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1.
Clin Transplant ; 38(7): e15397, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39007406

RÉSUMÉ

BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.


Sujet(s)
Rejet du greffon , Survie du greffon , Transplantation cardiaque , Conservation d'organe , Humains , Transplantation cardiaque/effets indésirables , Mâle , Femelle , Conservation d'organe/méthodes , Adulte d'âge moyen , Études de suivi , Rejet du greffon/étiologie , Rejet du greffon/anatomopathologie , Pronostic , Adulte , Lésion d'ischémie-reperfusion/étiologie , Lésion d'ischémie-reperfusion/anatomopathologie , Cryoconservation/méthodes , Donneurs de tissus/ressources et distribution , Complications postopératoires , Études rétrospectives
2.
Clin Transplant ; 38(7): e15380, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38952201

RÉSUMÉ

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.


Sujet(s)
Anticoagulants , Transplantation cardiaque , Antiagrégants plaquettaires , Humains , Femelle , Mâle , Études rétrospectives , Adulte d'âge moyen , Antiagrégants plaquettaires/usage thérapeutique , Anticoagulants/usage thérapeutique , Études de suivi , Transplantation cardiaque/effets indésirables , Pronostic , Transfusion sanguine , Facteurs de risque , Sujet âgé , Adulte , Dabigatran/usage thérapeutique , Complications postopératoires/prévention et contrôle
3.
Iran J Med Sci ; 49(6): 359-368, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38952641

RÉSUMÉ

Background: Heart transplantation is the preferred treatment for end-stage heart failure. This study investigated the intra-operative risk factors affecting post-transplantation mortality. Methods: This single-center retrospective cohort study examined 239 heart transplant patients over eight years, from 2011-2019, at the oldest dedicated cardiovascular center, Shahid Rajaee Hospital (Tehran, Iran). The primary evaluated clinical outcomes were rejection, readmission, and mortality one month and one year after transplantation. For data analysis, univariate logistic regression analyses were conducted. Results: In this study, 107 patients (43.2%) were adults, and 132 patients (56.8%) were children. Notably, reoperation due to bleeding was a significant predictor of one-month mortality in both children (OR=7.47, P=0.006) and adults (OR=172.12, P<0.001). Moreover, the need for defibrillation significantly increased the risk of one-month mortality in both groups (children: OR=38.00, P<0.001; adults: OR=172.12, P<0.001). Interestingly, readmission had a protective effect against one-month mortality in both children (OR=0.02, P<0.001) and adults (OR=0.004, P<0.001). Regarding one-year mortality, the use of extracorporeal membrane oxygenation (ECMO) was associated with a higher risk in both children (OR=7.64, P=0.001) and adults (OR=12.10, P<0.001). For children, reoperation due to postoperative hemorrhage also increased the risk (OR=5.14, P=0.020), while defibrillation was a significant risk factor in both children and adults (children: OR=22.00, P<0.001; adults: OR=172.12, P<0.001). The median post-surgery survival was 22 months for children and 24 months for adults. Conclusion: There was no correlation between sex and poorer outcomes. Mortality at one month and one year after transplantation was associated with the following risk factors: the use of ECMO, reoperation for bleeding, defibrillation following cross-clamp removal, and Intensive Care Unit (ICU) stay. Readmission, on the other hand, had a weak protective effect.


Sujet(s)
Transplantation cardiaque , Humains , Transplantation cardiaque/statistiques et données numériques , Transplantation cardiaque/méthodes , Transplantation cardiaque/mortalité , Transplantation cardiaque/effets indésirables , Transplantation cardiaque/tendances , Mâle , Femelle , Facteurs de risque , Études rétrospectives , Iran/épidémiologie , Enfant , Adulte , Adulte d'âge moyen , Réadmission du patient/statistiques et données numériques , Adolescent , Enfant d'âge préscolaire , Réintervention/statistiques et données numériques , Réintervention/mortalité , Réintervention/méthodes , Jeune adulte , Complications postopératoires/mortalité , Défaillance cardiaque/mortalité , Défaillance cardiaque/chirurgie
4.
Clin Transplant ; 38(7): e15385, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38973775

RÉSUMÉ

INTRODUCTION: Symptom distress after heart transplantation (HTx) is a significant problem causing uncertainty, low self-efficacy, and psychological distress. Few studies have addressed self-reported symptoms. The aim was to explore self-reported symptom distress from time on the waiting list to 5 years after HTx and its association with self-reported psychological well-being, chronic pain, and fatigue in order to identify possible predictors of psychological or transplant specific well-being. METHODS: This multicenter, longitudinal cohort study includes 48 heart recipients (HTRs), 12 women, and 36 men, with a median age of 57 years followed from pretransplant to 5 years post-transplant. Symptom distress was explored by means of four instruments measuring psychological general wellbeing, transplant specific wellbeing, pain, and fatigue. RESULTS: Transplant specific well-being for the whole improved in a stepwise manner during the first 5 years compared to pretransplant. Heart transplant recipients with poor psychological wellbeing were significantly more burdened by symptom distress, in particular sleep problems and fatigue, for up to 5 years after HTx, and their transplant-specific well-being never improved compared to baseline. The prevalence of pain varied from 40% to 60% and explained a significant proportion of the variance in transplant-specific well-being, while psychological general well-being was mainly predicted by overall symptom distress. CONCLUSION: The presence of distressing symptoms explains a significant proportion of poor psychological wellbeing both among HTRs reporting chronic pain and those without pain.


Sujet(s)
Transplantation cardiaque , Qualité de vie , Humains , Transplantation cardiaque/psychologie , Transplantation cardiaque/effets indésirables , Mâle , Femelle , Adulte d'âge moyen , Études de suivi , Études longitudinales , Pronostic , Fatigue/étiologie , Adulte , Complications postopératoires/psychologie , Complications postopératoires/étiologie , Sujet âgé , Stress psychologique/étiologie , Détresse psychologique , Facteurs de risque
5.
Exp Clin Transplant ; 22(5): 386-391, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38970282

RÉSUMÉ

OBJECTIVES: Heart transplant is the most effective treatment in patients with advanced heart failure who are refractory to medical treatment. The brain death interval and type of inotrope We assessed the effects of these parameters on heart transplant outcomes. MATERIALS AND METHODS: In this follow-up study, we followed heart transplant recipients for 1 year to study patient survival, ejection fraction, adverse events, and organ rejection. We evaluated follow-up results on time from brainstem death test to the cross-clamp placement, as well as the type of inotrope used. RESULTS: Our study enrolled 54 heart transplant candidates. The inotrope dose was 3.66 ± 0.99 µg/kg/min, and the most used inotrope, with 28 cases (51.9%), was related to dopamine. Six cases (11.1%) of death and 1 case of infection after transplant were observed in recipients. The average ejection fraction of transplanted hearts before transplant, instantly at time of transplant, and 1 month, 6 months, and 1 year after transplant was 54.9 ± 0.68, 52.9 ± 10.4, 51.9 ± 10.7, 50.1 ± 10.9, and 46.8 ± 17, respectively; this decreasing trend over time was significant (P =.001). Furthermore, ejection fraction changes following transplant did not differ significantly in transplanted hearts regarding brain death interval and type of inotrope used. CONCLUSIONS: Our study revealed that cardiac output of a transplanted heart may decrease over time and the time elapsed from brain death, and both dopamine and norepinephrine could have negligible effects on cardiac function.


Sujet(s)
Mort cérébrale , Cardiotoniques , Défaillance cardiaque , Transplantation cardiaque , Humains , Transplantation cardiaque/effets indésirables , Transplantation cardiaque/mortalité , Facteurs temps , Mâle , Femelle , Adulte d'âge moyen , Résultat thérapeutique , Adulte , Défaillance cardiaque/physiopathologie , Défaillance cardiaque/chirurgie , Défaillance cardiaque/diagnostic , Défaillance cardiaque/mortalité , Cardiotoniques/usage thérapeutique , Cardiotoniques/effets indésirables , Études de suivi , Facteurs de risque , Débit systolique/effets des médicaments et des substances chimiques , Fonction ventriculaire gauche/effets des médicaments et des substances chimiques , Dopamine , Rejet du greffon/prévention et contrôle , Rejet du greffon/immunologie
6.
Exp Clin Transplant ; 22(5): 406-408, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38970287

RÉSUMÉ

Vasoplegia describes a constellation of low vascular resistance and normal cardiac output. Vasoplegia is common after cardiac surgery in general and in heart transplant recipients more specifically and occurs in over one-half of all heart transplant recipients with a varying degree of severity. The pathophysiology of vasoplegia is multifactorial and associated with a cascade of inflammatory mediators. Routine treatment of vasoplegia is based on medical vasopressor therapy, but in severe cases this may be insufficient to maintain adequate blood pressure and does not address the underlying pathophysiology. We report a case of severe vasoplegic shock in a heart transplant recipient who was successfully managed with a multimodal therapy combination of methylene blue, immunoglobulins enriched with immunoglobulin M, cytokine adsorption, and broad-spectrum antibiotics. This represents a promising therapeutic approach for heart transplant patients with vasoplegia.


Sujet(s)
Transplantation cardiaque , Bleu de méthylène , Vasoplégie , Humains , Transplantation cardiaque/effets indésirables , Vasoplégie/traitement médicamenteux , Vasoplégie/étiologie , Vasoplégie/physiopathologie , Vasoplégie/diagnostic , Résultat thérapeutique , Association thérapeutique , Indice de gravité de la maladie , Antibactériens/usage thérapeutique , Mâle , Cytokines , Adulte d'âge moyen , Choc/physiopathologie , Choc/étiologie , Choc/diagnostic , Choc/thérapie , Choc/traitement médicamenteux
9.
Nat Commun ; 15(1): 4309, 2024 Jun 03.
Article de Anglais | MEDLINE | ID: mdl-38830846

RÉSUMÉ

The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation.


Sujet(s)
Abatacept , Sérum antilymphocyte , Rejet du greffon , Survie du greffon , Transplantation cardiaque , Interleukine-6 , Lymphocytes T régulateurs , Animaux , Mâle , Souris , Abatacept/pharmacologie , Abatacept/usage thérapeutique , Allogreffes/immunologie , Sérum antilymphocyte/pharmacologie , Sérum antilymphocyte/usage thérapeutique , Rejet du greffon/immunologie , Rejet du greffon/prévention et contrôle , Survie du greffon/effets des médicaments et des substances chimiques , Survie du greffon/immunologie , Transplantation cardiaque/effets indésirables , Immunosuppresseurs/pharmacologie , Interleukine-10/métabolisme , Interleukine-10/immunologie , Interleukine-6/métabolisme , Déplétion lymphocytaire , Souris de lignée BALB C , Souris de lignée C57BL , Lymphocytes T régulateurs/immunologie , Lymphocytes T régulateurs/effets des médicaments et des substances chimiques
10.
J Surg Res ; 300: 325-335, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38838430

RÉSUMÉ

INTRODUCTION: Higher donor sequence numbers (DSNs) might spark provider concern about poor donor quality. We evaluated characteristics of high-DSN offers used for transplant and compared outcomes of high- and low-DSN transplants. MATERIALS AND METHODS: Adult isolated heart transplants between January 1, 2015, and December 31, 2022, were identified from the organ procurement and transplantation network database and stratified into high (≥42) and low (<42) DSN. Postoperative outcomes, including predischarge complications, hospital length of stay, and survival at 1 and 3 y, were evaluated using multivariable regressions. RESULTS: A total of 21,217 recipients met the inclusion criteria, with 2131 (10.0%) classified as high-DSN. Donor factors associated with greater odds of high-DSN at acceptance included older age, higher creatinine, diabetes, hypertension, and lower left ventricular ejection fraction. Recipients accepting high-DSN offers were older and more likely to be female, of blood type O, and have lower status at transplant. High- and low-DSN transplants had similar likelihood of stroke (3.2% versus 3.5%; P = 0.97), dialysis (12.3% versus 13.5%; P = 0.12), pacemaker implant (2.3% versus 2.1%; P = 0.64), had similar lengths of stay (16 [12-24] versus 16 [12-25] days, P = 0.38), and survival at 1 (91.6% versus 91.6%; aHR 0.85 [0.72-1.02], P = 0.08) and 3 y (84.2% versus 85.1%; aHR 0.91 [0.79-1.05], P = 0.21) post-transplant. CONCLUSIONS: High-DSN (≥42) was not an independent risk factor for post-transplant mortality and should not be the sole deterrent to acceptance. Accepting high-DSN organs may increase access to transplantation for lower-status candidates.


Sujet(s)
Transplantation cardiaque , Donneurs de tissus , Transplantation cardiaque/effets indésirables , Transplantation cardiaque/statistiques et données numériques , Humains , Mâle , Femelle , Adulte d'âge moyen , Adulte , Donneurs de tissus/statistiques et données numériques , Sujet âgé , Études rétrospectives , Complications postopératoires/épidémiologie , Complications postopératoires/étiologie , Acquisition d'organes et de tissus/statistiques et données numériques , Résultat thérapeutique , Durée du séjour/statistiques et données numériques
12.
PLoS One ; 19(6): e0304588, 2024.
Article de Anglais | MEDLINE | ID: mdl-38829911

RÉSUMÉ

Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.


Sujet(s)
Modèles animaux de maladie humaine , Rejet du greffon , Transplantation cardiaque , Imagerie par résonance magnétique , Transplantation hétérotopique , Transplantation cardiaque/effets indésirables , Animaux , Rejet du greffon/imagerie diagnostique , Suidae , Imagerie par résonance magnétique/méthodes , Maladie aigüe , Myocarde/anatomopathologie
13.
J Cardiothorac Surg ; 19(1): 313, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38824545

RÉSUMÉ

Primary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the initial 24 h following heart transplantation, in the absence of a discernible secondary cause. Given its intricate nature, definitive definition and diagnosis of PGD continues to pose a challenge. The pathophysiology of PGD encompasses numerous underlying mechanisms, some of which remain to be elucidated, including factors like myocardial damage, the release of proinflammatory mediators, and the occurrence of ischemia-reperfusion injury. The dynamic characteristics of both donors and recipients, coupled with the inclination towards marginal lists containing more risk factors, together contribute to the increased incidence of PGD. The augmentation of therapeutic strategies involving mechanical circulatory support accelerates myocardial recovery, thereby significantly contributing to survival. Nonetheless, a universally accepted treatment algorithm for the swift management of this clinical condition, which necessitates immediate intervention upon diagnosis, remains absent. This paper aims to review the existing literature and shed light on how diagnosis, pathophysiology, risk factors, treatment, and perioperative management affect the outcome of PGD.


Sujet(s)
Transplantation cardiaque , Dysfonction primaire du greffon , Humains , Transplantation cardiaque/effets indésirables , Dysfonction primaire du greffon/diagnostic , Dysfonction primaire du greffon/étiologie , Dysfonction primaire du greffon/physiopathologie , Facteurs de risque
14.
Cardiovasc Diabetol ; 23(1): 216, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907259

RÉSUMÉ

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.


Sujet(s)
Circulation coronarienne , Diabète de type 2 , Transplantation cardiaque , Imagerie de perfusion myocardique , Valeur prédictive des tests , Dysfonction ventriculaire gauche , Fonction ventriculaire gauche , Humains , Transplantation cardiaque/effets indésirables , Mâle , Adulte d'âge moyen , Femelle , Diabète de type 2/physiopathologie , Diabète de type 2/complications , Diabète de type 2/diagnostic , Imagerie de perfusion myocardique/méthodes , Dysfonction ventriculaire gauche/physiopathologie , Dysfonction ventriculaire gauche/imagerie diagnostique , Dysfonction ventriculaire gauche/étiologie , Résultat thérapeutique , Adulte , IRM dynamique , Facteurs de risque , Sujet âgé , Études cas-témoins , Facteurs temps , Phénomènes biomécaniques , Marqueurs biologiques/sang , Contraction myocardique
15.
Front Immunol ; 15: 1418665, 2024.
Article de Anglais | MEDLINE | ID: mdl-38911849

RÉSUMÉ

Introduction: Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management. Case presentation: A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation. Discussion: EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition. Conclusion: Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.


Sujet(s)
Transplantation cardiaque , Syndrome hyperéosinophilique , Myocardite , Humains , Syndrome hyperéosinophilique/diagnostic , Syndrome hyperéosinophilique/complications , Syndrome hyperéosinophilique/traitement médicamenteux , Myocardite/étiologie , Myocardite/diagnostic , Myocardite/thérapie , Femelle , Adulte d'âge moyen , Transplantation cardiaque/effets indésirables , Défaillance cardiaque/étiologie , Éosinophilie/étiologie , Éosinophilie/diagnostic
16.
Nat Commun ; 15(1): 3664, 2024 Apr 30.
Article de Anglais | MEDLINE | ID: mdl-38693123

RÉSUMÉ

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). In the second step, talimogene laherparepvec (T-VEC) injection further enhances effector function by switching CD4 and CD8 cells from central memory to effector memory profiles, enhancing Th1 responses, and boosting cytotoxic and proliferative activities. In addition, cytokine release (IL-6, IL-18, sCD25, CCL-2, CCL-4) is enhanced and the frequency of circulating regulatory T cells is increased. Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.


Sujet(s)
Carcinome épidermoïde , Rejet du greffon , Transplantation cardiaque , Herpèsvirus humain de type 1 , Inhibiteurs de mTOR , Transplantation cardiaque/effets indésirables , Humains , Mâle , Rejet du greffon/prévention et contrôle , Rejet du greffon/immunologie , Carcinome épidermoïde/immunologie , Carcinome épidermoïde/traitement médicamenteux , Inhibiteurs de mTOR/pharmacologie , Inhibiteurs de mTOR/usage thérapeutique , Produits biologiques/pharmacologie , Produits biologiques/usage thérapeutique , Tumeurs cutanées/immunologie , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/thérapie , Tumeurs cutanées/traitement médicamenteux , Adulte d'âge moyen , Évérolimus/pharmacologie , Évérolimus/usage thérapeutique , Lymphocytes T/immunologie , Lymphocytes T/effets des médicaments et des substances chimiques , Sérine-thréonine kinases TOR/métabolisme , Sérine-thréonine kinases TOR/antagonistes et inhibiteurs
17.
Exp Clin Transplant ; 22(4): 294-299, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38742320

RÉSUMÉ

OBJECTIVES: Bronchiectasis is characterized by abnormal, persistent, and irreversible enlargement of the bronchi. Many etiological factors have been described, but there are limited data on the development of bronchiectasis after organ transplantation. Our study is the first to study evaluate the frequency of bronchiectasis in heart and liver transplants as well as kidney transplants. Our aim is to analyze the frequency of bronchiectasis development after solid-organ transplant and the characteristics of the cases and to evaluate potential relationships. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent solid-organ transplant at the Baskent University Faculty of Medicine Hospital through the hospital electronic information system. Demographic, clinical, and laboratory data and thoracic computed tomography scans were evaluated. RESULTS: The study included 468 patients (151 females/317 males). Kidney transplant was performed in 61.5% (n = 207), heart transplant in 20.3% (n = 95), and liver transplant in 18.2% (n = 85) of patients. Development of bronchiectasis was detected in only 13 patients (2.7%). We determined a 13.64-fold risk of developing bronchiectasis in patients with chronic obstructive pulmonary disease and 10.08-fold risk in patients with pneumonia by multivariate regression analyzes, in which all possible risk factors for the development of bronchiectasis after transplant were evaluated. CONCLUSIONS: The pathophysiology of transplantassociated bronchiectasis has not yet been clarified. Underlying diseases, recurrent pulmonary infections, and potential effects from immunosuppressive drugs may contribute to the pathogenesis of bronchiectasis. Further prospective studies are needed to include long-term health outcomes in transplant patients with and without bronchiectasis.


Sujet(s)
Dilatation des bronches , Transplantation cardiaque , Transplantation hépatique , Humains , Dilatation des bronches/épidémiologie , Dilatation des bronches/étiologie , Dilatation des bronches/diagnostic , Dilatation des bronches/imagerie diagnostique , Études rétrospectives , Mâle , Femelle , Facteurs de risque , Adulte d'âge moyen , Adulte , Résultat thérapeutique , Transplantation hépatique/effets indésirables , Turquie/épidémiologie , Transplantation cardiaque/effets indésirables , Transplantation rénale/effets indésirables , Facteurs temps , Appréciation des risques , Sujet âgé , Transplantation d'organe/effets indésirables , Jeune adulte , Hôpitaux universitaires , Broncho-pneumopathie chronique obstructive/diagnostic , Broncho-pneumopathie chronique obstructive/épidémiologie
18.
Transplant Proc ; 56(4): 767-772, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38744588

RÉSUMÉ

OBJECTIVE: To evaluate the impact of heart donors and recipients parameters on the outcomes after orthotopic heart transplantation (OHT). METHODOLOGY: Two hundred fifteen patients who underwent OHT from 2020 to 2023 were analyzed. RESULTS: Average donors age 36.3 (±13.1) years, 74 women (34.42%), BMI 25.3 (±4.99), Na+ concentration 153.7 (±11.8) mmol/L. Mean intraventricular septum thickness 10.0 (±2.2) mm, left ventricular end-diastolic diameter 44.3 (±6) mm, ejection fraction 60.3 (±7.92) %. Median procalcitonin was 0.6 ng/mL. Levonor was used in 75.8%, Empressin in 4.2%, Dopamine in 5.1%, Dobutamine in 3.7%, and Adrenaline in 3.7% of donors. The most common cause of death: intracranial injury (34.42%). Cardiopulmonary resuscitation occurred in 34%, alcoholism in 20.9%, nicotinism in 16.3%, and drug addiction in 7.4% of donors. Mean aortic cross-clamping time was 200.3 (±48.8) minutes. Intra-aortic balloon pump (IABP) after OHT required 6.1%, extra corporeal membrane oxygenation (ECMO) 6.1%, and renal dialysis 36% of recipients. The 1-year mortality rate was 19.1%. Death after OHT correlated with: longer aortic cross-clamping time (207.6 vs 198.59 minutes, P = .292), longer extracorporeal circulation time (196.3 vs 186.47 minutes, P = .335), lower Empressin dose (median 0.01 vs 0.02 j.m/min, P = .03) in donors, longer postoperative mechanical ventilation (mean 101.46 vs 23.09 hours, P = .001), more frequent dialysis, IABP or ECMO (P = .001) and older age of the recipient (51.2 vs 44.8 years, P = .014). Previous cardiac surgery or any surgical intervention after transplantation significantly influenced mortality. The remaining donor factors had no impact on the OHT result. CONCLUSIONS: Identification of risk factors in the donor and recipient may improve treatment outcomes after OHT.


Sujet(s)
Transplantation cardiaque , Donneurs de tissus , Humains , Femelle , Adulte , Transplantation cardiaque/effets indésirables , Transplantation cardiaque/mortalité , Mâle , Adulte d'âge moyen , Résultat thérapeutique , Jeune adulte , Études rétrospectives
19.
Transplant Proc ; 56(4): 851-853, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38697907

RÉSUMÉ

BACKGROUND: Bradyarrhythmias, requiring pacemaker (PM) implantation, are common complications following orthotopic heart transplantation (HTx). Currently used heart transplantation methods are primarily the bicaval technique and the total heart transplantation technique. The aim of the study was to assess the incidence and risk factors, including donor parameters, of conduction disorders requiring pacing after HTx. METHODS: A population of 111 (52 ± 13 years, 91 (82%) men) heart recipients was divided into a group requiring PM implantation post-HTx and a group not requiring PM. We compared groups in terms of donor parameters, time of graft ischemia, transport and transplantation, and surgical techniques as the potential risk factors for significant bradyarrhythmias. RESULTS: Ten of 111 patients with HTx (9%) required PM implantation. The indication in 7 cases was sinus node dysfunction (SND), in 3 patients it was complete atrioventricular block (AV-block). In the PM group, the age of 48 ± 6 vs 40 ± 11 years (P = .0227) and the body mass index (BMI) 28 ± 3 vs 26 ± 4 kg/m2 (P = .0297) of the donor were significantly higher. There was no influence of organ transport time, ischemia time, and transplantation time. All patients requiring PM implantation were transplanted using the bicaval anastomosis: 10 (100%) vs 71 (70%) in the group not requiring PM (P = .044). CONCLUSIONS: The need for PM implantation post-HTx despite using new techniques is still common, especially in the group operated with the bicaval method. In addition, higher donor's age and BMI are risk factors of PM implantation, what is of importance as qualification criteria of donor hearts have been gradually extended.


Sujet(s)
Transplantation cardiaque , Pacemaker , Humains , Transplantation cardiaque/effets indésirables , Mâle , Facteurs de risque , Femelle , Adulte d'âge moyen , Adulte , Incidence , Bradycardie/épidémiologie , Bradycardie/étiologie , Études rétrospectives , Donneurs de tissus
20.
Am J Physiol Heart Circ Physiol ; 327(1): H131-H137, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38700470

RÉSUMÉ

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m2 (P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg-1 (P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.


Sujet(s)
Transplantation cardiaque , Hémodynamique , Isoprénaline , Artère pulmonaire , Dysfonction ventriculaire droite , Fonction ventriculaire droite , Humains , Isoprénaline/pharmacologie , Transplantation cardiaque/effets indésirables , Adulte d'âge moyen , Mâle , Artère pulmonaire/physiopathologie , Artère pulmonaire/effets des médicaments et des substances chimiques , Femelle , Fonction ventriculaire droite/effets des médicaments et des substances chimiques , Études rétrospectives , Adulte , Hémodynamique/effets des médicaments et des substances chimiques , Sujet âgé , Dysfonction ventriculaire droite/physiopathologie , Dysfonction ventriculaire droite/étiologie , Défaillance cardiaque/physiopathologie , Défaillance cardiaque/traitement médicamenteux , Dobutamine/pharmacologie , Résultat thérapeutique , Rythme cardiaque/effets des médicaments et des substances chimiques , Récupération fonctionnelle , Cardiotoniques/pharmacologie
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