAS. Recently, a modified LAS (mLAS) was designed to mitigate such bias. Here, we estimate the clinical impact of replacing the LAS with the mLAS.
Methods
We considered lung transplant candidates waitlisted during 2016 and 2017. LAS and mLAS scores were computed for each registrant at each observed organ offer date; individuals were ranked accordingly. Patient characteristics associated with better priority under the mLAS were investigated via logistic regression and generalized linear mixed models. We also determined whether differences in rank were explained more by changes in predicted pre- or posttransplant survival. Simulations examined how 1-year waitlist, posttransplant, and overall survival might change under the mLAS.
Results
Diagnosis group, 6-minute walk distance, continuous mechanical ventilation, functional status, and age demonstrated the highest impact on differential allocation. Differences in rank were explained more by changes in predicted pretransplant survival than changes in predicted posttransplant survival, suggesting that selection bias has more impact on estimates of waitlist urgency. Simulations suggest that for every 1000 waitlisted individuals, 12.8 (interquartile range: 5.2-24.3) fewer waitlist deaths per year would occur under the mLAS, without compromising posttransplant and overall survival.
Conclusions
Implementing a mLAS that mitigates selection bias into clinical practice can lead to important differences in allocation and possibly modest improvement in waitlist survival.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 07 Aug 2022; epub ahead of print
Schnellinger EM, Cantu E, Schaubel DE, Kimmel SE, Stephens-Shields AJ
J Heart Lung Transplant: 07 Aug 2022; epub ahead of print | PMID: 36064649
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Impact:
Abstract

Clinical impact and economic burden of post-transplant infections following heart transplantation: A retrospective nationwide cohort study.

Jang SC, Oh BC, Nam JH, Lee EK, Kim HL, Kwon SH
Background
Post-transplant infections are associated with high mortality rates. This retrospective nationwide cohort study examined the incidence and risk factors of infections requiring hospitalization after heart transplantation and the associated economic burden.
Methods
The entire heart transplant recipients\' data from the Korean Health Insurance Review and Assessment Service between 2013 and 2020 was used. We estimated the annual incidence of post-transplant infections and adjusted incidence rate ratios (aIRR) of risk factors for reported infections using the poisson generalized linear model.
Results
Among 1,030 heart transplant recipients (324 with and 706 without post-transplant infections), 0.45 post-transplant infections were reported annually, with respiratory tract infections constituting the highest proportion (0.16). The risk of post-transplant infections was high in recipients with renal failure (aIRR = 1.35; 95% confidence interval [CI], 1.05-1.75) or nosocomial infection (aIRR = 1.47; 95% CI, 1.15-1.87). Combination regimens, including mammalian target of rapamycin inhibitor (mTORi), did not differ significantly from the standard 3 drug regimen (aIRR = 1.16; 95% CI, 0.80-1.67). The risk of death was higher among recipients with post-transplant infections than in uninfected recipients (adjusted hazard ratio = 4.59; 95% CI, 2.19-9.65). The mean follow-up cost per patient per month was 2-fold higher in recipients with post-transplant infections than in uninfected recipients ($5,096 and $2,532, respectively; p < .001).
Conclusions
mTORi combination, which reportedly maintains renal function, can be considered, as it does not increase the infection risk. Post-transplant infections present clinical and economic burdens, warranting careful observation of at-risk patients.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 06 Aug 2022; epub ahead of print
Jang SC, Oh BC, Nam JH, Lee EK, Kim HL, Kwon SH
J Heart Lung Transplant: 06 Aug 2022; epub ahead of print | PMID: 36088174
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Impact:
Abstract

Attitudes & practices surrounding pregnancy post heart transplant among pediatric providers.

Collins MM, Ou Z, Millar MM, Kittleson MM, ... Hayes KG, Lal AK
Background
Many pediatric heart transplant (HT) recipients reach adulthood and may be interested in family planning; there is little data regarding safety of pregnancy post HT and clinicians\' opinions differ. Pediatric HT clinicians are instrumental in early counseling. Thus, a better understanding of pediatric HT clinicians\' practices regarding family planning and how well aligned these practices are with adult transplant centers is essential.
Methods
We conducted a confidential, web-based survey of pediatric HT clinicians in fall 2021. We summarized and compared answers using Fisher\'s exact test.
Results
The survey was sent to 53 United States-based HT directors and to the International Society for Heart and Lung Transplantation and Pediatric Heart Transplant Society list serves. There were 69 respondents. The majority (77%) of respondents felt pregnancy was feasible in selected or all female HT recipients. Ten respondents reported that their institution had an established policy regarding pregnancy post HT. A majority (77%) of HT clinicians would either use a shared care model or recommend transition to their adult institution if pregnancy occurred, though 74% of respondents were either unaware of their corresponding adult institution\'s policy (62%) or had a counterpart adult program with a policy against pregnancy post HT (12%).
Conclusions
While many clinicians feel pregnancy is feasible in pediatric HT recipients, there remains significant practice variation. Few pediatric programs have a policy regarding pregnancy post HT. Future efforts to provide consistent messaging between adult and pediatric HT programs regarding the feasibility and care of post HT pregnancy are warranted.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jul 2022; epub ahead of print
Collins MM, Ou Z, Millar MM, Kittleson MM, ... Hayes KG, Lal AK
J Heart Lung Transplant: 30 Jul 2022; epub ahead of print | PMID: 36030149
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Impact:
Abstract

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

Koutsokera A, Sykes J, Theou O, Rockwood K, ... Stephenson AL, Singer LG
Background
Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes.
Methods
We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure.
Results
We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure.
Conclusions
In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 24 Jul 2022; epub ahead of print
Koutsokera A, Sykes J, Theou O, Rockwood K, ... Stephenson AL, Singer LG
J Heart Lung Transplant: 24 Jul 2022; epub ahead of print | PMID: 35970649
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Impact:
Abstract

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

Gulati G, Grandin EW, DeNofrio D, Upshaw JN, Vest AR, Kiernan MS
Background
While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined.
Methods
We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling.
Results
Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk.
Conclusions
Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 23 Jul 2022; epub ahead of print
Gulati G, Grandin EW, DeNofrio D, Upshaw JN, Vest AR, Kiernan MS
J Heart Lung Transplant: 23 Jul 2022; epub ahead of print | PMID: 35970648
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Impact:
Abstract

Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.

Huang J, Zhang R, Zhai K, Li J, ... Wu X, Li Y
Background
The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown.
Methods
We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated.
Results
VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response.
Conclusions
These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 23 Jul 2022; epub ahead of print
Huang J, Zhang R, Zhai K, Li J, ... Wu X, Li Y
J Heart Lung Transplant: 23 Jul 2022; epub ahead of print | PMID: 35973885
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Impact:
Abstract

Waitlist and post-transplant outcomes for children with myocarditis listed for heart transplantation over 3 decades.

Amdani S, Korang AA, Law Y, Cantor R, ... Bostdorff H, Joong A
Background
There is limited and conflicting information on waitlist and transplant outcomes for children with myocarditis.
Methods
Retrospective review included children with myocarditis and dilated cardiomyopathy (DCM) listed for HT from January 01, 1993 to December 31, 2019 in the Pediatric Heart Transplant Society database. Clinical characteristics, waitlist and post-HT outcomes (graft loss, rejection, cardiac allograft vasculopathy, infection and malignancy) for children listed from early (1993-2008) and current era (2009-2019) with myocarditis were evaluated and compared to those with DCM.
Results
Of 9755 children listed, 322 (3.3%) had myocarditis and 3178 (32.6%) DCM. Compared to DCM, children with myocarditis in the early and the current era were significantly more likely to be listed at higher urgency; be in intensive care unit; on mechanical ventilation; extracorporeal membrane oxygenation and ventricular assist device (p < 0.05 for all). While unadjusted analysis revealed lower transplant rates and higher waitlist mortality for children with myocarditis, in multivariable analysis, myocarditis was not a risk factor for waitlist mortality. Myocarditis, however, was a significant risk factor for early phase post-HT graft loss (HR 2.46; p = 0.003). Waitlist and post-HT survival for children with myocarditis were similar for those listed and transplanted in the early era to those listed and transplanted in the current era (p > 0.05 for both).
Conclusions
Children with myocarditis have a higher acuity of illness at listing and at HT and have inferior post-HT survival compared to children with DCM. Outcomes for children with myocarditis have not improved over the 3 decades and efforts are needed to improve outcomes for this cohort.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 21 Jul 2022; epub ahead of print
Amdani S, Korang AA, Law Y, Cantor R, ... Bostdorff H, Joong A
J Heart Lung Transplant: 21 Jul 2022; epub ahead of print | PMID: 36038480
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Impact:
Abstract

A comparison of outcomes after lung transplantation between European and North American centers.

Yang Z, Takahashi T, Terada Y, Meyers BF, ... Kreisel D, Puri V
Background
With advancements in basic science and clinical medicine, lung transplantation (LT) has evolved rapidly over the last three decades. However, it is unclear if significant regional variations exist in long-term outcomes after LT.
Methods
To investigate potential differences, we performed a retrospective, comparative cohort analysis of adult patients undergoing deceased donor single or double LT in North America (NA) or Europe between January 2006 and December 2016. Data up to April 2019 were abstracted from the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Registry. We compared overall survival (OS) between North American and European LT centers in a propensity score matched analysis.
Results
In 3,115 well-matched pairs, though 30-day survival was similar between groups (NA 96.2% vs Europe 95.4%, p = 0.116), 5-year survival was significantly higher in European patients (NA 60.1% vs Europe 70.3%, p < 0.001).
Conclusions
This survival difference persisted in a sensitivity analysis excluding Canadian patients. Prior observations suggest that these disparities are at least partly related to better access to care via universal healthcare models prevalent in Europe. Future studies are warranted to confirm our findings and explore other causal mechanisms. It is likely that potential solutions will require concerted efforts from healthcare providers and policymakers.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 21 Jul 2022; epub ahead of print
Yang Z, Takahashi T, Terada Y, Meyers BF, ... Kreisel D, Puri V
J Heart Lung Transplant: 21 Jul 2022; epub ahead of print | PMID: 35970646
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Impact:
Abstract

The effect of occlusive polytetrafluoroethylene outflow graft protectors in left ventricular assist device recipients.

Dimitrov K, Kaider A, Granegger M, Gross C, ... Laufer G, Zimpfer D
Background
The use of polytetrafluoroethylene (PTFE) material as a protective cover for left ventricular assist device (LVAD) outflow grafts (OG) is a common practice. However, it has descriptively been linked to the development of blood flow obstruction (BFO).
Methods
Patient data from 194 consecutive HVAD (Medtronic Inc; Medtronic, Minneapolis, MN) recipients implanted between March 2006 and January 2021 were retrospectively analyzed. PTFE covers were used in 102 patients. Study outcomes included the incidence of BFO and survival on LVAD support.
Results
Thirty-seven patients (19.1%) developed BFO during the study period. On a multivariable Cox regression analysis, PTFE use was an independent predictor for the development of BFO (HR 2.15, 95% CI 1.03-4.48, p = .04). BFO comprised of 2 types of device malfunction: eleven patients (5.7%) developed outflow graft stenosis (OGS), and 31 patients (16.0%) developed pump thrombosis (PT). There was a significantly higher cumulative incidence of OGS in patients with PTFE cover than in those without (Gray\'s test, p =.03). However, the observed higher cumulative incidence of PT in PTFE patients was non-significant (Gray\'s test, p =.06). In a multivariable Cox regression model, the effect of PTFE use on survival was non-significant (HR 0.95, 95% CI 0.60-1.48, p =.81), while the development of BFO was independently associated with increased mortality (HR 3.43, 95% CI 1.94-6.06, p < .0001).
Conclusions
The use of PTFE OG cover in LVAD patients is associated with an increased cumulative probability of development of BFO, the latter adversely impacting survival and is therefore, harmful.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 21 Jul 2022; epub ahead of print
Dimitrov K, Kaider A, Granegger M, Gross C, ... Laufer G, Zimpfer D
J Heart Lung Transplant: 21 Jul 2022; epub ahead of print | PMID: 36137868
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Impact:
Abstract

Textbook outcome in lung transplantation: Planned venoarterial extracorporeal membrane oxygenation versus off-pump support for patients without pulmonary hypertension.

Halpern SE, Wright MC, Madsen G, Chow B, ... Bottiger BA, Hartwig MG
Background
Planned venoarterial extracorporeal membrane oxygenation (VA ECMO) is increasingly used during bilateral orthotopic lung transplantation (BOLT) and may be superior to off-pump support for patients without pulmonary hypertension. In this single-institution study, we compared rates of textbook outcome between BOLTs performed with planned VA ECMO or off-pump support for recipients with no or mild pulmonary hypertension.
Methods
Patients with no or mild pulmonary hypertension who underwent isolated BOLT between 1/2017 and 2/2021 with planned off-pump or VA ECMO support were included. Textbook outcome was defined as freedom from intraoperative complication, 30-day reintervention, 30-day readmission, post-transplant length of stay >30 days, 90-day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, post-transplant ECMO, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Textbook outcome achievement was compared between groups using multivariable logistic regression.
Results
Two hundred thirty-seven BOLTs were included: 68 planned VA ECMO and 169 planned off-pump. 14 (20.6%) planned VA ECMO and 27 (16.0%) planned off-pump patients achieved textbook outcome. After adjustment for prior BOLT, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was associated with higher odds of textbook outcome than planned off-pump support (odds ratio 3.89, 95% confidence interval 1.58-9.90, p = 0.004).
Conclusions
At our institution, planned VA ECMO for isolated BOLT was associated with higher odds of textbook outcome than planned off-pump support among patients without pulmonary hypertension. Further investigation in a multi-institutional cohort is warranted to better elucidate the utility of this strategy.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 21 Jul 2022; epub ahead of print
Halpern SE, Wright MC, Madsen G, Chow B, ... Bottiger BA, Hartwig MG
J Heart Lung Transplant: 21 Jul 2022; epub ahead of print | PMID: 35961827
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Impact:
Abstract

Post-transplant diabetes mellitus following heart transplantation.

Newman JD, Schlendorf KH, Cox ZL, Zalawadiya SK, ... Shah RV, Lindenfeld J
Post-transplant diabetes mellitus (PTDM) is common following heart transplant, impacting greater than 20% of patients with most cases occurring in the first year after transplant. PTDM is associated with multiple negative sequelae including increased post-operative infections, a higher rate of renal failure, and increased mortality. Compared with pre-transplant diabetes mellitus, PTDM has several unique risk factors and immunosuppressive medications play an important role in disease pathophysiology. Newer treatments for hyperglycemia, including glucagon like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, may counter the mechanisms of immunosuppression-related hyperglycemia making them an appealing treatment option for patients with PTDM. Here, we review the definitions, incidence, risk factors, pathophysiology, clinical outcomes, treatment options, pharmacologic considerations, and future directions in PTDM.

Copyright © 2022. Published by Elsevier Inc.

J Heart Lung Transplant: 19 Jul 2022; epub ahead of print
Newman JD, Schlendorf KH, Cox ZL, Zalawadiya SK, ... Shah RV, Lindenfeld J
J Heart Lung Transplant: 19 Jul 2022; epub ahead of print | PMID: 35970647
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Impact:
Abstract

Hemodynamic reserve predicts early right heart failure after LVAD implantation.

Read JM, Azih NI, Peters CJ, Gurtu V, ... Birati EY, Tedford RJ
Background
Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve.
Methods
We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium.
Results
Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/m2; p < 0.001; AUC: 0.78; optimal cut-point: 22.1 mL/m2) during nitroprusside administration. Multivariable analysis revealed that peak SVI was significantly associated with early RHF, demonstrating a 16% increase in risk of early RHF per 1 ml/m2 decrease in SVI. A follow up cohort of 10 consecutive patients from July 2020 to October 2021 resulted in all patients being categorized appropriately in regards to early RHF versus no RHF according to peak SVI.
Conclusion
Peak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 16 Jul 2022; epub ahead of print
Read JM, Azih NI, Peters CJ, Gurtu V, ... Birati EY, Tedford RJ
J Heart Lung Transplant: 16 Jul 2022; epub ahead of print | PMID: 35934606
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Impact:
Abstract

Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients.

Gallais F, Renaud-Picard B, Solis M, Laugel E, ... Kessler R, Fafi-Kremer S
Background
Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors.
Methods
A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression.
Results
After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 log10 copies/mL before vaccination (Odds Ratio (OR) = 17.87, 95% confidence interval (CI95) = 3.02-105.72), mycophenolate treatment (OR = 4.73, CI95 = 1.46-15.34) and BNT162b2 (n = 34; vs mRNA-1273, n = 101) vaccine (OR = 6.72, CI95 = 1.75-25.92). In second dose non-responders, TTV VL ≥6.2 or <3.2 log10 copies/mL before the third dose was associated with low (0/19) and high (9/10) rates of seroconversion.
Conclusion
COVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 16 Jul 2022; epub ahead of print
Gallais F, Renaud-Picard B, Solis M, Laugel E, ... Kessler R, Fafi-Kremer S
J Heart Lung Transplant: 16 Jul 2022; epub ahead of print | PMID: 35953352
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Impact:
Abstract

Biology of myocardial recovery in advanced heart failure with long-term mechanical support.

Tseliou E, Lavine KJ, Wever-Pinzon O, Topkara VK, ... Burkhoff D, Drakos SG
Cardiac remodeling is an adaptive, compensatory biological process following an initial insult to the myocardium that gradually becomes maladaptive and causes clinical deterioration and chronic heart failure (HF). This biological process involves several pathophysiological adaptations at the genetic, molecular, cellular, and tissue levels. A growing body of clinical and translational investigations demonstrated that cardiac remodeling and chronic HF does not invariably result in a static, end-stage phenotype but can be at least partially reversed. One of the paradigms which shed some additional light on the breadth and limits of myocardial elasticity and plasticity is long term mechanical circulatory support (MCS) in advanced HF pediatric and adult patients. MCS by providing (a) ventricular mechanical unloading and (b) effective hemodynamic support to the periphery results in functional, structural, cellular and molecular changes, known as cardiac reverse remodeling. Herein, we analyze and synthesize the advances in our understanding of the biology of MCS-mediated reverse remodeling and myocardial recovery. The MCS investigational setting offers access to human tissue, providing an unparalleled opportunity in cardiovascular medicine to perform in-depth characterizations of myocardial biology and the associated molecular, cellular, and structural recovery signatures. These human tissue findings have triggered and effectively fueled a \"bedside to bench and back\" approach through a variety of knockout, inhibition or overexpression mechanistic investigations in vitro and in vivo using small animal models. These follow-up translational and basic science studies leveraging human tissue findings have unveiled mechanistic myocardial recovery pathways which are currently undergoing further testing for potential therapeutic drug development. Essentially, the field is advancing by extending the lessons learned from the MCS cardiac recovery investigational setting to develop therapies applicable to the greater, not end-stage, HF population. This review article focuses on the biological aspects of the MCS-mediated myocardial recovery and together with its companion review article, focused on the clinical aspects, they aim to provide a useful framework for clinicians and investigators.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 16 Jul 2022; epub ahead of print
Tseliou E, Lavine KJ, Wever-Pinzon O, Topkara VK, ... Burkhoff D, Drakos SG
J Heart Lung Transplant: 16 Jul 2022; epub ahead of print | PMID: 35965183
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Impact:
Abstract

Left ventricular assist device implantation via lateral thoracotomy: A systematic review and meta-analysis.

Ribeiro RVP, Lee J, Elbatarny M, Friedrich JO, ... Yanagawa B, Canadian Cardiovascular Surgery Meta-Analysis Working Group
Background
Left ventricular assist device (LVAD) implantation via lateral thoracotomy can offer similar effectiveness to conventional approaches with less perioperative adverse events. We performed a systematic review and meta-analysis to determine the potential benefits of lateral thoracotomy (LT) for LVAD implantation compared to median sternotomy.
Methods
We searched MEDLINE and Embase databases for studies comparing continuous-flow LVAD implantation using LT with conventional sternotomy. Main outcomes were perioperative mortality and complications.
Results
Twenty-five observational studies enrolling 3072 patients were included with a median follow-up of 10 months. Perioperative mortality (30 day or in-hospital) was 7% (LT) and 14% (sternotomy); however, mortality differences were no longer statistically significant in matched/adjusted studies (RR:0.86; 95%CI:0.52-1.44; p = 0.58). LT was associated with decreased need for blood product transfusions (mean difference[MD]: -4.7; 95%CI: -7.2 to -2.3 units; p < 0.001), reoperation for bleeding (RR:0.34; 95%CI:0.22-0.54; p < 0.001), postoperative RVAD implantation (RR:0.53; 95%CI:0.36-0.77; p < 0.001), days requiring inotropes (MD: -1.1; 95%CI: -2.1 to -0.03 inotrope days; p = 0.04), ICU (MD: -3.3; 95%CI: -6.0 to -0.7 ICU days; p = 0.01), and hospital length of stay (MD: -5.1; 95%CI: -10.1 to -0.1 hospital days; p = 0.04) in matched/adjusted studies. Overall mortality during follow-up was significantly lower for LT in unmatched/unadjusted studies but not statistically significantly lower in matched/adjusted studies (Hazard Ratio:0.82; 95%CI:0.59-1.14; p = 0.24).
Conclusion
LVAD implantation via LT was associated with significantly decreased need for blood products, reoperation for bleeding, and postoperative RVAD implantation. Furthermore, days on inotropic support were also lower, likely contributing to the shorter length of stay. These findings support greater use of a LT approach for carefully selected patients.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 Jul 2022; epub ahead of print
Ribeiro RVP, Lee J, Elbatarny M, Friedrich JO, ... Yanagawa B, Canadian Cardiovascular Surgery Meta-Analysis Working Group
J Heart Lung Transplant: 11 Jul 2022; epub ahead of print | PMID: 35953353
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Impact:
Abstract

Incompleteness of health-related quality of life assessments before left ventricular assist device implant: A novel quality metric.

Yang G, Zhang M, Zhou S, Hou H, ... Likosky DS, Michigan Congestive Heart Failure Investigators
Background
Improved health-related quality of life (HRQOL) is an important outcome following durable left ventricular assist device (LVAD) implant. However, half of pre-implant HRQOL data are incomplete in The Society of Thoracic Surgeons\' Intermacs registry. Pre-implant HRQOL incompleteness may reflect patient status or hospital resources to capture HRQOL data. We hypothesized that pre-implant HRQOL incompleteness predicts 90 day outcomes and serves as a novel quality metric.
Methods
Risk factors for pre-implant HRQOL (EQ-5D-5L visual analog scale; 12-item Kansas City Cardiomyopathy Questionnaire \"KCCQ\") incompleteness were examined by stepwise logistic modeling. Direct standardization method was used to calculate adjusted incompleteness rates using a mixed effects logistic model. Hospitals were dichotomized as low or high based on median adjusted incompleteness rates. Andersen-Gill models were used to associate pre-implant HRQOL adjusted incompleteness rate with adverse events within 90 day post-implant.
Results
The study cohort included 14,063 patients receiving a primary LVAD (4/2012-8/2017). HRQOL incompleteness at high-rate hospitals was more often due to administrative reasons (risk difference, EQ-5D: 10.1%; KCCQ-12: 11.6%) and less likely due to patient reasons (risk difference, EQ-5D: -8.9%; KCCQ-12: -11.4%). A 10% increase in the adjusted pre-implant EQ-5D incompleteness rate was significantly associated with higher risk of infection-related mortality (HR: 1.09), infection (HR: 1.05), and renal dysfunction (HR: 1.03). A 10% increase in the adjusted pre-implant KCCQ-12 incompleteness rate was significantly associated with higher risk of infection (HR: 1.04).
Conclusions
Hospital adjusted pre-implant HRQOL incompleteness was predictive of 90-day post-implant outcomes and may serve as a novel quality metric.

Copyright © 2022. Published by Elsevier Inc.

J Heart Lung Transplant: 08 Jul 2022; epub ahead of print
Yang G, Zhang M, Zhou S, Hou H, ... Likosky DS, Michigan Congestive Heart Failure Investigators
J Heart Lung Transplant: 08 Jul 2022; epub ahead of print | PMID: 35961829
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Impact:
Abstract

Eplet matching in pediatric heart transplantation: The SickKids experience.

Cardoso B, Wang J, Kiernan J, Dipchand AI
Background
Epitope-based tissue matching may be superior to HLA antigen matching. We compared antigen to molecular-level HLA matching on outcomes following pediatric heart transplantation (HTx).
Methods
This is a retrospective, single centre cohort study (2013-2020). HLA antigen and eplet mismatch analyses were performed in HTx patients <18 years old. Primary endpoint was graft loss; secondary endpoints were rejection and cardiac allograft vasculopathy (CAV). A multivariable Cox regression analysis was used to examine associations between eplet or antigen mismatching and outcomes. A logistic regression analysis was performed to examine associations between eplet or antigen mismatching and outcomes.
Results
Seventy-seven patients (40% males) were included, with a median age at HTx 4.3 years [range 0.05-18]. Median HLA class I and II eplet mismatches were 10 (1-22) and 11 (1-23). Median class I and II antigen mismatches were 5 (1-6) and 4 (0-6). 9 patients (11.7%) died [median time 4 months (range 0.1-46)]. Eight (10.4%) patients developed AMR [median time 22 days (IQR = 168)]. Twenty-one patients (27.3%) had acute cellular rejection [median time 40 days (IQR = 85.5)]. In univariate analysis, patients with HLA Class II DPB eplet mismatches above the median for this cohort had an increased risk of graft loss (OR 5.3 [95%CI: 1.03-27.5], p = 0.039). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with either graft loss or rejection. In multivariable analysis, patients with HLA Class II DPB eplet mismatches above the median had an increased risk of graft loss (HR 8.14 [95% CI: 1.26-49], p = 0.02). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with graft loss or rejection. A logistic regression analysis including \'number of HLA Class II DPB eplet mismatches\' correctly predicted 95.8% of the outcomes.
Conclusion
In our cohort of pediatric heart transplant recipients, the number of HLA Class II DPB eplet mismatches was associated with graft loss. Molecular-level HLA matching is an emerging tool for graft loss risk stratification, but further study is required.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 05 Jul 2022; epub ahead of print
Cardoso B, Wang J, Kiernan J, Dipchand AI
J Heart Lung Transplant: 05 Jul 2022; epub ahead of print | PMID: 35933296
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Impact:
Abstract

Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry.

Harhay MO, Cherikh WS, Toll AE, Christie JD, ... Hayes D, Cantu E
Background
Lung retransplantation is a complex surgical decision that represents the only potential treatment option for recipients suffering from lung allograft failure. We sought to describe the modern landscape of lung retransplantation and to compare the relative importance of selected clinical, donor, and recipient factors on mortality in the year following lung retransplantation.
Methods
We conducted a retrospective cohort study of first-time adult recipients of deceased donor lung retransplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 2005 through June 2017. In addition to describing the characteristics of lung retransplant recipients, we examined 1 year survival overall, and by initial transplant-retransplant procedure type, recipient age, retransplant indication, and time-to-lung retransplantation (i.e., inter-transplant interval). We used the Somers\' Dxy rank correlation statistic for censored data to assess the relative importance of several potential prognostic risk factors for mortality in the year following lung retransplantation.
Results
Our cohort included 1,597 lung retransplant recipients. 2005 was the first year with more than 100 retransplants, and since 2007, 138 to 188 retransplants (approximately 4%-6% of all transplants) were reported annually to the ISHLT Registry. The median inter-transplant interval was 3.4 years (interquartile range: 1.6-6.2 years). Forty-three percent of the cohort had an obliterative bronchiolitis retransplant indication, whereas 17% had primary graft failure. One-third (32%) were retransplanted within 2 years of their primary transplant, and 64% received a double lung transplant both times, whereas 36% received consecutive single lung transplants. Six-month and 1 year survival (82% and 76%) were higher for double-double lung retransplant recipients than for single-single recipients (76% and 69%). The 3 strongest prognostic factors for 1 year mortality were the inter-transplant interval (decreasing hazard with longer intervals), donor age (increasing hazard with older age), and need for mechanical ventilation preceding lung retransplantation.
Conclusions
Retransplants comprise approximately 5% of annual lung transplants worldwide. The factor most strongly associated with 1 year mortality in this population was the duration of time since the primary lung transplant, with a persistent reduction in risk as more time elapses.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 05 Jul 2022; epub ahead of print
Harhay MO, Cherikh WS, Toll AE, Christie JD, ... Hayes D, Cantu E
J Heart Lung Transplant: 05 Jul 2022; epub ahead of print | PMID: 35933297
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Impact:
Abstract

Lung allograft standardized histological analysis (LASHA) template: A research consensus proposal.

Calabrese F, Roden AC, Pavlisko E, Lunardi F, ... Levine DJ, Roux A
Background
Routine monitoring of lung-transplanted patients is crucial for the identification of immunological and non-immunological complications. Determining the etiology of acute allograft dysfunction, particularly in alloimmune-mediated disorders, relies heavily on the lung biopsy with histopathologic analysis. Standardization of the pathologic diagnosis of rejection (e.g., cellular and antibody-mediated) is based on consensus statements and guidelines, indicating the importance of a multidisciplinary approach to achieve a definitive etiological diagnosis. In addition to these statements and guidelines, refinements and standardizations are feasible through systematic analysis morphological, immunophenotypic and molecular alterations observed in transbronchial biopsies. This study is to identify key morphologic features to be assessed, select consistent and reproducible terminology for each histological feature, and provide standardized definitions for pathological assessment and grading.
Methods
A template was created by experts in lung transplantation including pathologists, pulmonologists, immunologists. An initial draft was circulated, followed by discussions and multiple revisions by email and conference calls.
Results
The \"lung allograft standardized histological analysis - LASHA\" template was created and structured as multiple-choice questions with number of fields to be filled in to allow for standardization of results and easy transfer into a future electronic spreadsheet.
Conclusion
This template will help facilitate multicenter studies through a uniform protocol and correlations with new diagnostic modalities. After validation in large-scale studies, an optimized template could be included in routine clinical practice to enhance graft assessment and medical decision-making.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 03 Jul 2022; epub ahead of print
Calabrese F, Roden AC, Pavlisko E, Lunardi F, ... Levine DJ, Roux A
J Heart Lung Transplant: 03 Jul 2022; epub ahead of print | PMID: 35931644
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Impact:
Abstract

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS.

Schwarz S, Lang C, Harlander M, Štupnik T, ... Jaksch P, Hoetzenecker K
Background
Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown.
Methods
This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis.
Results
A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the \'SSC\' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of \'SSC\' patients was severely impaired compared to \'no SSC\' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004).
Conclusions
SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 02 Jul 2022; epub ahead of print
Schwarz S, Lang C, Harlander M, Štupnik T, ... Jaksch P, Hoetzenecker K
J Heart Lung Transplant: 02 Jul 2022; epub ahead of print | PMID: 35907758
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Impact:
Abstract

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases.

Eichenberger EM, Coniglio AC, Milano C, Schroder J, ... Reynolds J, Wolfe CR
We present our institution\'s protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.

Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jun 2022; epub ahead of print
Eichenberger EM, Coniglio AC, Milano C, Schroder J, ... Reynolds J, Wolfe CR
J Heart Lung Transplant: 30 Jun 2022; epub ahead of print | PMID: 35871114
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Impact:

This program is still in alpha version.