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Introduction: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA)., Methods: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework., Results: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab., Conclusion: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx)., Methods: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab., Results: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab., Conclusion: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports., Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate., Results: Data were available from 19 centers in North America ( n = 7), South America ( n = 1), and Europe ( n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease ( n = 62), coronary artery disease (CAD) ( n = 16), constrictive pericarditis ( n = 17), aortic pathology ( n = 13), and myxoma ( n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% ( n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively., Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gökler, Aliabadi-Zuckermann, Kaider, Ambardekar, Antretter, Artemiou, Bertolotti, Boeken, Brossa, Copeland, Generosa Crespo-Leiro, Eixeré-Esteve, Epailly, Farag, Hulman, Khush, Masetti, Patel, Ross, Rudež, Silvestry, Suarez, Vest and Zuckermann.)

Cardiac allograft vasculopathy (CAV) after heart transplantation is a fibro-proliferative process affecting coronary arteries of the graft in up to 46.8% of the cases during the first 10 years post-transplantation. It is one of the main causes of graft loss and death. Due to graft denervation, CAV causing ischemia is usually clinically silent until the disease is far advanced. In this study, we compared coronary angiography with intravascular ultrasound (IVUS) for CAV detection. OUTCOMES: A total of 114 patients with HTx who underwent coronary angiography and IVUS between March 2018 and March 2019 were included. Mean follow-up was 87 ± 61 month. Lesions documented by coronary angiography were found in only 27 (24%) of the 114 patients. IVUS revealed ISHLT CAV 0 in 87 patients (76.3%); ISHLT CAV 1 in 15 (13,1%) and ISHLT CAV 2 and CAV 3 in 6 patients (5.2%) each. Among 328 IVUS images, maximum intimal thickness (MIT) >0.5 mm was obtained in 60 vessels (52%) with 24 patients having three-vessel and 19 two-vessel involvement. CONCLUSION: As an adjunct to conventional coronary angiography to detect angiographically silent CAV in heart transplant patients, IVUS is a reliable and safe technique with a low complication rate. Large multicenter studies are necessary to confirm these findings and the potential long-term clinical impact of early detection in clinically and angiographically silent phase., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Supraventricular arrhythmias (SVAs), commonly managed with radiofrequency ablation (RFA), may occur after orthotopic heart transplantation (OHT)., Methods: We retrospectively assessed 514 consecutive patients (pts.) undergoing OHT between January 1990 and July 2016 in a single-center. Patients with SVAs managed with RFA were included. Mechanisms of genesis of SVAs, association with surgical techniques and outcomes, were analyzed., Results: Of 514 pts undergoing OHT, 53% (272 pts.) were managed with bicaval (BC) technique and 47% (242 pts.) with biatrial (BA) technique. Mean follow-up 10 ± 8.4 years. Nine pts. (1.7%) developed SVA requiring RFA. The BC technique was performed in 4 pts., 3 pts. presented cavotricuspid isthmus-dependent atrial flutter (CTI AFL), and 1 pt. double loop AFL. Five pts. were managed with BA technique, 4 pts. presented CTI AFL, and 1 pt. atrial tachycardia (AT). Mean time between OHT and SVA occurrence was 6.6 ± 5.5 years. The procedure was successful in 89% (8 pts.). Arrhythmia recurrence was seen in 3 pts (37%), all with BA technique., Conclusion: Supraventricular arrhythmias in heart transplantation may be associated with the surgical scar. Identifying the mechanism is vital to choose the appropriate treatment with radiofrequency ablation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiogenic shock (CS) has a high mortality rate and often requires advanced therapies such as mechanical circulatory support (MCS) and heart transplantation (HT). Those patients who presented an acute myocardial infarction (AMI) with CS and required support through MCS as bridge to HT were retrospectively analyzed in a single Center. Between January 1997 and June 2020, 524 patients received HT, 203 for ischemic-cardiomyopathy, 103 were in emergency waiting list. Eleven patients met the inclusion criteria (mean age 53 ± 11 years old; men 73%). Five primary angioplasties and 2 emergency myocardial revascularization surgeries were performed. Four patients had coronary anatomy not subject to revascularization. All received inotropic and vasopressor treatment and required intra-aortic balloon pump (IABP). Subsequently, two required support with a left univentricular centrifugal pump (BioMedicus®, Medtronic) and two with peripheral veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (Maquet®, Getinge Group). The median between AMI and HT was 15 days (range 7-21) and the mean age of the donors 28 ± 11 years. All had extensive AMI (necrotic amount 35 ± 5%) with histopathological signs of transmural necrosis and reperfusion injury. The median follow-up was 9 years (range 1-15). None died in hospitalization or during the first year after transplantation. Survival at 5 and 10 years was 73% and 55%. Emergency HT may be the best option for selected patients with acute myocardial infarction and cardiogenic shock refractory to conventional therapy.

Background: Patients with cardiogenic shock may require hemodynamic stabilization with short-term mechanical circulatory support devices (ST-MCS) such as extracorporeal membrane oxygenation (ECMO) and centrifugal pump (CP) as bridge to transplantion (BTT). This study aimed to describe ECMO and CP during BTT and after heart transplant., Methods: A cohort of patients on ECMO or CP as BTT between April 2006 and April 2018 in a single hospital., Results: Thirty-seven consecutive patients with ECMO (n = 14) or CP (n = 23) were included. Acute kidney injury was more prevalent during CP (28.6% vs 69.6%, P = .02). There were no differences in stroke, thrombosis, sepsis, or vasoplegia. Bleeding (0% vs 56.5%, P = .0003) and reoperation (0% vs 47.8%, P = .002) were more frequent in CP group as well as mortality (0 vs 7 [30.4%], P = .03). The remaining 30 patients (81.1%) underwent heart transplantation, without differences in primary graft dysfunction, vasoplegia, reoperation for bleeding, or hospital stay. Mortality was 23.3% at 30 days, similar in both groups, with no further deaths at median follow-up of 44.2 months., Conclusions: In patients with cardiogenic shock, ST-MCS with ECMO or CP as BTT are a lifesaving approach allowing successful transplantation in the majority of cases, with good short- and long-term survival., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Long segment tracheobronchial stenoses are associated with high morbi-mortality rates and difficult treatment. Transplantation hasn't proved to be useful yet. Currently, the successful results achieved in small animal models couldn't be satisfactorily accomplished or extrapolated in large mammals. We aimed to evaluate the viability of orthotopic tracheal autoimplantation in an ovine model., Methods: All animals underwent tracheal transplantation of 4 cm (5-7 rings) of the cervical trachea and were divided randomly in two groups: isolated autoimplantation (Group A/6) and autoimplantation with omental wrapping (Group B/6). Clinical follow up and weekly bronchoscopical examinations were performed. The grafts were macroscopically, histologically, and bacteriologically analyzed., Results: In group A, four animals achieved their planed survival and were sacrificed up to 60 days after transplantation with viable grafts. In group B, only two sheep had successful results. Graft failure with infection, necrosis and severe stenosis was observed in the rest of the animals from both groups. Pseudomonas aeruginose was isolated in all cases. The main complication of the omental pedicle was vascular congestion and peritracheal hemorrhage., Conclusions: Contrary to the data reported to date, we found that tracheal transplantation is viable in a large mammal like the sheep. The main complication observed in this animal model was graft infection. The use of an omental pedicle with the technique applied worsened the grafts survival. The encouraging results obtained in this investigation justify further research in order to manage graft infection, leading us to establish a suitable large animal model for allotransplantation.

Background: Studies on whether surgical lung biopsy (SLB) modifies the treatment of patients with diffuse lung disease are conflicting, and information is limited on whether it alters treatment in solid-organ transplant recipients. Our objective was to determine and compare the rate of treatment change after SLB for diffuse lung disease in patients with and without a history of solid-organ transplantation., Methods: Patients undergoing SLB for diffuse lung disease between March 2004 and March 2009 were identified. A retrospective review was performed., Results: Sixty patients had SLB. Thirty-four patients (57%) had solid-organ transplantation. Twenty of 60 patients (33%) had a change in treatment as a result of the findings of the SLB. No significant differences in the treatment change rate were found between the transplant and nontransplant groups (10 of 34 versus 10 of 26; p = 0.46). Transplant patients were more likely to be on mechanical ventilation at the time of SLB (12 of 34 versus 3 of 26; p = 0.03). Mechanical ventilatory support at the time of SLB was associated with increased postoperative complications (odds ratio, 6.20; 95% confidence interval [CI], 1.70 to 22.66; p = 0.006) and in-hospital mortality (odds ratio, 9.75; 95% CI, 2.54 to 37.38; p = 0.001). Being on mechanical ventilation (hazard ratio, 3.91; 95% CI, 1.40 to 10.93; p = 0.009), a diagnosis of cancer (hazard ratio, 13.20; 95% CI, 2.87 to 60.78; p = 0.001), and a history of solid-organ transplantation (hazard ratio, 5.52; 95% CI, 1.08 to 28.14; p = 0.04) were independent predictors of survival., Conclusions: Surgical lung biopsy changes treatment in one third of patients, with no significant difference between patients without transplantation and solid-organ transplant recipients. Patients who undergo SLB while on mechanical ventilation have a significantly increased risk of postoperative complications and death., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Use of a majority of structural variables (age, sex, height) to estimate oxygen consumption in the calculation of cardiac output (CO) by the Fick principle does not account for changes in physiological conditions. To improve this limitation, oxygen consumption was estimated based on the left ventricular pressure-volume area. A pilot study with 10 patients undergoing right cardiac catheterization showed that this approach was successful to estimate CO (r=0,73, vs. thermodilution measured CO). Further essays changing end-diastolic-volume in the pressure-volume area formula by body weight or body surface area showed that this last yielded the best correlation with the thermodilution measured CO (slope=1, ordinate =0.01 and r=0.93). These preliminary results indicate that use of a formula originated from the pressure-volume-area concept is a good alternative to estimate oxygen consumption for CO calculation.