Journal: J Heart Lung Transplant

Sorted by: date / impact
Abstract

Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

Hug KP, Gerry Coghlan J, Cannon J, Taboada D, ... Pepke-Zaba J, Hoole SP
Background
Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome.
Methods
Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response.
Results
Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson\'s r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate.
Conclusions
The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jun 2021; epub ahead of print
Hug KP, Gerry Coghlan J, Cannon J, Taboada D, ... Pepke-Zaba J, Hoole SP
J Heart Lung Transplant: 30 Jun 2021; epub ahead of print | PMID: 34303575
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association between digoxin use and gastrointestinal bleeding in contemporary continuous flow left ventricular assist device support.

El Rafei A, Trachtenberg BH, Schultz J, John R, ... Goodwin K, Cogswell R
Background
Assess the association between digoxin use and gastrointestinal bleeding (GIB) in a multicenter continuous flow left ventricular assist device (LVAD) cohort.
Methods
Patients implanted with continuous flow LVADs with data on GIB and digoxin use from two centers were included in the analysis (n = 649). GIB events were captured up to 2 years of follow-up. Digoxin use was defined as digoxin prescribed at discharge or within the first 3 months after LVAD implantation. A negative binomial regression model was performed to determine the association between digoxin use and number of GIB events over the follow-up period.
Results
Mean age of the cohort was 57 years (±14) and 45% (293/649) were bridge to transplant (BTT). Digoxin was prescribed in 33% of patients. Digoxin use was associated with an unadjusted 32% reduction in the incidence of rate of all cause GIB (IRR 0.68, 95% CI 0.46-0.99, p = 0.049). After adjusting for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, renal function, and implanting center there was still a 34% reduction in the incidence rate (IRR 0.67, 95% CI 0.45-0.99, p = 0.048). When limiting the analysis to those with likely arteriovenous malformation associated GIB, the association strengthened (unadjusted: IRR 0.48, 95 % CI 0.26-0.89, p = 0.02, adjusted: IRR 0.47, 95 % CI 0.25-0.9, p = 0.022).
Conclusions
In this multicenter study, inclusive of contemporary devices, digoxin use was associated with reduced GIB events. Prospective data will be required to confirm this association.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 29 Jun 2021; 40:671-676
El Rafei A, Trachtenberg BH, Schultz J, John R, ... Goodwin K, Cogswell R
J Heart Lung Transplant: 29 Jun 2021; 40:671-676 | PMID: 33875331
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score.

Sage AT, Richard-Greenblatt M, Zhong K, Bai XH, ... Kain KC, Keshavjee S
Background
Ex vivo lung perfusion (EVLP) is an isolated organ assessment technique that has revolutionized the field of lung transplantation and enabled a safe increase in the number of organs transplanted. The objective of this study was to develop a protein-based assay that would provide a precision medicine approach to lung injury assessment during EVLP.
Methods
Perfusate samples collected from clinical EVLP cases performed from 2009 to 2019 were separated into development (n = 281) and validation (n = 57) sets to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in perfusate. The ability of an inflammation score to predict lungs suitable for transplantation and likely to produce excellent recipient outcomes (time on ventilator ≤ 3 days) was assessed. Inflammation scores were compared to conventional clinical EVLP assessment parameters and associated with outcomes, including primary graft dysfunction and patient care in the ICU.
Results
An inflammation score accurately predicted the decision to transplant (AUROC 68% [95% CI 62-74]) at the end of EVLP and those transplants associated with short ventilator times (AUROC 73% [95% CI 66-80]). The score identified lungs more likely to develop primary graft dysfunction at 72-hours post-transplant (OR 4.0, p = 0.03). A model comprised of the inflammation score and ∆PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87% [95% CI 83-92].
Conclusions
The adoption of an inflammation score will improve accuracy of EVLP decision-making and increase confidence of surgical teams to determine lungs that are suitable for transplantation, thereby improving organ utilization rates and patient outcomes.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 29 Jun 2021; 40:687-695
Sage AT, Richard-Greenblatt M, Zhong K, Bai XH, ... Kain KC, Keshavjee S
J Heart Lung Transplant: 29 Jun 2021; 40:687-695 | PMID: 33781664
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates.

Sriwattanakomen R, Xu Q, Demehin M, Shullo MA, ... Keebler ME, Zeevi A
Background
Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis.
Methods
One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16. Patients underwent repeat cycles as indicated. We compare calculated panel-reactive antibody (cPRA) for neat combined Class I and II IgG and C1q pre- and post-treatment using a cutoff for cPRA entry of ≥ 4000 and 500 MFI, respectively.
Results
From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving.
Conclusions
A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:595-603
Sriwattanakomen R, Xu Q, Demehin M, Shullo MA, ... Keebler ME, Zeevi A
J Heart Lung Transplant: 29 Jun 2021; 40:595-603 | PMID: 33785250
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Stroke in pediatric ventricular assist device patients-a pedimacs registry analysis.

Niebler RA, Amdani S, Blume B, Cantor RS, ... Rosenthal DN, Ghanayem NS
Background
Cerebralvascular accidents (CVA) are common complications of pediatric ventricular assist devices (VADs). We employed the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) to investigate rates, risk factors, and outcomes of CVA in pediatric patients supported on VAD.
Methods
Analysis of Pedimacs (September 2012-June 2019) data to determine rates of all neurologic events and specifically CVA. Risk factors were determined by a multiphase parametric hazard model. Outcomes of patients with CVA were compared with patients without CVA.
Results
We included 662 patients in our analysis. In total, 87 CVA events occurred in 71 patients (10.7%). The proportion of patients with CVA was highest in the paracorporeal pulsatile group (16.9%) followed by the paracorporeal continuous group (10.4%). However, the rate of CVA was lower in the paracorporeal pulsatile group compared to the paracorporeal continuous group (6.4 vs 11.1 events/100 patient months), which reflects differences in support duration. Ascites, higher patient profile groups, and implants within small volume centers were associated with the occurrence of CVA. Our analysis found that the recent era (i.e., June 2017), and intracorporeal continuous implants were protective. Mortality was higher in patients following a CVA diagnosis compared to those without a CVA diagnosis.
Conclusions
CVA continues to be a problem in pediatric VAD support, though the overall percent is now <11%. Data from the most recent era are encouraging, but CVA is still significantly associated with mortality. Future efforts should focus on pre-implant and early support periods.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:662-670
Niebler RA, Amdani S, Blume B, Cantor RS, ... Rosenthal DN, Ghanayem NS
J Heart Lung Transplant: 29 Jun 2021; 40:662-670 | PMID: 33824064
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart transplant in Jehovah\'s Witness patients: A case-control study.

Sander S, Singer-Englar T, Nishihara K, Esmailian F, ... Kobashigawa JA, Kittleson MM
Heart transplantation (HTx) improves quality of life and survival in patients with advanced heart failure. Jehovah\'s Witnesses (JW) patients decline blood transfusion (including red cells, plasma and platelets) and are prohibited from heart transplantation at many centers. We report our experience with 20 consecutive JW patients with advanced heart failure who declined blood products referred to our center for HTx consideration. Of these, 7 were declined for transplant due to prior sternotomy, need for multi-organ transplant, or being too well. Of 13 JW patients accepted for heart transplant listing, 8 underwent HTx at our center. Compared to non-JW controls without prior cardiac surgery matched for age and listing status, JW HTx recipients had comparable incidence of primary graft dysfunction, rejection, allograft vasculopathy, and survival and hemoglobin up to 1 year. With appropriate selection, patients who are JW and decline blood products may successfully undergo heart transplantation.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:575-579
Sander S, Singer-Englar T, Nishihara K, Esmailian F, ... Kobashigawa JA, Kittleson MM
J Heart Lung Transplant: 29 Jun 2021; 40:575-579 | PMID: 33839007
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lung and heart-lung transplantation for children with PAH: Dramatic benefits from the implementation of a high-priority allocation program in France.

Le Pavec J, Séverine F, Olaf M, Pauline P, ... Marc H, Elie F
Purpose
Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx.
Methods
We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively.
Results
Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; p = 0.02).
Conclusion
HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:652-661
Le Pavec J, Séverine F, Olaf M, Pauline P, ... Marc H, Elie F
J Heart Lung Transplant: 29 Jun 2021; 40:652-661 | PMID: 33849770
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Factors contributing to exercise capacity in chronic thromboembolic pulmonary hypertension with near-normal hemodynamics.

Tobita K, Goda A, Nishida Y, Takeuchi K, ... Soejima K, Satoh T
Background
Despite improved survival for patients with chronic thromboembolic pulmonary hypertension (CTEPH) due to progressive medical and interventional treatment, impaired exercise capacity remains common due to poorly understood mechanisms. We aimed to clarify the exercise capacity of CTEPH patients with near-normal pulmonary hemodynamics and evaluate its determinants among the hemodynamic, peripheral (e.g., oxygen use by the peripheral tissues), and muscular (e.g., skeletal muscle strength) factors.
Methods
Three hundred and twenty-nine patients with CTEPH (mean age, 63 ± 12 years; men/women, 73/256) with a near-normal mean pulmonary artery pressure (≤30 mm Hg) at rest were enrolled. We assessed exercise capacity by peak oxygen consumption (peak VO2) using cardiopulmonary exercise testing with a right heart catheter. We also measured the 6-minute walk distance (6MWD) and quadriceps muscle strength.
Results
The mean pulmonary artery pressure was 19 ± 4 mmHg and mean cardiac output was 4.8 ± 1.5 L/min at rest. The mean 6MWD was 444 ± 101 m, while the mean peak VO2 was 14.4 ± 3.9 mL/min/kg. A multivariate model that predicted 6MWD included quadriceps strength (β = 0.45, p < 0.001) and peak arterial venous oxygen difference (β = 0.29, p < 0.001). In contrast, the peak VO2 was best correlated with mPAP-CO slope (β = -0.30, p < 0.001), followed by quadriceps strength and peak arterial venous oxygen difference.
Conclusions
The 6MWD performance may be significantly influenced by peripheral oxygen use and muscular factors, while peak VO2 is influenced by hemodynamic and peripheral factors in CTEPH patients with near-normal hemodynamics.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 29 Jun 2021; 40:677-686
Tobita K, Goda A, Nishida Y, Takeuchi K, ... Soejima K, Satoh T
J Heart Lung Transplant: 29 Jun 2021; 40:677-686 | PMID: 33879384
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Percutaneous RVAD with the Protek Duo for severe right ventricular primary graft dysfunction after heart transplant.

Carrozzini M, Merlanti B, Olivieri GM, Lanfranconi M, ... Mondino M, Russo CF
Right ventricular primary graft dysfunction after heart transplant is a serious life-threatening condition. The severe form, refractory to maximal medical therapy, has traditionally required temporary mechanical support through veno-arterial extracorporeal membrane oxygenation or central right ventricular support. The Protek Duo is a dual lumen cannula recently introduced in the market, which allows for the institution of a percutaneous right ventricular support. We present the first promising case series of the use of this novel support in patients with right ventricular primary graft dysfunction after heart transplant.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:580-583
Carrozzini M, Merlanti B, Olivieri GM, Lanfranconi M, ... Mondino M, Russo CF
J Heart Lung Transplant: 29 Jun 2021; 40:580-583 | PMID: 33879383
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Kinetics of generic tacrolimus in heart transplantation: A cautionary note.

Il\'Giovine ZJ, Williams JB, Mason RP, Sherratt SCR, ... Mehra MR, Starling RC
Tacrolimus is a core component of immunosuppressive regimens. This study compared active pharmaceutical ingredient (API) and dissolution kinetics of branded tacrolimus and formulations from three generic manufacturers (Mylan, Dr. Reddy\'s, Intas) including samples from patients who suffered acute cardiac allograft rejection. Generic samples showed similar API content compared to branded samples with no major impurities. Capsules that underwent uniformity testing had consistent capsule-to-capsule API. Dissolution testing showed similar profiles between branded tacrolimus and Mylan, but notable differences with Dr. Reddy\'s and Intas. The approximate maximal inhibitory concentration (IC50) was highest in branded tacrolimus (29 minutes), followed by Mylan (26 minutes), Dr. Reddy\'s (19 minutes), and Intas (14 minutes) (Student-Newman-Keuls Multiple Comparisons Test; overall ANOVA: p = 0.0199, F = 6.469). This study suggests that the bioavailability of certain generic tacrolimus formulations peak significantly earlier than branded tacrolimus. Further study is needed to determine whether these differences are clinically relevant.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:569-572
Il'Giovine ZJ, Williams JB, Mason RP, Sherratt SCR, ... Mehra MR, Starling RC
J Heart Lung Transplant: 29 Jun 2021; 40:569-572 | PMID: 33903017
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Incidence and impact of primary graft dysfunction in adult heart transplant recipients: A systematic review and meta-analysis.

Buchan TA, Moayedi Y, Truby LK, Guyatt G, ... Alba AC, Foroutan F
Purpose
Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate risk factors for PGD, we systematically reviewed studies using the ISHLT 2014 Consensus Report definition and reporting the incidence of PGD in adult HTx recipients.
Methods
We conducted a systematic search in January 2020 including studies reporting the incidence of PGD in adult HTx recipients. We used a random effects model to pool the incidence of PGD among HTx recipients and, for each PGD severity, the mortality rate among those who developed PGD. For prognostic factors evaluated in ≥2 studies, we used random effects meta-analyses to pool the adjusted odds ratios for development of PGD. The GRADE framework informed our certainty in the evidence.
Results
Of 148 publications identified, 36 observational studies proved eligible. With moderate certainty, we observed pooled incidences of 3.5%, 6.6%, 7.7%, and 1.6% and 1-year mortality rates of 15%, 21%, 41%, and 35% for mild, moderate, severe and isolated right ventricular-PGD, respectively. Donor factors (female sex, and undersized), recipient factors (creatinine, and pre-HTx use of amiodarone, and temporary or durable mechanical support), and prolonged ischemic time proved associated with PGD post-HTx.
Conclusion
Our review suggests that the incidence of PGD may be low but its risk of mortality high, increasing with PGD severity. Prognostic factors, including undersized donor, recipient use of amiodarone pre-HTx and recipient creatinine may guide future studies in exploring donor and/or recipient selection and risk mitigation strategies.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:642-651
Buchan TA, Moayedi Y, Truby LK, Guyatt G, ... Alba AC, Foroutan F
J Heart Lung Transplant: 29 Jun 2021; 40:642-651 | PMID: 33947602
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Innate allorecognition in transplantation.

Abou-Daya KI, Oberbarnscheidt MH
Successful allogeneic transplantation has been made possible by suppressing activation of the adaptive immune system. Current immunosuppressive therapy prevents rejection by targeting T and B cells. Despite this effective treatment, it is the innate immune system, which includes dendritic cells, monocytes, natural killer cells, that is responsible for the initiation of the adaptive immune response. Recent work has described that the innate immune system is capable of recognizing allogeneic nonself and some of the mechanisms of innate allorecognition have been uncovered. Better understanding of the role of the innate immune system in initiation and maintenance of the allo-immune response has potential to lead to better treatment strategies for transplant patients, prolonging allograft survival. Here, we review advances in our understanding of innate allorecognition in transplantation.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:557-561
Abou-Daya KI, Oberbarnscheidt MH
J Heart Lung Transplant: 29 Jun 2021; 40:557-561 | PMID: 33958265
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Is pulmonary vascular resistance index better than pulmonary vascular resistance in predicting outcomes in pulmonary arterial hypertension?

Khirfan G, Li M, Wang X, Dweik RA, Heresi GA, Tonelli AR
Background
In contrast to pulmonary vascular resistance (PVR), PVR index (PVRI) accounts for variations in body habitus. We tested the association of PVRI compared to PVR with clinical outcomes in lean and obese (BMI ≥30 kg/m2) patients with pulmonary arterial hypertension (PAH).
Methods
This retrospective study included adult patients with PAH who underwent right heart catheterization at Cleveland Clinic between February 1992 and November 2019.
Results
We included 644 patients (mean age, 53 ± 16 years, and 74 % females). PAH was idiopathic or heritable in 44% of patients. Cardiac output increased (p <0.0001), while PVR decreased (p <0.0001) with increasing body weight. Both PVR and PVRI were associated with markers of disease severity, with more pronounced association for PVRI. Both PVR and PVRI were risk factors for first PAH hospitalization, mortality and mortality or lung transplant in the whole cohort and the group of patients with BMI < 30 kg/m2. However, PVRI (HR (95% CI): 1.06 (1.02 -1.11)), but not PVR (HR (95% CI): 1.03 (0.99-1.07)), was a risk factor for first PAH hospitalization in obese patients. In the obese group, neither PVR nor PVRI were risk factors for mortality.
Conclusions
PVRI appears to have a stronger association than PVR with disease severity markers in PAH; however, both PVR and PVRI were similarly associated with hospitalizations and survival in the overall cohort. We found no strong evidence to recommend a change from PVR to PVRI in the definition of PAH.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:614-622
Khirfan G, Li M, Wang X, Dweik RA, Heresi GA, Tonelli AR
J Heart Lung Transplant: 29 Jun 2021; 40:614-622 | PMID: 33962868
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term adult congenital heart disease survival after heart transplantation: A restricted mean survival time analysis.

Dolgner SJ, Nguyen VP, Krieger EV, Stempien-Otero A, Dardas TF
Background
Adult Congenital Heart Disease (ACHD) heart transplant recipients may have lower post-transplant survival resulting from higher peri-operative mortality than non-ACHD patients. However, the late risk of mortality appears lower in ACHD recipients. This study seeks to establish whether long-term heart transplant survival is reduced among ACHD recipients relative to non-ACHD recipients.
Methods
Adult patients who received a heart transplant between January, 2000 and December, 2019 in the United Network for Organ Sharing database were stratified by the presence of ACHD. Propensity-matched cohorts (1:4) were created to adjust for differences between groups. Graft survival at time points from 1 to 18 years was compared between groups using restricted mean survival time (RMST) analysis.
Results
The matched cohort included 1,139 ACHD and 4,293 non-ACHD patients. Median age was 35 years and 61% were male. Average survival time at 1 year was 0.85 years for ACHD patients and 0.93 years for non-ACHD patients (average difference: -0.08 years, 95% Confidence Interval [CI] -0.10 to -0.06, p < 0.001), reflecting higher immediate post-transplant mortality. Average survival time at 18 years was not clinically or statistically different: 11.14 years for ACHD patients and 11.40 years for non-ACHD patients (average difference: -0.26 years, 95% CI: -0.85 to + 0.32 years, p = 0.38).
Conclusions
Despite increased medium-term mortality among ACHD patients after heart transplant, differences in long-term survival are minimal. Allocation of hearts to ACHD patients results in acceptable utility of donor hearts.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:698-706
Dolgner SJ, Nguyen VP, Krieger EV, Stempien-Otero A, Dardas TF
J Heart Lung Transplant: 29 Jun 2021; 40:698-706 | PMID: 33965332
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pleural space management after lung transplant: Early and late outcomes of pleural decortication.

Rappaport JM, Siddiqui HU, Tang A, Thuita LW, ... Blackstone EH, Ahmad U
Background
Pleural complications after lung transplant may restrict allograft expansion, requiring decortication. However, its extent, indications, risk factors, and effect on allograft function and survival are unclear.
Methods
From January 2006 to January 2017, 1,039 patients underwent primary lung transplant and 468 had pleural complications, 77 (16%) of whom underwent 84 surgical decortications for pleural space management. Multivariable time-related analysis was performed to identify risk factors for decortication. Mixed-effect longitudinal modeling was used to assess allograft function before and after decortication.
Results
Cumulative number of decortications per 100 transplants was 1.8, 7.8, and 8.8 at 1 month, 1 year, and 3 years after transplant, respectively. Indications for the 84 decortications were complex effusion in 47 (56%), fibrothorax in 17 (20%), empyema in 11 (13%), and hemothorax in 9 (11%). Thoracoscopic operations were performed in 52 (62%) and full lung re-expansion was achieved in 76 (90%). Complications occurred after 30 (36%) decortications, with 15 pulmonary complications (18%), including 2 patients requiring extracorporeal support due to worsening function. Ten reinterventions occurred via thoracentesis (2), tube thoracostomy (1), and reoperation (7). In-hospital and 30-day mortality was 5.2% (n = 4/77). Forced expiratory volume in 1 second increased from 50% to 60% within the first year after decortication, followed by a slow decline to 55% at 5 years. Postdecortication survival was 87%, 68%, and 48% at 1, 3, and 5 years, respectively.
Conclusions
Despite high risk of reoperative surgery, decortication after lung transplant allows salvage of pleural space and graft function with a reasonable morbidity profile.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:623-630
Rappaport JM, Siddiqui HU, Tang A, Thuita LW, ... Blackstone EH, Ahmad U
J Heart Lung Transplant: 29 Jun 2021; 40:623-630 | PMID: 33994081
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Innate immunity in lung transplantation.

Shepherd HM, Gauthier JM, Li W, Krupnick AS, Gelman AE, Kreisel D
Innate immune pathways early after pulmonary transplantation have been shown to cause primary graft dysfunction (PGD) and also predispose to late graft failure. Recent studies in animal models have elucidated critical mechanisms governing such innate immune responses. Here, we discuss pathways of inflammatory cell death, triggers for sterile and infectious inflammation, and signaling cascades that mediate lung injury early after transplantation. These studies highlight potential avenues for lung-specific therapies early following lung transplantation to dampen innate immune responses and improve outcomes.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:562-568
Shepherd HM, Gauthier JM, Li W, Krupnick AS, Gelman AE, Kreisel D
J Heart Lung Transplant: 29 Jun 2021; 40:562-568 | PMID: 34020867
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cystic fibrosis foundation consensus statements for the care of cystic fibrosis lung transplant recipients.

Shah P, Lowery E, Chaparro C, Visner G, ... Pilewski JM, Hachem RR
Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:539-556
Shah P, Lowery E, Chaparro C, Visner G, ... Pilewski JM, Hachem RR
J Heart Lung Transplant: 29 Jun 2021; 40:539-556 | PMID: 34103223
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation.

Wang B, Zhou Q, Li A, Li S, ... Liu K, Zheng X
Background
While heart transplantation is used as a standard treatment for heart failure, transplant rejection continues to pose a challenge. Recent evidence has shown that circular RNA (circRNA) is a new type of gene regulator in cell development. Our aim was to demonstrate that treatment with tolerogenic dendritic cells (Tol-DCs) generated by circular RNA FSCN1 (circFSCN1) silencing could prevent alloimmune rejection and prolong heart graft survival in heart transplantation.
Methods
Bone marrow-derived DCs were transfected with circFSCN1 siRNA in vitro. The circFSCN1 level was measured by qRT-PCR. DC maturation was determined by flow cytometry. Mixed lymphocyte reactions (MLRs) were conducted to assess the function of DCs to activate T cells and to generate regulatory T cells (Tregs). In situ RNA hybridization and fluorescent microscopy were performed to detect the distribution of circFSCN1 in DCs. A heterotopic allogeneic murine heart transplantation was conducted where recipients were pre-treated with donor derived circFSCN1-silenced Tol-DCs. Heartbeat was monitored to assess immune rejection.
Results
Exonic circFSCN1 was highly expressed in the cytoplasm of mature DCs. Knockdown of circFSCN1 using siRNA arrested DCs at an immature state, impaired DC\'s ability to activate T cells and enhanced Treg generation. Treatment with circFSCN1-silenced Tol-DCs prevented alloimmune rejection, prolonged allograft survival, reduced fibrosis, and induced Tregs in vivo.
Conclusions
Knockdown of circFSCN1 induces Tol-DCs and treatment with these Tol-DCs prevents alloimmune rejection and prolongs allograft survival. This is a promising therapeutic target to combat transplant rejection in heart transplantation and increases our understanding of circRNA in the immune system.

Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:584-594
Wang B, Zhou Q, Li A, Li S, ... Liu K, Zheng X
J Heart Lung Transplant: 29 Jun 2021; 40:584-594 | PMID: 34052126
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Comparison of de novo donor-specific antibodies between living and cadaveric lung transplantation.

Gochi F, Chen-Yoshikawa TF, Kayawake H, Ohsumi A, ... Hishida R, Date H
Background
Despite growing interest in donor-specific antibodies (DSAs) and antibody-mediated rejection (AMR) in lung transplantation (LTx), no study evaluating the outcomes in recipients with de novo DSAs (dnDSAs) in living-donor lobar LTx (LDLLT) exists. We compared various characteristics of DSAs in LDLLT with those in cadaveric LTx (CLT) based on prospectively collected data.
Methods
Between October 2009 and September 2019, 211 recipients underwent LTx (128 CLTs and 83 LDLLTs). We reviewed 108 CLTs and 74 LDLLTs to determine the characteristics and clinical impact of dnDSAs. Eighteen data-deficient cases, 7 cases with preformed DSAs, and 4 re-transplants were excluded.
Results
There were significant differences between CLT and LDLLT patients in age, primary disease, ischemic time, and number of human leukocyte antigen mismatches per donor. The dnDSA incidence in LDLLT (6.8%) was significantly lower than that in CLT (19.4%, p = 0.02). The dnDSAs appeared later in LDLLT (mean 1,256 days) than in CLT (mean 196 days, p = 0.003). According to Cox models analyzed using dnDSA as a time-dependent covariate, dnDSA positivity was significantly associated with a poor overall survival (OS; hazard ratio [HR] 3.46, 95% confidence interval [CI] 1.59-7.57, p = 0.002) and poor CLAD-free survival in case of CLT (HR: 2.23, 95% CI: 1.08-4.63, p = 0.003). However, no such significant associations were noted in case of LDLLT.
Conclusions
The dnDSA occurrence was significantly lower and later in LDLLT than in CLT. Furthermore, dnDSA-positivity was significantly associated with worse OS and CLAD-free survival after CLT but not after LDLLT.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; 40:607-613
Gochi F, Chen-Yoshikawa TF, Kayawake H, Ohsumi A, ... Hishida R, Date H
J Heart Lung Transplant: 29 Jun 2021; 40:607-613 | PMID: 34078558
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A simplified strategy for donor-recipient size-matching in lung transplant for interstitial lung disease.

Riddell P, Ma J, Dunne B, Binnie M, ... Singer LG, Keshavjee S
Background
Donor-recipient size-matching has been repeatedly reported to improve outcomes following lung transplantation (LTx). However, there is significant variability in practice and the optimal strategy for size-matching is yet to be defined. For recipients with ILD, size-matching decisions are complicated by concerns regarding the potential impact of pre-LTx pulmonary restriction. We evaluate whether a specific donor-to-recipient size-matching strategy, based on predicted total lung capacity, benefits this patient group.
Methods
This retrospective, single-centre, cohort study describes the post-LTx outcomes of adults who underwent LTx for ILD between 1983 and 2020. Only patients with restrictive physiology, based on pre-LTx pulmonary function testing were included. Post-LTx outcomes were compared based on donor-recipient predicted TLC (D-R pTLC) ratio. A D-R pTLC ratio of ≥0.8 or <1.2 for DLTx, and a D-R pTLC ratio of ≥0.8 or <1.0 for SLTx were classified as \'size-matched\'.
Results
Five-hundred and fifty LTx recipients met inclusion criteria. Of these, 404 underwent DLTx and 146 underwent SLTx. Size-matching was achieved in 78% of DLTx and 47% of SLTx. Overall survival (p = 0.007) and CLAD-free survival (p < 0.001) was significantly improved following a size-matched DLTx, compared to those with D-R pTLC ratios <0.8 or ≥1.2. Size-matching based on a D-R pTLC ratio 0.8≥ <1.0 for SLTX did not significantly improve survival.
Conclusions
D-R pTLC size-matching, based on a ratio of 0.8≥ <1.2 improved post-DLTx outcomes for patients with restrictive lung disease. This is simple to do, and if applied clinically, could improve overall outcomes in lung transplantation.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Jun 2021; epub ahead of print
Riddell P, Ma J, Dunne B, Binnie M, ... Singer LG, Keshavjee S
J Heart Lung Transplant: 29 Jun 2021; epub ahead of print | PMID: 34301464
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles.

Akhmerov A, Rogers R, de Couto G, Valle J, ... Liu W, Marbán E
Background
Extracellular vesicles (EVs) from heart stromal/progenitor cells modulate innate immunity, with salutary effects in a variety of cardiac disease models. Little is known, however, about the effects of these EVs on adaptive immunity.
Methods
Ex vivo differentiation of naïve CD4+ T cells was conducted to assess the effect of EVs on cytokine production and proliferation of Th1, Th2, Th17, and regulatory T (Treg) cells. These effects were further tested in vivo using the experimental autoimmune myocarditis (EAM) model.
Results
Using differentiated CD4+ T cells, we show that EVs secreted by human-derived heart stromal/progenitor cells selectively influence the phenotype, activity, and proliferation of regulatory T (Treg) cells. Exposure of Treg cells to EVs results in faster proliferation, augmented production of IL-10, and polarization toward an intermediate FOXP3+RORγt+ phenotype. In experimental autoimmune myocarditis, EVs attenuate cardiac inflammation and functional decline, in association with increased numbers of splenic IL10+-Treg cells.
Conclusions
T cell modulation by EVs represents a novel therapeutic approach to inflammation, harnessing endogenous immunosuppressive mechanisms that may be applied in solid organ transplantation, graft-versus-host disease, and autoimmune disorders.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 23 Jun 2021; epub ahead of print
Akhmerov A, Rogers R, de Couto G, Valle J, ... Liu W, Marbán E
J Heart Lung Transplant: 23 Jun 2021; epub ahead of print | PMID: 34281778
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Development and validation of specific post-transplant risk scores according to the circulatory support status at transplant: A UNOS cohort analysis.

Coutance G, Bonnet G, Kransdorf EP, Loupy A, ... Kobashigawa JA, Patel JK
Background
The clinical use of post-transplant risk scores is limited by their poor statistical performance. We hypothesized that developing specific prognostic models for each type of circulatory support at transplant may improve risk stratification.
Methods
We analyzed the UNOS database including contemporary, first, non-combined heart transplantations (2013-2018). The endpoint was death or retransplantation during the first year post-transplant. Three different circulatory support statuses at transplant were considered: no support, durable mechanical support and temporary support (inotropes, temporary mechanical support). We generated 1,000 bootstrap samples that we randomly split into derivation and test sets. In each sample, we derived an overall model and 3 specific models (1 for each type of circulatory support) using Cox regressions, and compared, in the test set, their statistical performance for each type of circulatory support.
Results
A total of 13,729 patients were included; 1,220 patients (8.9%) met the composite endpoint. Circulatory support status at transplant was associated with important differences in baseline characteristics and distinct prognosis (p = 0.01), interacted significantly with important predictive variables included in the overall model, and had a major impact on post-transplant predictive models (type of variables included and their corresponding hazard ratios). However, specific models suffered from poor discriminative performance and significantly improved risk stratification (discrimination, reclassification indices, calibration) compared to overall models in a very limited proportion of bootstrap samples (<15%). These results were consistent across several sensitivity analyzes.
Conclusion
Circulatory support status at transplant reflected different disease states that influenced predictive models. However, developing specific models for each circulatory support status did not significantly improve risk stratification.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 23 Jun 2021; epub ahead of print
Coutance G, Bonnet G, Kransdorf EP, Loupy A, ... Kobashigawa JA, Patel JK
J Heart Lung Transplant: 23 Jun 2021; epub ahead of print | PMID: 34274182
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

IRF4 ablation in B cells abrogates allogeneic B cell responses and prevents chronic transplant rejection.

Wang G, Zou D, Wang Y, Gonzalez NM, ... Chen W, Gaber AO
Backgound
B cells contribute to chronic transplant rejection by producing donor-specific antibodies and promoting T cell response, but how these processes are regulated at the transcriptional level remains unclear. Herein, we investigate the role of transcription factor interferon regulatory factor 4 (IRF4) in controlling B cell response during chronic transplant rejection.
Methods
We generated the Irf4gfp reporter mice to determine IRF4 expression in B cell lineage. We then used mice with B cell-specific IRF4 deletion to define the role of IRF4 in B cell response after NP-KLH immunization or allogeneic heart transplantation. In particular, graft survival and histology, as well as B and T cell responses, were evaluated after transplantation.
Results
IRF4 is dynamically expressed at different stages of B cell development and is absent in germinal center (GC) B cells. However, IRF4 ablation in the B cell lineage primarily eliminates GC B cells in both naïve and NP-KLH immunized mice. In the transplantation setting, IRF4 functions intrinsically in B cells and governs allogeneic B cell responses at multiple levels, including GC B cell generation, plasma cell differentiation, donor-specific antibody production, and support of T cell response. B cell-specific IRF4 deletion combined with transient CTLA4-Ig treatment abrogates acute and chronic cardiac allograft rejection in naïve recipient mice but not in donor skin-sensitized recipients.
Conclusions
B cells require IRF4 to mediate chronic transplant rejection. IRF4 ablation in B cells abrogates allogeneic B cell responses and may also inhibit the ability of B cells to prime allogenic T cells. Targeting IRF4 in B cells represents a potential therapeutic strategy for eliminating chronic transplant rejection.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 22 Jun 2021; epub ahead of print
Wang G, Zou D, Wang Y, Gonzalez NM, ... Chen W, Gaber AO
J Heart Lung Transplant: 22 Jun 2021; epub ahead of print | PMID: 34253454
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lung transplantation using allografts with more than 8 hours of ischemic time: A single-institution experience.

Halpern SE, Au S, Kesseli SJ, Krischak MK, ... Klapper JA, Hartwig MG
Background
Six hours was historically regarded as the limit of acceptable ischemic time for lung allografts. However, broader sharing of donor lungs often necessitates use of allografts with ischemic time >6 hours. We characterized the association between ischemic time ≥8 hours and outcomes after lung transplantation using a contemporary cohort from a high-volume institution.
Methods
Patients who underwent primary isolated bilateral lung transplantation between 1/2016 and 5/2020 were included. Patients bridged to transplant with extracorporeal membrane oxygenation or mechanical ventilation, and ex-vivo perfusion cases were excluded. Recipients were stratified by total allograft ischemic time <8 hours (standard) vs ≥8 hours (long). Perioperative outcomes and post-transplant survival were compared between groups.
Results
Of 358 patients, 95 (26.5%) received long ischemic time (≥8 hours) lungs. Long ischemic time recipients were more likely to be male and have donation after circulatory death donors than standard ischemic time recipients. On unadjusted analysis, long and standard ischemic time recipients had similar survival, and similar rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation post-transplant, acute rejection within 30 days, reintubation, and post-transplant length of stay. After adjustment, long and standard ischemic time recipients had comparable risks of mortality or graft failure.
Conclusions
In a modern cohort, use of lung allografts with \"long\" ischemic time ≥8 hours were associated with acceptable perioperative outcomes and post-transplant survival. Further investigation is required to better understand how broader use impacts post-lung transplant outcomes and the implications for smarter sharing under an evolving national allocation policy.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 22 Jun 2021; epub ahead of print
Halpern SE, Au S, Kesseli SJ, Krischak MK, ... Klapper JA, Hartwig MG
J Heart Lung Transplant: 22 Jun 2021; epub ahead of print | PMID: 34281776
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

COVID-19 diagnosis and testing in pediatric heart transplant recipients.

Bock MJ, Kuhn MA, Chinnock RE
Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of infection, COVID-19 is well tolerated in this population (5% admission from home; 0% mortality). A suppressed immune system does not significantly inhibit an antibody response in pediatric heart transplant recipients (>70% antibody seroconversion) and appears to persist, similar to those without transplantation (>90 days). Routine testing for COVID-19 via PCR and antibody testing enhances the ability to detect COVID-19 infection in asymptomatic patients and may help reduce unintended transmission to more susceptible individuals.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 16 Jun 2021; epub ahead of print
Bock MJ, Kuhn MA, Chinnock RE
J Heart Lung Transplant: 16 Jun 2021; epub ahead of print | PMID: 34253455
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of thoracotomy approach on right ventricular failure and length of stay in left ventricular assist device implants: an intermacs registry analysis.

Lampert BC, Teuteberg JJ, Cowger J, Mokadam NA, ... Kirklin JK, Whitson BA
Introduction
Traditionally, implantation of Left Ventricular Assist Devices (LVADs) is performed via median sternotomy. Recently, less invasive thoracotomy approaches are growing in popularity as they involve less surgical trauma, potentially less bleeding, and may preserve right ventricular function. We hypothesized implantation of LVADs via thoracotomy has less perioperative right ventricular failure (RVF) and shorter postoperative length of stay (LOS).
Methods
Continuous flow LVAD implants from Intermacs between February 6, 2014 - December 31, 2018 were identified. Patients implanted via thoracotomy were propensity matched in a 1:1 ratio with patients implanted via sternotomy. Outcomes were compared between sternotomy and thoracotomy approach and by device type (axial, centrifugal-flow with hybrid levitation (CF-HL), centrifugal-flow with full magnetic levitation devices (CF-FML)). The primary outcome was time to first moderate or severe RVF. Secondary outcomes included survival and LOS.
Results
Overall 978 thoracotomy patients were matched with 978 sternotomy patients. Over the study period, 242 thoracotomy patients and 219 sternotomy patients developed RVF with no significant difference in time to first moderate to severe RVF by surgical approach overall (p = 0.27) or within CF-HL (p = 0.36) or CF-FML devices (p = 0.25). Survival did not differ by implant technique (150 deaths in thoracotomy group, 154 deaths in sternotomy group; p = 0.58). However, sternotomy approach was associated with a significantly shorter LOS (17 Vs 18 days, p = 0.009).
Conclusion
As compared to sternotomy, implantation of continuous flow LVADs via thoracotomy approach does not reduce moderate to severe RVF or improve survival but does reduce post-operative LOS. Device type did not influence outcomes and most centers did a small volume of thoracotomy implants.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 Jun 2021; epub ahead of print
Lampert BC, Teuteberg JJ, Cowger J, Mokadam NA, ... Kirklin JK, Whitson BA
J Heart Lung Transplant: 11 Jun 2021; epub ahead of print | PMID: 34229917
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Gender and racial disparities in lung transplantation in the United States.

Riley LE, Lascano J
Background
Lung transplant (LT) allocation utilizes a scoring system to prioritize patients, although data evaluating the access by gender and race remains limited. The study objective was to determine whether gender and racial disparities exist in patients listed for LT.
Methods
This was a retrospective analysis using the Organ Procurement and Transplant Network database of patients listed for a LT from 1984 until 2019. Nominal multivariate logistic regression analysis was performed to evaluate LT allocation by gender, race, and primary lung disease. Kaplan-Meier curves were constructed to compare rates of mortality over time.
Results
Sixty thousand eight hundred and forty-seven patients were listed between February 1984 and September 2019. Males comprised the majority of listed and transplanted patients at 51.7% and 55.8% respectively. In the LAS era, the median waiting list time for transplanted males was 43 days (interquartile range [IQR] 13-126), and females waited a median of 80 days (IQR 24-233) (p < .001). Persons of White race accounted for 82.6% and 84.3% of listed and transplanted patients respectively. Logistic regression analysis found that in the LAS era, males had an increased odds for LT allocation (OR 1.19, CI 1.12-1.27, p < .001) compared to females, and persons of White race (OR 1.23, CI 1.16-1.32, p < .001) compared to all other races combined.
Conclusions
The majority of listed and transplanted patients in the United States were males and persons of White race. Also, being a male or person of White race had an outcome favoring lung transplant allocation compared to an appropriately matched person of another gender or race.

Published by Elsevier Inc.

J Heart Lung Transplant: 11 Jun 2021; epub ahead of print
Riley LE, Lascano J
J Heart Lung Transplant: 11 Jun 2021; epub ahead of print | PMID: 34246564
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Variants in mycophenolate and CMV antiviral drug pharmacokinetic and pharmacodynamic genes and leukopenia in heart transplant recipients.

Oreschak K, Saba LM, Rafaels N, Ambardekar AV, ... Lindenfeld J, Aquilante CL
Background
The objective was to assess the relationship between single nucleotide polymorphisms in mycophenolate and cytomegalovirus antiviral drug pharmacokinetic and pharmacodynamic genes and drug-induced leukopenia in adult heart transplant recipients.
Methods
This retrospective analysis included n = 148 patients receiving mycophenolate and a cytomegalovirus antiviral drug. In total, 81 single nucleotide polymorphisms in 21 pharmacokinetic and 23 pharmacodynamic genes were selected for investigation. The primary and secondary outcomes were mycophenolate and/or cytomegalovirus antiviral drug-induced leukopenia, defined as a white blood cell count <3.0 × 109/L, in the first six and 12 months post-heart transplant, respectively.
Results
Mycophenolate and/or cytomegalovirus antiviral drug-induced leukopenia occurred in 20.3% of patients. HNF1A rs1169288 A>C (p.I27L) was associated with drug-induced leukopenia (unadjusted p = 0.002; false discovery rate <20%) in the first six months post-transplant. After adjusting for covariates, HNF1A rs1169288 variant C allele carriers had significantly higher odds of leukopenia compared to A/A homozygotes (odds ratio 6.19; 95% CI 1.97-19.43; p = 0.002). Single nucleotide polymorphisms in HNF1A, SLC13A1, and MBOAT1 were suggestively associated (p < 0.05) with the secondary outcome but were not significant after adjusting for multiple comparisons.
Conclusion
Our data suggest genetic variation may play a role in the development of leukopenia in patients receiving mycophenolate and cytomegalovirus antiviral drugs after heart transplantation. Following replication, pharmacogenetic markers, such as HNF1A rs1169288, could help identify patients at higher risk of drug-induced leukopenia, allowing for more personalized immunosuppressant therapy and cytomegalovirus prophylaxis following heart transplantation.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 Jun 2021; epub ahead of print
Oreschak K, Saba LM, Rafaels N, Ambardekar AV, ... Lindenfeld J, Aquilante CL
J Heart Lung Transplant: 11 Jun 2021; epub ahead of print | PMID: 34253456
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Study results suggest less invasive HeartMate 3 implantation is a safe and effective approach for obese patients.

Bjelic M, Ayers B, Paic F, Bernstein W, ... Prasad S, Gosev I
Background
Historically, obesity was considered a relative contraindication to left ventricular assist device (LVAD) implantation with less invasive surgery (LIS). The present study aimed to compare the outcomes of obese patients who underwent LVAD implantation through LIS with those who received full sternotomy (FS) implantation.
Methods
We retrospectively reviewed all patients implanted with HeartMate 3 LVAD in our institution between September 2015 and June 2020. Obese patients (BMI ≥ 30 kg/m2) were included and dichotomized based on surgical approach into the FS or LIS cohort.
Results
Of 231 implanted patients, 107 (46%) were obese and included in the study. FS was performed in 26 (24%) patients and LIS approach in 81 (76%) patients. Preoperative patient characteristics were similar between the cohorts. Postoperatively, patients in LIS cohort had less bleeding (p = 0.029), fewer transfusions (p = 0.042), shorter duration of inotropic support (p = 0.049), and decreased incidence of severe RV failure (11.1% vs 30.8%, p = 0.028). Survival to discharge for the obese population was 87.5% overall and did not differ based on an approach (91.4% LIS vs 76.9% FS, p = 0.079). More LIS patients were discharged home (60.0% vs 82.4%, p = 0.041) rather than to rehabilitation center.
Conclusion
Our results showed that the LIS approach in obese patients is associated with fewer postoperative complications and a trend towards better short-term survival. These results suggest that less invasive LVAD implantation is a safe and effective approach for obese patients. Future prospective randomized trials are required to substantiate these results.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 10 Jun 2021; epub ahead of print
Bjelic M, Ayers B, Paic F, Bernstein W, ... Prasad S, Gosev I
J Heart Lung Transplant: 10 Jun 2021; epub ahead of print | PMID: 34229916
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

Edelson JB, Huang Y, Griffis H, Huang J, ... O\'Connor MJ, Rossano JW
Background
Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort.
Methods
This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke.
Results
26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status.
Conclusion
Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 10 Jun 2021; epub ahead of print
Edelson JB, Huang Y, Griffis H, Huang J, ... O'Connor MJ, Rossano JW
J Heart Lung Transplant: 10 Jun 2021; epub ahead of print | PMID: 34253457
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.

Benck L, Kransdorf EP, Emerson DA, Rushakoff J, ... Kobashigawa JA, Patel JK
Background
Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). The International Society for Heart and Lung Transplantation (ISHLT) subdivides PGD into 3 grades of increasing severity. Most studies have assessed risk factors for PGD without distinguishing between PGD severity grade. We sought to identify recipient, donor and surgical risk factors specifically associated with mild/moderate or severe PGD.
Methods
We identified 734 heart transplant recipients at our institution transplanted between January 1, 2012 and December 31, 2018. PGD was defined according to modified ISHLT criteria. Recipient, donor and surgical variables were analyzed by multinomial logistic regression with mild/moderate or severe PGD as the response. Variables significant in single variable modeling were subject to multivariable analysis via penalized logistic regression.
Results
PGD occurred in 24% of the cohort (n = 178) of whom 6% (n = 44) had severe PGD. One-year survival was reduced in recipients with severe PGD but not in those with mild or moderate PGD. Multivariable analysis identified 3 recipient factors: prior cardiac surgery, recipient treatment with ACEI/ARB/ARNI plus MRA, recipient treatment with amiodarone plus beta-blocker, and 3 surgical factors: longer ischemic time, more red blood cell transfusions, and more platelet transfusions, that were associated with severe PGD. We developed a clinical risk score, ABCE, which provided acceptable discrimination and calibration for severe PGD.
Conclusions
Risk factors for mild/moderate PGD were largely distinct from those for severe PGD, suggesting a differing pathophysiology involving several biological pathways. Further research into mechanisms underlying the development of PGD is urgently needed.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 09 Jun 2021; epub ahead of print
Benck L, Kransdorf EP, Emerson DA, Rushakoff J, ... Kobashigawa JA, Patel JK
J Heart Lung Transplant: 09 Jun 2021; epub ahead of print | PMID: 34272125
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation.

Hasenauer A, Bédat B, Parapanov R, Lugrin J, ... Krueger T, Liaudet L
Background
Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP).
Methods
Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1β, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined.
Results
Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs.
Conclusions
The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 31 May 2021; epub ahead of print
Hasenauer A, Bédat B, Parapanov R, Lugrin J, ... Krueger T, Liaudet L
J Heart Lung Transplant: 31 May 2021; epub ahead of print | PMID: 34193360
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical utility of donor-derived cell-free DNA testing in cardiac transplantation.

Khush KK
Surveillance of allograft health after transplantation has traditionally relied on biopsy procedures that enable pathologic assessment for acute rejection. Noninvasive methods to assess for graft injury have been developed and tested over the past decade, and now offer a convenient way to reduce reliance on invasive testing and improve patient satisfaction. Emerging evidence suggests that detection of allograft injury via donor-derived cell-free DNA (dd-cfDNA) may, in fact, have better sensitivity compared to traditional biopsy-based strategies. This state-of-the-art review describes the development, testing, and current use of dd-cfDNA assays for acute rejection monitoring after heart transplantation, and discusses innovative ways that such assays can be used for personalized patient management.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:397-404
Khush KK
J Heart Lung Transplant: 30 May 2021; 40:397-404 | PMID: 33610430
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Once daily tacrolimus conversion in lung transplantation: A prospective study on safety and medication adherence.

Godinas L, Dobbels F, Hulst L, Verbeeck I, ... Verleden GM, Vos R
Background
Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking.
Methods
In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)).
Results
We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion.
Conclusions
In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:467-477
Godinas L, Dobbels F, Hulst L, Verbeeck I, ... Verleden GM, Vos R
J Heart Lung Transplant: 30 May 2021; 40:467-477 | PMID: 33840608
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exercise right ventricular ejection fraction predicts right ventricular contractile reserve.

Ireland CG, Damico RL, Kolb TM, Mathai SC, ... Tedford RJ, Hsu S
Background
Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes.
Methods
We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period.
Results
RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R2 = 0.76, p< 0.001). RV Ees and dilation changes each predicted resting RV-PA dysfunction. RV ejection fraction during exercise, which captured exertional changes in both RV Ees and RV dilation, proved to be a robust surrogate for RV contractile reserve. Reduced exercise RV ejection fraction best predicted occult RV dysfunction among a variety of resting and exercise RV measures, and was also associated with clinical worsening.
Conclusions
RV ejection fraction during exercise, as an index of RV contractile reserve, allows for excellent identification of occult RV dysfunction, more so than resting measures of RV function, and may predict clinical outcomes as well.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:504-512
Ireland CG, Damico RL, Kolb TM, Mathai SC, ... Tedford RJ, Hsu S
J Heart Lung Transplant: 30 May 2021; 40:504-512 | PMID: 33752973
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Right ventricular adaptation to pressure-overload: Differences between chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension.

Braams NJ, van Leeuwen JW, Vonk Noordegraaf A, Nossent EJ, ... Meijboom LJ, de Man FS
Background
Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) are both associated with right ventricular (RV) failure and mortality. However, CTEPH patients are older, more often male and usually have more co-morbidities than iPAH patients, including a history of venous thromboembolism. Therefore, RV adaptation to pressure-overload in CTEPH may be different than in iPAH.
Methods
We included all treatment-naive CTEPH and iPAH patients diagnosed in the Amsterdam UMC between 2000 and 2019 if cardiac magnetic resonance imaging (CMR) and a right heart catheterization were performed at time of diagnosis. Load-dependent RV volumes and mass were assessed with CMR. Load-independent RV contractility, afterload and diastolic stiffness in relation to afterload were obtained using single beat pressure-volume loop analysis. Differences in RV characteristics between CTEPH and iPAH were analyzed using multiple linear regression with interaction testing after correcting for confounders.
Results
We included 235 patients in this study and performed pressure-volume loop analysis in 136 patients. In addition to being older and more often male, CTEPH patients had a lower pulmonary vascular resistance than iPAH patients at the time of diagnosis. After correcting for these confounders, CTEPH patients had a somewhat higher RV end-diastolic volume index (87 ± 27 ml vs 82 ± 25 ml; p < .01), and a lower RV relative wall thickness (0.6 ± 0,1 g/ml vs 0.7 ± 0,2 g/ml; p < .01). The correlation coefficient of RV diastolic stiffness to afterload was higher in CTEPH compared to iPAH (p < .05; independent of age and gender).
Conclusions
Despite differences in patient characteristics, disease etiology and physiology, RV functional parameters in CTEPH and iPAH are mostly similar. The right ventricle in CTEPH is marginally more dilated, stiffer and less hypertrophic than in iPAH.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:458-466
Braams NJ, van Leeuwen JW, Vonk Noordegraaf A, Nossent EJ, ... Meijboom LJ, de Man FS
J Heart Lung Transplant: 30 May 2021; 40:458-466 | PMID: 33745783
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence.

Sammour Y, Nassif M, Magwire M, Thomas M, ... O\'Keefe J, Kosiborod M
Type 2 diabetes mellitus (T2D) is a common comorbidity among patients who have undergone heart transplantation. Recently two classes of glucose-lowering medications (sodium-glucose cotransporter type-2 inhibitors [SGLT-2Is] and glucagon-like-peptide-1 receptor agonists [GLP-1RAs]), have been shown to significantly improve cardiovascular outcomes. There is a paucity of data regarding their use in immunosuppressed patients, with many studies specifically excluding this population. We retrospectively evaluated the safety and efficacy of GLP-1RAs and SGLT-2Is in patients who had undergone orthotopic heart transplant at a high-volume center. Among 21 patients, we found significant weight loss, reductions in insulin use, hemoglobin A1c, and low-density lipoprotein-cholesterol. Moreover, both SGLT-2Is and GLP-1RAs were well tolerated with no adverse events leading to discontinuation of either therapy. While larger studies of patients after solid organ transplant are needed, this small hypothesis-generating study demonstrates that SGLT-2Is and GLP-1RAs appear safe and effective therapies among patients with T2D after heart transplant.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 30 May 2021; 40:426-429
Sammour Y, Nassif M, Magwire M, Thomas M, ... O'Keefe J, Kosiborod M
J Heart Lung Transplant: 30 May 2021; 40:426-429 | PMID: 33745782
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: A post hoc subgroup analysis of the RISE-IIP study.

Nathan SD, Cottin V, Behr J, Hoeper MM, ... Nikkho S, Wells AU
Background
Riociguat in Patients with Symptomatic Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (RISE-IIP), a randomized, controlled, phase 2b trial of riociguat for pulmonary hypertension associated with idiopathic interstitial pneumonia, was terminated early due to increased mortality in riociguat-treated patients. Baseline characteristics of enrolled patients demonstrated a low diffusing capacity of the lung for carbon monoxide (DLCO) with preserved lung volumes at baseline, suggesting the presence of combined pulmonary fibrosis and emphysema (CPFE) in some patients. This post hoc analysis of RISE-IIP was undertaken to explore lung morphology, assessed by high-resolution computed tomography, and associated clinical outcomes.
Methods
Available baseline/pre-baseline high-resolution computed tomography scans were reviewed centrally by 2 radiologists. The extent of emphysema and fibrosis was retrospectively scored and combined to provide the total CPFE score.
Results
Data were available for 65/147 patients (44%), including 15/27 fatal cases (56%). Of these, 41/65 patients (63%) had CPFE. Mortality was higher in patients with CPFE (12/41; 29%) than those without (3/24; 13%). Fourteen patients with CPFE had emphysema > fibrosis (4 died). No relationship was observed between CPFE score, survival status, and treatment assignment. A low DLCO, short 6-min walking distance, and high forced vital capacity:DLCO ratio at baseline also appeared to be risk factors for mortality.
Conclusions
High parenchymal lung disease burden and the presence of more emphysema than fibrosis might have predisposed patients with pulmonary hypertension associated with idiopathic interstitial pneumonia to poor outcomes in RISE-IIP. Future studies of therapy for group 3 pulmonary hypertension should include centrally adjudicated imaging for morphologic phenotyping and disease burden evaluation during screening.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:494-503
Nathan SD, Cottin V, Behr J, Hoeper MM, ... Nikkho S, Wells AU
J Heart Lung Transplant: 30 May 2021; 40:494-503 | PMID: 33744088
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Resource utilization in children with paracorporeal continuous-flow ventricular assist devices.

Burstein DS, Griffis H, Zhang X, Cantor RS, ... Kirklin JK, Rossano JW
Background
Paracorporeal continuous-flow ventricular assist devices (PCF VAD) are increasingly used in pediatrics, yet PCF VAD resource utilization has not been reported to date.
Methods
Pediatric Interagency Registry for Mechanically Assisted Circulatory Support (PediMACS), a national registry of VADs in children, and Pediatric Health Information System (PHIS), an administrative database of children\'s hospitals, were merged to assess VAD implants from 19 centers between 2012 and 2016. Resource utilization, including hospital and intensive care unit length of stay (LOS), and costs are analyzed for PCF VAD, durable VAD (DVAD), and combined PCF-DVAD support.
Results
Of 177 children (20% PCF VAD, 14% PCF-DVAD, 66% DVAD), those with PCF VAD or PCF-DVAD are younger (median age 4 [IQR 0-10] years and 3 [IQR 0-9] years, respectively) and more often have congenital heart disease (44%; 28%, respectively) compared to DVAD (11 [IQR 3-17] years; 14% CHD); p < 0.01 for both. Median post-VAD LOS is prolonged ranging from 43 (IQR 15-82) days in PCF VAD to 72 (IQR 55-107) days in PCF-DVAD, with significant hospitalization costs (PCF VAD $450,000 [IQR $210,000-$780,000]; PCF-DVAD $770,000 [IQR $510,000-$1,000,000]). After adjusting for patient-level factors, greater post-VAD hospital costs are associated with LOS, ECMO pre-VAD, greater chronic complex conditions, and major adverse events (p < 0.05 for all). VAD strategy and underlying cardiac disease are not associated with LOS or overall costs, although PCF VAD is associated with higher daily-level costs driven by increased pharmacy, laboratory, imaging, and clinical services costs.
Conclusion
Pediatric PCF VAD resource utilization is staggeringly high with costs primarily driven by pre-implantation patient illness, hospital LOS, and clinical care costs.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:478-487
Burstein DS, Griffis H, Zhang X, Cantor RS, ... Kirklin JK, Rossano JW
J Heart Lung Transplant: 30 May 2021; 40:478-487 | PMID: 33744087
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Assessing hemodynamic response to submaximal exercise in pulmonary arterial hypertension patients using an implantable hemodynamic monitor.

Airhart S, Badie N, Doyle M, Correa-Jacque P, Daniels C, Benza R
Pulmonary arterial hypertension (PAH) is a chronic, progressive disease that is incurable, even with effective therapy. Long-term outcome in PAH is best preserved by targeting hemodynamic improvements to reduce risk of subsequent right ventricular (RV) failure. Methods that can assess RV adaptation to stress have important implications to better understand an individual\'s physiology and may play a pivotal role in guiding therapy in PAH. In this novel pilot study, we evaluate the feasibility of monitoring hemodynamic response to 6-minute walk distance in patients with PAH using the CardioMEMS HF System.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:430-434
Airhart S, Badie N, Doyle M, Correa-Jacque P, Daniels C, Benza R
J Heart Lung Transplant: 30 May 2021; 40:430-434 | PMID: 33752972
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Machine learning, artificial intelligence and mechanical circulatory support: A primer for clinicians.

Kanwar MK, Kilic A, Mehra MR
Artificial intelligence (AI) refers to the ability of machines to perform intelligent tasks, and machine learning (ML) is a subset of AI describing the ability of machines to learn independently and make accurate predictions. The application of AI combined with \"big data\" from the electronic health records, is poised to impact how we take care of patients. In recent years, an expanding body of literature has been published using ML in cardiovascular health care, including mechanical circulatory support (MCS). This primer article provides an overview for clinicians on relevant concepts of ML and AI, reviews predictive modeling concepts in ML and provides contextual reference to how AI is being adapted in the field of MCS. Lastly, it explains how these methods could be incorporated in the practices of medicine to improve patient outcomes.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:414-425
Kanwar MK, Kilic A, Mehra MR
J Heart Lung Transplant: 30 May 2021; 40:414-425 | PMID: 33775520
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction.

Banday MM, Kumar A, Vestal G, Sethi J, ... Seyfang A, Sharma NS
Background
Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT).
Methods
Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI.
Results
16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes. At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella. Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response.
Conclusions
CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia.

Published by Elsevier Inc.

J Heart Lung Transplant: 30 May 2021; 40:447-457
Banday MM, Kumar A, Vestal G, Sethi J, ... Seyfang A, Sharma NS
J Heart Lung Transplant: 30 May 2021; 40:447-457 | PMID: 33781665
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD).

Keller M, Bush E, Diamond JM, Shah P, ... Jang M, Agbor-Enoh S
Background
Primary graft dysfunction (PGD) is a risk factor for chronic lung allograft dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD.
Methods
This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3, and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not.
Results
On posttransplant day 3, %ddcfDNA was higher in PGD than in non-PGD patients (median [IQR]: 12.2% [8.2, 22.0] vs 8.5% [5.6, 13.2] p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p = 0.009). PGD patients who developed CLAD showed ∼2-times higher %ddcfDNA levels than patients who did not develop CLAD (median [IQR]: 22.4% [11.8, 27.6] vs 9.9% [6.7, 14.9], p = 0.007).
Conclusion
PGD patients demonstrated increased early posttransplant allograft injury, as measured by %ddcfDNA, in comparison to non-PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone.

Published by Elsevier Inc.

J Heart Lung Transplant: 30 May 2021; 40:488-493
Keller M, Bush E, Diamond JM, Shah P, ... Jang M, Agbor-Enoh S
J Heart Lung Transplant: 30 May 2021; 40:488-493 | PMID: 33814284
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bone marrow-derived AXL tyrosine kinase promotes mitogenic crosstalk and cardiac allograft vasculopathy.

Glinton K, DeBerge M, Fisher E, Schroth S, ... Luo X, Thorp EB
Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. AXL protein is found on multiple cell types, including bone marrow-derived myeloid cells. The causal role of AXL from this compartment and during transplant is largely unknown. This is important because AXL is a key regulator of myeloid inflammation. Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene, we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. Co-culture experiments designed to identify cell-intrinsic functions of Axl uncovered complementary cell-proliferative pathways by which Axl promotes CAV-associated inflammation. Specifically, Axl-deficient myeloid cells were less efficient at increasing the replication of both antigen-specific T cells and vascular smooth muscle cells (VSMCs), the latter a key hallmark of CAV. For the latter, we discovered that Axl-was required to amass the VSMC mitogen Platelet-Derived Growth Factor. Taken together, our studies reveal a new role for myeloid Axl in the progression of CAV and mitogenic crosstalk. Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:435-446
Glinton K, DeBerge M, Fisher E, Schroth S, ... Luo X, Thorp EB
J Heart Lung Transplant: 30 May 2021; 40:435-446 | PMID: 33846079
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

Lentine KL, Salvalaggio PR, Caliskan Y, Lam NN, ... Kasiske BL, Schnitzler MA
Background
Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described.
Methods
We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, LCLaHRUCL).
Results
Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, 1.392.123.21), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, 1.061.772.96). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, 1.171.501.92 to level 4: aHR, 1.562.012.59). These effects were independent, and interactions were not detected.
Conclusions
Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:513-524
Lentine KL, Salvalaggio PR, Caliskan Y, Lam NN, ... Kasiske BL, Schnitzler MA
J Heart Lung Transplant: 30 May 2021; 40:513-524 | PMID: 33846078
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Use of metabolomics to identify strategies to improve and prolong ex vivo lung perfusion for lung transplants.

Shin J, Hsin MK, Baciu C, Chen Y, ... Keshavjee S, Liu M
Background
Normothermic ex vivo lung perfusion (EVLP) allows for functional assessment of donor lungs; thus has increased the use of marginal lungs for transplantation. To extend EVLP for advanced organ reconditioning and regenerative interventions, cellular metabolic changes need to be understood. We sought to comprehensively characterize the dynamic metabolic changes of the lungs during EVLP, and to identify strategies to improve EVLP.
Methods
Human donor lungs (n = 50) were assessed under a 4-hour Toronto EVLP protocol. EVLP perfusate was sampled at first (EVLP-1h) and fourth hour (EVLP-4h) of perfusion and were submitted for mass spectrometry-based untargeted metabolic profiling. Differentially expressed metabolites between the 2 timepoints were identified and analyzed from the samples of lungs transplanted post-EVLP (n = 42) to determine the underlying molecular mechanisms.
Results
Of the total 312 detected metabolites, 84 were up-regulated and 103 were down-regulated at EVLP-4h relative to 1h (FDR adjusted p < .05, fold change ≥ |1.1|). At EVLP-4h, markedly decreased energy substrates were observed, accompanied by the increase in fatty acid β-oxidation. Concurrently, accumulation of amino acids and nucleic acids was evident, indicative of increased protein and nucleotide catabolism. The uniform decrease in free lysophospholipids and polyunsaturated fatty acids at EVLP-4h suggests cell membrane remodeling.
Conclusions
Untargeted metabolomics revealed signs of energy substrate consumption and metabolic by-product accumulation under current EVLP protocols. Strategies to supplement nutrients and to maintain homeostasis will be vital in improving the current clinical practice and prolonging organ perfusion for therapeutic application to further enhance donor lung utilization.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; 40:525-535
Shin J, Hsin MK, Baciu C, Chen Y, ... Keshavjee S, Liu M
J Heart Lung Transplant: 30 May 2021; 40:525-535 | PMID: 33849769
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cell-free DNA beyond a biomarker for rejection: Biological trigger of tissue injury and potential therapeutics.

Tsuji N, Agbor-Enoh S
Cell-free DNA, measured as donor-derived cell-free DNA is developed as a non-specific biomarker for allograft injury and transplant rejection. However, cell-free DNA characteristics are more specific, its fragment length, nucleotide content, and composition, as well as the tissue source of origin, are intrinsically linked to the underlying disease pathogenesis, showing distinct features in acute cellular rejection and antibody-mediated rejection for example. Further, cell-free DNA and cell-free mitochondrial DNA can directly trigger tissue injury as damage-associated molecular patterns through three major intracellular receptors, toll-like receptor 9 , cyclic guanosine monophosphate-adenosine monophosphate synthase, and inflammasomes (i.e., absent in melanoma 2: AIM2). Therefore, in addition to its role as a non-specific marker for allograft injury, cell-free DNA analysis may be used to phenotype transplant rejection, and to non-invasively point the underlying molecular mechanisms with allograft injury. Novel treatment approaches targeting these cell-free DNA pathways may be useful to treat transplant rejection and prevent end-organ dysfunction. In this review, we discuss the link between cell-free DNA characteristics and disease, the role of cell-free DNA as a damage-associated molecular pattern, and novel therapeutics targeting these cell-free DNA molecular pathways and their potential utility to treat transplant rejection.

Published by Elsevier Inc.

J Heart Lung Transplant: 30 May 2021; 40:405-413
Tsuji N, Agbor-Enoh S
J Heart Lung Transplant: 30 May 2021; 40:405-413 | PMID: 33926787
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association between chronic lung allograft dysfunction and human Cytomegalovirus UL40 peptide variants in lung-transplant recipients.

Vietzen H, Hartenberger S, Jaksch P, Puchhammer-Stöckl E
Natural-Killer cells play an important role in the pathogenesis of chronic lung allograft dysfunction (CLAD) in lung-transplant recipients. Activating NKG2C+ and inhibitory NKG2A+ NK cells proliferate in response to human Cytomegalovirus (HCMV) infection via the presentation of virally encoded UL40 peptides on HLA-E molecules. We aimed to clarify whether infection with HCMV strains carrying different UL40 peptide variants is associated with the development of CLAD. We included 82 lung-transplant recipients, 18 patients developing CLAD and 64 matched control patients without CLAD. In all patients 1 episode of high-level HCMV-replication occurred. HCMV UL40 variants and Natural-Killer-cell proliferation with distinct UL40 peptides were assessed. The VMTPRTLIL variant was significantly overrepresented in patients developing CLAD (p < 0.0001) and lead to a significantly lower proliferation of inhibitory NKG2A+ cells, compared to the VMAPRTLIL, VMAPRTLVL and VMAPRTLLL variants (p < 0.0001). Thus, HCMV UL40 variants may contribute to development of CLAD over the NK cell response.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; epub ahead of print
Vietzen H, Hartenberger S, Jaksch P, Puchhammer-Stöckl E
J Heart Lung Transplant: 30 May 2021; epub ahead of print | PMID: 34183227
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes of pre- heart transplantation desensitization in a series of highly sensitized patients bridged with left ventricular assist devices.

Saadi TA, Lawrecki T, Narang N, Joshi A, ... Cotts W, Andrade A
Desensitization therapy for heart transplantation (HT) candidates can shorten transplant wait times and broaden the donor pool. Specific evidence-based recommendations on both protocols and indications are lacking. We retrospectively assessed left ventricular assist devices-bridged candidates who received pre-HT desensitization therapy. The therapeutic protocol consisted of intravenous immunoglobulin and rituximab followed by bortezomib and plasmapheresis if an insufficient response was achieved. Desensitization was attempted in 10 patients; only 7 tolerated therapy and underwent transplant. For those patients, median decrease in unacceptable calculated panel reactive antibody was 11%; there was no significant decrease for 3 patients. Post-desensitization adverse events were observed in all patients which included coagulopathy, bone marrow suppression, and infection. Median time to first infection was 16 days. One patient had clinically significant rejection and 3 patients had uptrending donor-specific antibodies. Decisions to proceed with desensitization should be individualized understanding potential risks and benefits.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 May 2021; epub ahead of print
Saadi TA, Lawrecki T, Narang N, Joshi A, ... Cotts W, Andrade A
J Heart Lung Transplant: 30 May 2021; epub ahead of print | PMID: 34281777
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies.

Divithotawela C, Pham A, Bell PT, Ledger EL, ... Wells TJ, Chambers DC
Background
Chronic Lung Allograft Dysfunction (CLAD) limits long-term survival following lung transplantation. Colonization of the allograft by Pseudomonas aeruginosa is associated with an increased risk of CLAD and inferior overall survival. Recent experimental data suggests that \'cloaking\' antibodies targeting the O-antigen of the P. aeruginosa lipopolysaccharide cell wall (cAbs) attenuate complement-mediated bacteriolysis in suppurative lung disease.
Methods
In this retrospective cohort analysis of 123 lung transplant recipients, we evaluated the prevalence, risk factors and clinical impact of serum cAbs following transplantation.
Results
cAbs were detected in the sera of 40.7% of lung transplant recipients. Cystic fibrosis and younger age were associated with increased risk of serum cAbs (CF diagnosis, OR 6.62, 95% CI 2.83-15.46, p < .001; age at transplant, OR 0.69, 95% CI 0.59-0.81, p < .001). Serum cAbs and CMV mismatch were both independently associated with increased risk of CLAD (cAb, HR 4.34, 95% CI 1.91-9.83, p < .001; CMV mismatch (D+/R-), HR 5.40, 95% CI 2.36-12.32, p < .001) and all-cause mortality (cAb, HR 2.75, 95% CI 1.27-5.95, p = .010, CMV mismatch, HR 3.53, 95% CI 1.62-7.70, p = .002) in multivariable regression analyses.
Conclusions
Taken together, these findings suggest a potential role for \'cloaking\' antibodies targeting P. aeruginosa LPS O-antigen in the immunopathogenesis of CLAD.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 May 2021; epub ahead of print
Divithotawela C, Pham A, Bell PT, Ledger EL, ... Wells TJ, Chambers DC
J Heart Lung Transplant: 29 May 2021; epub ahead of print | PMID: 34226118
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bronchoalveolar lavage cytokine-based risk stratification of minimal acute rejection in clinically stable lung transplant recipients.

Levy L, Huszti E, Ahmed M, Ghany R, ... Juvet S, Martinu T
Background
Acute cellular rejection (ACR) remains the most significant risk factor for chronic lung allograft dysfunction (CLAD). While clinically significant or higher-grade (≥A2) ACR is generally treated with augmented immunosuppression (IS), the management of clinically stable grade A1 ACR remains controversial. At our center, patients with clinically stable grade A1 ACR are routinely not treated with augmented IS. While the overall outcomes in this group of patients at our center are equivalent to patients with stable A0 pathology, CLAD and death rates remain overall high. We hypothesized that a distinct cytokine signature at the time of early minimal rejection state would be associated with worse outcomes. Specifically, we aimed to determine whether bronchoalveolar lavage (BAL) biomarkers at the time of first clinically stable grade A1 ACR (CSA1R) are predictive of subsequent CLAD or death.
Methods
Among all adult, bilateral, first lung transplants, performed 2010-2016, transbronchial biopsies obtained within the first-year post-transplant were categorized as clinically stable or unstable based on the presence or absence of ≥10% concurrent drop in forced expiratory volume in 1 second (FEV1). We assessed BAL samples obtained at the time of CSA1R episodes, which were not preceded by another ACR (i.e., first episodes). Twenty-one proteins previously associated with ACR or CLAD were measured in the BAL using a multiplex bead assay. Association between protein levels and subsequent CLAD or death was assessed using Cox Proportional Hazards models, adjusted for relevant peri-transplant clinical covariates.
Results
We identified 75 patients with first CSA1R occurring at a median time of 98 days (range 48.5-197) post-transplant. Median time from transplant to CLAD or death was 1247 (756.5-1921.5) and 1641 days (1024.5-2326.5), respectively. In multivariable models, levels of MCP1/CCL2, S100A8, IL10, TNF-receptor 1, and pentraxin 3 (PTX3) were associated with both CLAD development and death (p < 0.05 for all). PTX3 remained significantly associated with both CLAD and death after adjusting for multiple comparisons.
Conclusion
Our data indicate that a focused BAL protein signature, with PTX3 having the strongest association, may be useful in determining a subset of CSA1R patients at increased risk and may benefit from a more aggressive management strategy.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 May 2021; epub ahead of print
Levy L, Huszti E, Ahmed M, Ghany R, ... Juvet S, Martinu T
J Heart Lung Transplant: 28 May 2021; epub ahead of print | PMID: 34215500
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Implantable cardioverter defibrillators in left ventricular assist device patients: Α systematic review and meta-analysis.

Rorris FP, Antonopoulos CN, Kyriakopoulos CP, Drakos SG, Charitos C
Implantable cardioverter-defibrillators (ICDs) remain the standard of care in advanced heart failure with reduced ejection fraction patients for the prevention of sudden cardiac death. However, current guidelines remain conflicting with respect to the use of ICDs in patients supported with a continuous flow left ventricular assist device (CF-LVAD). The current review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies comparing the use of ICD in patients with CF-LVADs were included. The 2 primary outcomes studied were all-cause mortality, and a successful bridge to heart transplantation. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs). We also compared baseline characteristics between US and European studies, for CF-LVAD patients with an ICD. Among all studies, the use of an ICD was not associated with all-cause mortality in patients with CF-LVADs (OR: 0.85, 95% CIs: 0.64-1.12, p = 0.24). The presence of an ICD was associated with a trend towards increased likelihood of successful bridge to heart transplantation (OR: 1.12, 95% CI: 1.0-1.3, p = 0.06). A subgroup analysis of studies published by European centers revealed a significant decrease in pooled mortality (OR: 0.58, 95% CI: 0.4-0.83, p = 0.003) with the use of ICD, contrary to an increase in pooled mortality among studies published by US centers (OR: 1.2, 95% CI 1.02-1.33, p = 0.025). Moreover, we identified significant differences in baseline characteristics such as bridge to transplantation rate, Interagency Registry for Mechanically Assisted Circulatory Support profiles, and use of an intra-aortic balloon pump or extracorporeal membrane oxygenation preoperatively, between the US and European populations. While this meta-analysis did not show an overall survival benefit with the use of an ICD in CF-LVAD patients, it revealed significant differences in the derived benefit, in distinct patient populations. This might reflect differences in baseline patient characteristics and warrants further investigation.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 May 2021; epub ahead of print
Rorris FP, Antonopoulos CN, Kyriakopoulos CP, Drakos SG, Charitos C
J Heart Lung Transplant: 28 May 2021; epub ahead of print | PMID: 34176727
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Increasing multiorgan heart transplantation with hepatitis C virus donors in the current-era.

Madan S, Patel SR, Vlismas P, Hemmige V, ... Goldstein DJ, Jorde UP
The trends and outcomes of multiorgan heart-transplantation (HT) using hepatitis C virus (HCV) donors in the contemporary era are sparsely known. Using UNOS registry, 1322 adult multiorgan-HTs (n = 986 heart-kidney, n = 155 heart-lung, n = 181 heart-liver) between August-2015 and August-2020 were identified, of which 109 were performed using HCV-donors (n = 77 HCV nucleic-acid-amplification testing [NAT] positive irrespective of antibody status [HCV-viremic]; and n = 32 HCV Ab+/NAT-[HCV antibody + nonviremic]). The percentage of HCV-donors used for multiorgan-HT increased from 0% in 2015 to 14% in 2020 (p < 0.001), but there was wide variation across UNOS regions and center volumes. Recipients of multiorgan heart-kidney transplants from HCV-donors (n = 90) and HCV-naïve (HCV Ab-/NAT-) donors (n = 896) had similar 1-year survival using unadjusted and adjusted Cox-proportional hazards-regression models including in propensity-score matched cohorts. Post-HT rates of cardiac-allograft-vasculopathy (5.4% vs 5.8%) and chronic-dialysis (7.3% vs 4.9%) at 1-year were also similar. Use of HCV-donors (HCV-viremic, HCV Ab+ nonviremic) for multiorgan-HT has increased significantly. Encouraging 1-year outcomes in heart-kidney recipients from HCV-donors should support further expansion of heart-kidney transplantation using HCV-donors.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 May 2021; epub ahead of print
Madan S, Patel SR, Vlismas P, Hemmige V, ... Goldstein DJ, Jorde UP
J Heart Lung Transplant: 28 May 2021; epub ahead of print | PMID: 34176726
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Intraoperative anti-A/B immunoadsorption is associated with significantly reduced blood product utilization with similar outcomes in pediatric ABO-incompatible heart transplantation.

Issitt R, Booth J, Crook R, Robertson A, ... Burch M, Fenton M
Background
Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible heart transplantation. Here we report the first case series of patients transplanted with ABO-IA, and compare outcomes with those undergoing plasma exchange facilitated ABO-incompatible heart transplantation (ABO-PE).
Methods
Data were retrospectively analysed on all ABO-incompatible heart transplants undertaken at a single centre between January 1, 2000 and June 1, 2020. Data included all routine laboratory tests, demographics and pre-operative characteristics, intraoperative details and post-operative outcomes. Primary outcome measures were volume of blood product transfusions, maximum post-transplant isohaemagglutinin titres, occurrence of rejection and graft survival. Secondary outcome measures were length of intensive care and hospital stay. Demographic and survival data were also obtained for ABO-compatible transplants during the same time period for comparison.
Results
Thirty-seven patients underwent ABO-incompatible heart transplantation, with 27 (73%) using ABO-PE and 10 (27%) using ABO-IA. ABO-IA patients were significantly older than ABO-PE patients (p < 0.001) and the total volume of blood products transfused during the hospital admission was significantly lower (164 [126-212] ml/kg vs 323 [268-379] ml/kg, p < 0.001). No significant differences were noted between methods in either pre or post-transplant maximum isohaemagglutinin titres, incidence of rejection, length of intensive care or total hospital stay. Survival comparison showed no significant difference between antibody reduction methods, or indeed ABO-compatible transplants (p = 0.6).
Conclusions
This novel technique appears to allow a significantly older population than typical to undergo ABO-incompatible heart transplantation, as well as significantly reducing blood product utilization. Furthermore, intraoperative anti-A/B immunoadsorption does not demonstrate increased early post-transplant isohaemagglutinin accumulation or rates of rejection compared to ABO-PE. Early survival is equivalent between ABO-IA, ABO-PE and ABO-compatible heart transplantation.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 May 2021; epub ahead of print
Issitt R, Booth J, Crook R, Robertson A, ... Burch M, Fenton M
J Heart Lung Transplant: 28 May 2021; epub ahead of print | PMID: 34187714
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Aspiration of conjugated bile acids predicts adverse lung transplant outcomes and correlates with airway lipid and cytokine dysregulation.

Urso A, Leiva-Juárez MM, Briganti DF, Aramini B, ... Cremers S, D\'Ovidio F
Introduction
Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes.
Methods
Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections.
Results
Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines.
Conclusions
Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 May 2021; epub ahead of print
Urso A, Leiva-Juárez MM, Briganti DF, Aramini B, ... Cremers S, D'Ovidio F
J Heart Lung Transplant: 27 May 2021; epub ahead of print | PMID: 34183226
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients.

Havlin J, Svorcova M, Dvorackova E, Lastovicka J, ... Kalina T, Hubacek P
The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 20 May 2021; epub ahead of print
Havlin J, Svorcova M, Dvorackova E, Lastovicka J, ... Kalina T, Hubacek P
J Heart Lung Transplant: 20 May 2021; epub ahead of print | PMID: 34120839
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cerebral vasoreactivity in HeartMate 3 patients.

Stöhr EJ, Ji R, Akiyama K, Mondellini G, ... McDonnell BJ, Willey JZ
Background
While rates of stroke have declined with the HeartMate3 (HM3) continuous- flow (CF) left ventricular assist device (LVAD), the impact of non-pulsatile flow and artificial pulse physiology on cerebrovascular function is not known. We hypothesized that improved hemodynamics and artificial pulse physiology of HM3 patients would augment cerebrovascular metabolic reactivity (CVR) compared with HeartMate II (HMII) CF-LVAD and heart failure (HF) patients.
Methods
Mean, peak systolic and diastolic flow velocities (MFV, PSV, MinFV, respectively) and cerebral pulsatility index were determined in the middle cerebral artery (MCA) before and after a 30 sec breath-hold challenge in 90 participants: 24 healthy controls; 30 HF, 15 HMII, and 21 HM3 patients.
Results
In HM3 patients, breath-holding increased MFV (Δ8 ± 10 cm/sec, p < .0001 vs baseline) to levels similar to HF patients (Δ9 ± 8 cm/sec, p > .05), higher than HMII patients (Δ2 ± 8 cm/sec, p < .01) but lower than healthy controls (Δ13 ± 7 cm/sec, p < .05). CF-LVAD altered the proportion of systolic and diastolic flow responses as reflected by a differential cerebral pulsatility index (p = .03). Baseline MFV was not related to CVR (r2 = 0.0008, p = .81). However, CF-LVAD pump speed was strongly inversely associated with CVR in HM II (r2 = 0.51, p = .003) but not HM3 patients (r2 = 0.01, p = .65).
Conclusions
Compared with HMII, HM3 patients have a significantly improved CVR. However, CVR remains lower in HM3 and HF patients than in healthy controls, therefore suggesting that changes in cerebral hemodynamics are not reversed by CF-LVAD therapy. Further research on the mechanisms and the long-term impact of altered cerebral hemodynamics in this unique patient population are warranted.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 20 May 2021; epub ahead of print
Stöhr EJ, Ji R, Akiyama K, Mondellini G, ... McDonnell BJ, Willey JZ
J Heart Lung Transplant: 20 May 2021; epub ahead of print | PMID: 34134913
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes.

Genuardi MV, Moss N, Najjar SS, Houston BA, ... Tedford RJ, Birati EY
Background
COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.
Methods
We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.
Results
The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.
Conclusions
We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 May 2021; epub ahead of print
Genuardi MV, Moss N, Najjar SS, Houston BA, ... Tedford RJ, Birati EY
J Heart Lung Transplant: 18 May 2021; epub ahead of print | PMID: 34140222
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term survival in patients with post-LVAD right ventricular failure: multi-state modelling with competing outcomes of heart transplant.

Shad R, Fong R, Quach N, Bowles C, ... Teuteberg J, Hiesinger W
Background
Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation.
Methods
We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model.
Results
Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p = < .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p = .4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without.

Conclusions:
and relevance
Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 May 2021; epub ahead of print
Shad R, Fong R, Quach N, Bowles C, ... Teuteberg J, Hiesinger W
J Heart Lung Transplant: 18 May 2021; epub ahead of print | PMID: 34167863
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical characteristics, management practices, and outcomes among lung transplant patients with COVID-19.

Mohanka MR, Mahan LD, Joerns J, Lawrence A, ... Torres F, Banga A
Background
There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy.
Methods
We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36).
Results
As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%).
Conclusions
Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 17 May 2021; epub ahead of print
Mohanka MR, Mahan LD, Joerns J, Lawrence A, ... Torres F, Banga A
J Heart Lung Transplant: 17 May 2021; epub ahead of print | PMID: 34172387
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

HLA-DRB1 mismatch-based identification of donor-derived cell free DNA (dd-cfDNA) as a marker of rejection in heart transplant recipients: A single-institution pilot study.

Sorbini M, Togliatto GM, Simonato E, Boffini M, ... Vaisitti T, Deaglio S
Background
Donor-derived cell-free DNA (dd-cfDNA) is considered a reliable marker of organ damage with potential applications in the follow-up of transplant recipients.
Methods
In this work we present an assay based on the donor-recipient HLA-mismatch (human leukocyte antigen) at the HLA-DRB1 locus to monitor rejection by quantifying the percentage of dd-cfDNA using a droplet digital PCR (polymerase chain reaction) technique. A panel of probes targeting the HLA-DRB1 locus and covering >85% genetic variability was validated and used to assess dd-cfDNA levels in a prospective cohort of 19 adult heart transplant recipients (mean age 50.9±14.8 years). The assay was carried out on a total of 232 liquid biopsies collected at the same time as endomyocardial biopsy (EMB) during routine post-transplant follow-up.
Results
Results show a significant increase of dd-cfDNA related to ischemia-reperfusion injury (2.22±2.09%) and to acute cellular rejection (1.71±3.10%) compared to stable conditions (0.43±1.04%, p < 0.0001). On the contrary, no increase was observed during infections or vascular complications, underlining the potential role of this biomarker for rejection monitoring. With a cut-off of 0.11%, the test showed 70.8% specificity (95% CI, 58.17% - 81.40%) and 64.2% sensitivity (95% CI, 49.80% - 76.86%) in discriminating acute rejection from no rejection.
Conclusions
These data demonstrate that this HLA mismatch-based droplet digital PCR method is effective for monitoring rejection in heart transplant recipients. Compared to next generation sequencing approaches, it is far more flexible, less expensive and provides faster results.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 13 May 2021; epub ahead of print
Sorbini M, Togliatto GM, Simonato E, Boffini M, ... Vaisitti T, Deaglio S
J Heart Lung Transplant: 13 May 2021; epub ahead of print | PMID: 34134912
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Assessing predicted heart mass size matching in obese heart transplant recipients.

Kim ST, Helmers MR, Iyengar A, Smood B, ... Altshuler P, Atluri P
Background
Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging. We examined the use of PHM undersized hearts in obese recipients and assessed its impact on survival.
Methods
The United Network for Organ Sharing database was queried for adult patients undergoing heart transplantation from 1995 to 2020. Obese recipients (BMI ≥ 30) were categorized based on donor-recipient PHM match ≤-20% (undersized) or >-20% (size-matched). Nearest-neighbor propensity score matching was performed to adjust for baseline differences between cohorts. Temporal outcomes were compared by Kaplan-Meier survival analysis.
Results
A total of 13,668 obese recipients met inclusion criteria, with 9.6% receiving undersized and 90.4% receiving size-matched hearts. The proportion of undersized donor hearts in obese recipients significantly decreased over the study period (16.2% [1995] to 7.4% [2019], NP-trend < 0.001). Propensity-score matching resulted in 984 well-matched pairs of undersized and size-matched obese recipients. Recipients of undersized hearts saw similar 30-day mortality (5.5% vs 6.0%, p= 0.11) and re-transplantation rates (1.2% vs 1.2%, p = 1.00) as size-matched recipients. Survival at 1 year (88.4% vs 87.9%, p = 0.14), and 15 years (35.1% vs 31.0%, p = 0.12) was similar across cohorts.
Conclusions
A decreasing proportion of PHM undersized hearts are being utilized in obese recipients. However, utilizing PHM undersized hearts in obese recipients was not associated with a detriment in survival.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 May 2021; epub ahead of print
Kim ST, Helmers MR, Iyengar A, Smood B, ... Altshuler P, Atluri P
J Heart Lung Transplant: 11 May 2021; epub ahead of print | PMID: 34127356
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Immune response to COVID-19 in older adults.

Jergović M, Coplen CP, Uhrlaub JL, Nikolich-Žugich J
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third highly pathogenic coronavirus to emerge in the human population in last two decades. SARS-CoV-2 spread from Wuhan, China, across the globe, causing an unprecedented public healthcare crisis. The virus showed remarkable age dependent pathology, with symptoms resembling common cold in most adults and children while causing more severe respiratory distress and significant mortality in older and frail humans. Even before the SARS-CoV-2 outbreak infectious diseases represented one of the major causes of death of older adults. Loss of immune function and reduced protection from infectious agents with age - immunosenescence - is a result of complex mechanisms affecting production and maintenance of immune cells as well as the initiation, maintenance and termination of properly directed immune responses. Here we briefly discuss the current knowledge on how this process affects age-dependent outcomes of SARS-CoV-2 infection.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 10 May 2021; epub ahead of print
Jergović M, Coplen CP, Uhrlaub JL, Nikolich-Žugich J
J Heart Lung Transplant: 10 May 2021; epub ahead of print | PMID: 34140221
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A prospective French multicenter cohort.

Dauriat G, Reynaud-Gaubert M, Cottin V, Lamia B, ... Laouenan C, Mal H
Background
A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype.
Methods
We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point.
Results
From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months.
Conclusions
Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 10 May 2021; epub ahead of print
Dauriat G, Reynaud-Gaubert M, Cottin V, Lamia B, ... Laouenan C, Mal H
J Heart Lung Transplant: 10 May 2021; epub ahead of print | PMID: 34218966
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Therapeutic efficacy of large aligned cardiac tissue derived from induced pluripotent stem cell in a porcine ischemic cardiomyopathy model.

Suzuki K, Miyagawa S, Liu L, Kawamura T, ... Kawamura A, Sawa Y
Background
Although induced pluripotent stem (iPS) cell-derived cardiac constructs may have a potential in cardiomyogenesis of a distressed myocardium, obtaining polarity in cardiac constructs, such as via myocyte alignment, may be crucial to achieve a maximum contractile force for better clinical outcomes. We herein hypothesized that transplantation of an aligned cardiac tissue derived from iPS cells has therapeutic effects in a porcine ischemic cardiomyopathy model as a preclinical trial.
Methods
Aligned cardiac tissues were developed by culturing high-purity iPS cell-derived cardiomyocytes in xeno-free conditions and transplanting them into infarct porcine hearts (iPS-CM group, n = 7; control, n = 6). Three months after treatment, therapeutic efficacy was evaluated functionally and histologically.
Results
In vitro assessment revealed that the aligned cardiac tissue containing high purity cardiomyocytes contracted homogeneously and had excellent mechanical properties. In the in vivo study, the left ventricular ejection fraction of the iPS-CM group was significantly greater than that of the control group, 3 months after transplantation (37.8% ± 2.3% vs 28.3% ± 2.5%, p < 0.05). Pathologically, attenuated interstitial fibrosis, attenuation of hypertrophied cardiomyocytes, and an increased capillary density were also prominent in the iPS-CM group. A limited amount of engraftment of the transplanted tissue maintaining tissue alignment was observed at 2 weeks after transplantation.
Conclusions
The creation of large-scale functional aligned cardiac tissue was feasible, and the transplantation of the aligned tissue improved cardiac function with angiogenesis and antifibrotic effects in a porcine cardiomyopathy model.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 07 May 2021; epub ahead of print
Suzuki K, Miyagawa S, Liu L, Kawamura T, ... Kawamura A, Sawa Y
J Heart Lung Transplant: 07 May 2021; epub ahead of print | PMID: 34108109
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The lung microbiome in lung transplantation.

McGinniss JE, Whiteside SA, Simon-Soro A, Diamond JM, ... Bushman FD, Collman RG
Culture-independent study of the lower respiratory tract after lung transplantation has enabled an understanding of the microbiome - that is, the collection of bacteria, fungi, and viruses, and their respective gene complement - in this niche. The lung has unique features as a microbial environment, with balanced entry from the upper respiratory tract, clearance, and local replication. There are many pressures impacting the microbiome after transplantation, including donor allograft factors, recipient host factors such as underlying disease and ongoing exposure to the microbe-rich upper respiratory tract, and transplantation-related immunosuppression, antimicrobials, and postsurgical changes. To date, we understand that the lung microbiome after transplant is dysbiotic; that is, it has higher biomass and altered composition compared to a healthy lung. Emerging data suggest that specific microbiome features may be linked to host responses, both immune and non-immune, and clinical outcomes such as chronic lung allograft dysfunction (CLAD), but many questions remain. The goal of this review is to put into context our burgeoning understanding of the lung microbiome in the postlung transplant patient, the interactions between microbiome and host, the role the microbiome may play in post-transplant complications, and critical outstanding research questions.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 06 May 2021; epub ahead of print
McGinniss JE, Whiteside SA, Simon-Soro A, Diamond JM, ... Bushman FD, Collman RG
J Heart Lung Transplant: 06 May 2021; epub ahead of print | PMID: 34120840
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

First lung and kidney multi-organ transplant following COVID-19 Infection.

Guenthart BA, Krishnan A, Alassar A, Madhok J, ... Dhillon GS, Woo YJ
As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 01 May 2021; epub ahead of print
Guenthart BA, Krishnan A, Alassar A, Madhok J, ... Dhillon GS, Woo YJ
J Heart Lung Transplant: 01 May 2021; epub ahead of print | PMID: 34059432
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The impact of donor sex on heart transplantation outcomes-a study of over 60,000 patients in the United States.

Zhu Y, Shudo Y, Lingala B, Joseph Woo Y
Background
The impact of donor sex on heart transplantation outcomes irrespective of recipient sex remains unclear. The objective of this study was to evaluate the impact of donor sex on heart transplantation outcomes in the United States.
Methods
From 1987 to March 2019, 63,775 adult patients who underwent heart transplantation were matched to 27,509 male and 11,474 female donors in the United States. Data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor sex and donor menopause status. The groups were matched 1:1 using the propensity score of each patient. Kaplan-Meier survival and cox proportional hazards regression analyses were performed. The primary endpoint was all-cause mortality. Secondary endpoints were postoperative complications.
Results
Propensity matching generated 15,506 and 1,094 patients based on donor sex and menopause status, respectively. Recipients who received female donor allografts were more likely to have acute rejection episodes requiring anti-rejection medical treatment (11.9% vs 10.1%, p = .007) and require post-transplant dialysis (10.9% vs 9.3%, p = .001) than those who received male donor allografts. Overall survival using female vs male donor allografts was similar (p = .34). Recipients who received pre- vs post-menopausal female donor hearts had similar postoperative outcomes and overall survival (p = .23).
Conclusions
Analysis of the UNOS database showed similar median survival using female vs male donor hearts in adult heart transplantation, irrespective of donor menopause status. Female donor allografts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Apr 2021; epub ahead of print
Zhu Y, Shudo Y, Lingala B, Joseph Woo Y
J Heart Lung Transplant: 30 Apr 2021; epub ahead of print | PMID: 34083118
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Native lung complications after living-donor lobar lung transplantation.

Mineura K, Chen-Yoshikawa TF, Tanaka S, Yamada Y, ... Menju T, Date H
Background
Living-donor lobar lung transplantation (LDLLT) is viable for critically ill patients in situations of donor shortage. Because it is sometimes difficult to find 2 ideal living donors with suitable graft sizes, we developed native lung-sparing procedures, including single LDLLT and native upper lobe-sparing LDLLT. This study aimed to investigate native lung complications (NLCs) in native lung-sparing LDLLT.
Methods
Between April 2002 and March 2019, 92 LDLLTs and 124 cadaveric lung transplantations (CLTs) were performed at the Kyoto University Hospital. Our prospectively maintained database and clinical records were reviewed to compare NLCs among recipients who underwent native lung-sparing LDLLT (n = 21) with those among recipients who underwent single CLT (n = 61).
Results
Among 21 recipients who underwent native lung-sparing LDLLT, 11 NLCs occurred in 8 recipients. No fatal NLC was noted; however, 2 required surgical intervention. Post-transplant survival was not significantly different between native lung-sparing LDLLT recipients with NLCs and those without NLCs. The incidence of NLCs was comparable between native lung-sparing LDLLT recipients and single CLT recipients (8/21 vs 26/61, p = 0.80); however, NLCs occurred significantly later in LDLLT recipients than in CLT recipients (median: 665 vs 181.5 days after transplantation, p = 0.014).
Conclusions
NLCs after native lung-sparing LDLLT had favorable outcomes. Therefore, native lung-sparing LDLLT is a useful treatment option for severely ill patients who cannot wait for CLT. However, it is important to recognize that NLCs may occur later in LDLLT than in CLT.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:343-350
Mineura K, Chen-Yoshikawa TF, Tanaka S, Yamada Y, ... Menju T, Date H
J Heart Lung Transplant: 29 Apr 2021; 40:343-350 | PMID: 33602629
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial.

Brautaset Englund KV, Østby CM, Rolid K, Gude E, ... Gullestad L, Broch K
Aims
Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients.
Methods and results
This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39).
Conclusion
Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%.
Trial registration number
http//www.clinicaltrials.gov identifier NCT03662789.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:359-367
Brautaset Englund KV, Østby CM, Rolid K, Gude E, ... Gullestad L, Broch K
J Heart Lung Transplant: 29 Apr 2021; 40:359-367 | PMID: 33612360
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation.

Fessler J, Fischler M, Sage E, Ouattara J, ... Vallee A, Le Guen M
Background
Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors.
Methods
This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients.
Results
Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028).
Conclusions
OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:334-342
Fessler J, Fischler M, Sage E, Ouattara J, ... Vallee A, Le Guen M
J Heart Lung Transplant: 29 Apr 2021; 40:334-342 | PMID: 33632637
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk of primary graft dysfunction following lung transplantation in selected adults with connective tissue disease-associated interstitial lung disease.

Natalini JG, Diamond JM, Porteous MK, Lederer DJ, ... Kawut SM, Bernstein EJ
Background
Previous studies have reported similarities in long-term outcomes following lung transplantation for connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis (IPF). However, it is unknown whether CTD-ILD patients are at increased risk of primary graft dysfunction (PGD), delays in extubation, or longer index hospitalizations following transplant compared to IPF patients.
Methods
We performed a multicenter retrospective cohort study of CTD-ILD and IPF patients enrolled in the Lung Transplant Outcomes Group registry who underwent lung transplantation between 2012 and 2018. We utilized mixed effects logistic regression and stratified Cox proportional hazards regression to determine whether CTD-ILD was independently associated with increased risk for grade 3 PGD or delays in post-transplant extubation and hospital discharge compared to IPF.
Results
A total of 32.7% (33/101) of patients with CTD-ILD and 28.9% (145/501) of patients with IPF developed grade 3 PGD 48-72 hours after transplant. There were no significant differences in odds of grade 3 PGD among patients with CTD-ILD compared to those with IPF (adjusted OR 1.12, 95% CI 0.64-1.97, p = 0.69), nor was CTD-ILD independently associated with a longer post-transplant time to extubation (adjusted HR for first extubation 0.87, 95% CI 0.66-1.13, p = 0.30). However, CTD-ILD was independently associated with a longer post-transplant hospital length of stay (median 23 days [IQR 14-35 days] vs17 days [IQR 12-28 days], adjusted HR for hospital discharge 0.68, 95% CI 0.51-0.90, p = 0.008).
Conclusion
Patients with CTD-ILD experienced significantly longer postoperative hospitalizations compared to IPF patients without an increased risk of grade 3 PGD.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:351-358
Natalini JG, Diamond JM, Porteous MK, Lederer DJ, ... Kawut SM, Bernstein EJ
J Heart Lung Transplant: 29 Apr 2021; 40:351-358 | PMID: 33637413
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Systemic ventricular assist device support in Fontan patients: A report by ACTION.

Cedars A, Kutty S, Danford D, Schumacher K, ... Villa C, Zinn M
Background
The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients.
Methods
We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation.
Results
We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals.
Conclusions
VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:368-376
Cedars A, Kutty S, Danford D, Schumacher K, ... Villa C, Zinn M
J Heart Lung Transplant: 29 Apr 2021; 40:368-376 | PMID: 33642140
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Spectrum of findings on ventilation‒perfusion lung scintigraphy after lung transplantation and association with outcomes.

Mohanka M, Pinho DF, Garcia H, Kanade R, ... Zhang S, Banga A
Background
Air trapping (AT) is one of the hallmarks of allograft dysfunction after lung transplantation (LT). Inert gas‒based ventilation‒perfusion (VQ) lung scintigraphy has excellent sensitivity in the detection of AT.
Methods
We reviewed the charts of patients who underwent single or double LT between January 2012 and December 2014 (N = 193). Patients without a VQ scintigraphy at the first annual visit (n = 16) and those who did not survive till 1 year (n = 26) were excluded (final n = 151, mean age = 55.8 [SD =14] years, male = 85, female = 66). VQ scintigraphy was independently reviewed and reconciled for the presence and severity of AT by 2 investigators blinded to the clinical data (D.F.P. and D.M.). A 3-year post-transplant survival was the primary end-point.
Results
AT was common (n = 73, 48.3%). Patients with obstructive lung diseases as the underlying diagnosis (adjusted odds ratio [OR], 4.36, 95% CI: 1.64‒11.6; p = 0.003) and those with lower body mass index (BMI) (BMI < 25 kg/m2 and 25‒30 kg/m2; p < 0.001) had an increased risk of developing AT in the allograft. The presence of AT (adjusted OR, 2.33, 95% CI: 1.01‒5.36; p = 0.04) and peak forced expiratory volume in 1 sec (FEV1) <60% predicted during the first year after LT were independently associated with 3-year mortality. The association of AT with post-transplant mortality was the strongest among patients with BMI <30 kg/m2 and peak FEV1 <60% predicted.
Conclusions
The finding of AT on VQ scintigraphy at the first annual visit after LT is independently associated with worse post-transplant mortality. The sub-group of patients who fail to achieve a peak FEV1 of 60% predicted during the first year after LT appears to be the key driver of this association.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:377-386
Mohanka M, Pinho DF, Garcia H, Kanade R, ... Zhang S, Banga A
J Heart Lung Transplant: 29 Apr 2021; 40:377-386 | PMID: 33648871
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Monitoring of perfusion quality and prediction of donor heart function during ex-vivo machine perfusion by myocardial microcirculation versus surrogate parameters.

Saemann L, Wenzel F, Kohl M, Korkmaz-Icöz S, ... Karck M, Szabó G
Currently, lactate (Lac) is used to evaluate machine perfusion (MP) of hearts, donated after circulatory death (DCD). We hypothesize that monitoring of myocardial microcirculation (mLDP) by Laser-Doppler-Perfusion is superior to Lac to evaluate perfusion and predict contractility. In a pig model, DCD-hearts were perfused 4 hours followed by reperfusion and left ventricular contractility measurement. Lac and mLDP were measured every 30 min in successfully (N = 9) and unsuccessfully (N = 7) maintained hearts. Successfully maintained hearts showed decreasing Lac (5.6 to 2.8 mmol/L) and slightly downregulated (92%) mLDP. In unsuccessfully maintained hearts Lac first decreased (5.1 to 3.8 mmol/L) followed by increase and mLDP dropped to 39%. In a single-variable regression only mLDP showed a significant r² for systolic (0.514, p = 0.045) and diastolic (0.501, p = 0.049) parameters. The combination of mLDP and Lac (r2 = 0.876, p = 0.005) showed best results. mLDP seems to be superior to Lac to show perfusion disorders and predict DCD-heart contractility.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:387-391
Saemann L, Wenzel F, Kohl M, Korkmaz-Icöz S, ... Karck M, Szabó G
J Heart Lung Transplant: 29 Apr 2021; 40:387-391 | PMID: 33726982
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study.

Pagani FD, Mehra MR, Cowger JA, Horstmanshof DA, ... Kormos RL, Rogers JG
Background
Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices.
Objectives
Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs.
Methods
Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments.
Results
A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p< 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p < 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p < 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p < 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p < 0.001 (17.4% reduction) and for HeartMate 3 vs Other-VADs was -$17,947, p < 0.001 (26.1% reduction).
Conclusions
In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Apr 2021; 40:323-333
Pagani FD, Mehra MR, Cowger JA, Horstmanshof DA, ... Kormos RL, Rogers JG
J Heart Lung Transplant: 29 Apr 2021; 40:323-333 | PMID: 33744086
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.