Laneshia K Tague,Hephzibah Anthony,Noha N Salama,Ramsey R Hachem,Brian F Gage,Andrew E Gelman
{"title":"An Integrated Sampling Strategy for Therapeutic Mycophenolic Acid Monitoring in Lung Transplant Recipients.","authors":"Laneshia K Tague,Hephzibah Anthony,Noha N Salama,Ramsey R Hachem,Brian F Gage,Andrew E Gelman","doi":"10.1016/j.healun.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.007","url":null,"abstract":"BACKGROUNDMycophenolic Acid (MPA) is the most used anti-proliferative in lung transplantation, but its pharmacokinetic (PK) variability has precluded therapeutic drug monitoring. Both genetic and clinical factors have been implicated in MPA variability. This study aimed to integrate genetic and clinical factors with PK measurements to quantify MPA exposure.METHODSWe performed 12-hour pharmacokinetic analysis on 60 adult lung transplant recipients maintained on MPA for immunosuppression. We genotyped a SLCO1B3 polymorphisms previously associated MPA metabolism and collected relevant clinical data. We calculated area under the curve (AUC0-12) and performed univariate linear regression analysis to evaluate its association with genetic, clinical, and pharmacokinetic variables. We performed lasso regression analysis to create final AUC estimation tools.RESULTSPK-only measurements obtained 2, 3, and 8 hours after MPA administration (C2, C3, and C8) were strongly associated with MPA AUC0-12 (R267%, 67% and 68% respectively). Clinical and genetic factors associated with MPA AUC0-12 included the MPA dose (p = 0.001), transplant diagnosis (p =0.015), SLCO1B3 genotype (p = 0.049), and body surface area (p = 0.050) The best integrated single-sampling strategy included C2 and achieved an R2 value of 80%. The best integrated limited-sampling strategy included C0, C0.25, and C2 and achieved an R2 value of 90%.CONCLUSIONSAn integrated LSS for MPA allows increased accuracy in prediction of MPA AUC0-12 compared to PK-only modelling. Validation of this model will allow for clinically feasible MPA therapeutic drug monitoring and help advance precision management of MPA.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Routine Extracorporeal Cardiopulmonary Resuscitation Service on the Availability of Donor Organs.","authors":"Jana Smalcova,Petra Krupickova,Eva Pokorna,Ondrej Franek,Michal Huptych,Petra Kavalkova,Martin Balik,Jan Malik,Ondrej Smid,Eva Svobodova,Roman Keleman,Jan Belohlavek","doi":"10.1016/j.healun.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.009","url":null,"abstract":"In refractory cardiac arrest, extracorporeal cardiopulmonary resuscitation may increase the survival chance. However, in cases of unsuccessful treatment, extracorporeal cardiopulmonary resuscitation may additionally provide an important source of organ donors. Therefore, we hypothesized that implementing extracorporeal cardiopulmonary resuscitation service into a high-volume cardiac arrest center's routine would increases organ donors' availability.METHODSOur retrospective observational study analyzed out-of-hospital cardiac arrest patients admitted to the General University Hospital in Prague between 2007 and 2020. The following groups were analyzed regarding the recruitment of donors: before and after extracorporeal cardiopulmonary resuscitation implementation. We assessed the number of donors referred, the number of organs harvested, and the organ's survival.RESULTSWe analyzed the results of 1158 patients after out-of-hospital cardiac arrest. In the conventional approach period, 11 donors were referred, of which seven were accepted. During the extracorporeal cardiopulmonary resuscitation period, the number of donors increased to 80, of whom 42 were accepted. The number of donated organs was 18 and 119 in the respective periods, corresponding to 3.6 vs. 13.2 (p = 0.033) harvested organs per year. One-year survival of transplanted organs was 94.4% vs. 99.2%, and five-year survival was 94.4% vs. 95.9% in relevant periods. Conventional and extracorporeal cardiopulmonary resuscitation did not affect donor organ survival.CONCLUSIONEstablishing a high-volume cardiac arrest centre providing an extracorporeal cardiopulmonary resuscitation service may increase not only the number of prolonged cardiac arrest survivors but also the number of organ donors. In addition, the performances of donated organs were high and comparable between both treatment methods.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob Simmonds,Steven D Zangwill,Bethany Wisotzkey,Ryan Cantor,Hong Zhao,James K Kirklin,Dipankar Gupta
{"title":"Mechanical Circulatory Support Early After Pediatric Heart Transplantation - an analysis from the Pediatric Heart Transplant Society.","authors":"Jacob Simmonds,Steven D Zangwill,Bethany Wisotzkey,Ryan Cantor,Hong Zhao,James K Kirklin,Dipankar Gupta","doi":"10.1016/j.healun.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.003","url":null,"abstract":"BACKGROUNDThe use of early Mechanical Circulatory Support (MCS) following pediatric heart transplantation is not well-published. This paper attempts to uncover the incidence, predisposing factors and outcomes of MCS in a large, international cohort.METHODSThe Pediatric Heart Transplant Society Database (an international, prospective, event-driven database) was retrospectively analyzed for all cases of primary heart transplant over an 11-year period (2010-2020), dividing the cohort based on need for MCS within 30 days of transplantation.RESULTSOf 4321 primary transplants, 249 (5.8%) required MCS (230 ECMO, 19 VAD). In a Cox proportional hazard model, congenital heart disease (p = 0.0002), older donor age (p < 0.0001), and longer ischemic time (p = 0.018) were each related to an increased need for MCS; increasing recipient body surface area (p < 0.0001) and increasing donor left ventricular ejection fraction (p = 0.016) were both correlated with less MCS use. 1-year survival in those requiring MCS was 54.2%, compared with 94.8% in those who did not need MCS (p < 0.0001). Later survival in patients surviving to one year was similar between the groups.CONCLUSIONSMCS is used infrequently following pediatric heart transplant, and is related to donor, recipient and transplant factors. Although mortality is high, those surviving the first year post-transplant have excellent outcomes. Judicious use in those patients who would otherwise perish is therefore justified.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen Chiu,Katherine Bunclark,Paula Appenzeller,Hakim Ghani,Dolores Taboada,Karen Sheares,Mark Toshner,Joanna Pepke-Zaba,John Cannon,Fouad Taghavi,Steven Tsui,Choo Ng,David P Jenkins
{"title":"Impact of Preoperative Body Mass Index on Long-term Survival, Quality of Life, and Functional Outcomes after Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension: Results from the UK National Cohort.","authors":"Stephen Chiu,Katherine Bunclark,Paula Appenzeller,Hakim Ghani,Dolores Taboada,Karen Sheares,Mark Toshner,Joanna Pepke-Zaba,John Cannon,Fouad Taghavi,Steven Tsui,Choo Ng,David P Jenkins","doi":"10.1016/j.healun.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.005","url":null,"abstract":"BACKGROUNDPrevious studies have demonstrated the safety of pulmonary endarterectomy (PEA) in all body mass index (BMI) strata. However, long-term survival and patient-reported quality of life outcome measures by BMI strata remain unknown. We sought to examine the impact of preoperative BMI on long-term survival, quality of life, and functional outcomes for patients undergoing PEA for chronic thromboembolic pulmonary hypertension (CTEPH).METHODSRetrospective review of 2004 patients from the UK National Cohort between 2007 and 2021 undergoing PEA for CTEPH (mPAP>20 mmHg and PVR>160 dynes). Patients were stratified into BMI<20, 20-29, 30-39, 40-49, and 50+. All-cause mortality was the primary outcome measure. Secondary outcome measures were 3-6 month postoperative hemodynamics, 6-minute walk distance (6MWD), New York Heart Association (NYHA) class, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) scores. Kruskal-Wallis, ANOVA, and Kaplan Meier Estimate were used for comparisons.RESULTSPostoperative hemodynamics and 6MWD at 3-6 months were similar across BMI strata. However, patients with BMI 50+ reported the highest incidence of post-operative NYHA III/IV limitation (53.3%, p<0.001) and the highest residual symptom burden by CAMPHOR (p<0.001). Overall 5-year survival was lowest in patients with BMI 50+ (70.2%) and BMI<20 (73.4%), whilst highest in BMI 30-39 (88.2%, p=0.008). 10-year Kaplan-Meier Estimates predicted lowest survival in BMI 50+ and BMI<20.CONCLUSIONPEA remains safe and effective for all patients regardless of BMI. Despite similar hemodynamic outcomes, patients with BMI 50+ are at greatest risk of long-term all-cause mortality and patients with BMI 50+ experience residual symptomatic limitation.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Severe Early Graft Dysfunction Post-Heart Transplantation: Two Clinical Trajectories and Diastolic Perfusion Pressure as a Predictor of Mechanical Circulatory Support.","authors":"Hoong Sern Lim,Sai Bhagra,Marius Berman,Shing Kwok Chun,Colin Chue,Aaron Ranasinghe,Stephen Pettit","doi":"10.1016/j.healun.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.002","url":null,"abstract":"BACKGROUNDSevere early graft dysfunction (EGD) is defined by mechanical circulatory support (MCS) <24 hours of heart transplantation (HT). We classified severe EGD based on timing of post-HT MCS: 'Immediate' intra-operative vs 'Delayed' post-operative MCS (after admission into intensive care unit (ICU) from operating theatre). We hypothesised that (i) risk factors and clinical course differ between 'Immediate' and 'Delayed' MCS; and (ii) diastolic perfusion pressure (DPP=diastolic blood pressure-central venous pressure) and Norepinephrine equivalents (NE=sum of vasopressor doses), as measures of vasoplegia are related to 'Delayed' MCS.METHODSTwo-centre study of 216 consecutive patients who underwent HT. Recipient, donor, vasopressor doses and hemodynamic data at T0 and T6 (on admission and 6 hours after admission into ICU) were collected.RESULTSOf the 216 patients, 67 patients had severe EGD ('Immediate' MCS: n=43, 'Delayed' MCS: n=24). The likelihood of 'immediate' MCS but not 'delayed' MCS increased with increasing warm ischemic and cardiopulmonary bypass times on multinomial regression analysis with 'no MCS' as the referent group. One-year mortality was highest in 'Immediate' MCS vs 'no MCS' and 'delayed' MCS (34.9% vs 3.4% and 8% respectively, P<0.001). Of the patients who had no immediate post-transplant MCS, DPP and NE at T6 were independently associated with subsequent 'delayed' MCS'. Sensitivity and specificity of NE ≥0.2mcg/kg/min for 'Delayed' MCS were 71% and 81%. Sensitivity and specificity of DPP of ≥40mmHg for No MCS were 83% and 74%. The discriminatory value of systemic vascular resistance for 'Delayed' MCS was poor.CONCLUSIONRisk factors and one-year survival differed significantly between 'Immediate' and 'Delayed' post-HT MCS. The latter is related to lower DPP and higher NE, which is consistent with vasoplegia as the dominant pathophysiology.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD.","authors":"Selianne Graf,Manuel Egle,Maria-Nieves Sanz,Adrian Segiser,Alexia Clavier,Maria Arnold,Didier Gsponer,Maris Bartkevics,Alexander Kadner,Matthias Siepe,Peter Vermathen,Sarah Longnus","doi":"10.1016/j.healun.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.healun.2024.08.016","url":null,"abstract":"BACKGROUNDHeart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality.METHODSCirculatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy.RESULTSCirculating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min.CONCLUSIONSIn heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Moraes, M. Heringer, G. Campos, L. Xavier, S. Mangini, F. Bacal
{"title":"Reactivation of Chagas Disease","authors":"S. Moraes, M. Heringer, G. Campos, L. Xavier, S. Mangini, F. Bacal","doi":"10.1016/j.healun.2024.02.1250","DOIUrl":"https://doi.org/10.1016/j.healun.2024.02.1250","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"56 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Kittleson, J. Patel, A. Nikolova, M. White, N. Bhatnagar, A. Kanungo, M. Lee, E. Chow, J. Moriguchi, D. Geft, L. Czer, F. Esmailian, J. Kobashigawa
{"title":"Natural Outcome of Isolated Right Ventricular Dysfunction Immediately After Heart Transplantation","authors":"M. Kittleson, J. Patel, A. Nikolova, M. White, N. Bhatnagar, A. Kanungo, M. Lee, E. Chow, J. Moriguchi, D. Geft, L. Czer, F. Esmailian, J. Kobashigawa","doi":"10.1016/j.healun.2024.02.687","DOIUrl":"https://doi.org/10.1016/j.healun.2024.02.687","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"231 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140762337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}