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1.
Nat Commun ; 15(1): 3664, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38693123

RESUMEN

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.


Asunto(s)
Carcinoma de Células Escamosas , Rechazo de Injerto , Trasplante de Corazón , Herpesvirus Humano 1 , Inhibidores mTOR , Trasplante de Corazón/efectos adversos , Humanos , Masculino , Rechazo de Injerto/prevención & control , Rechazo de Injerto/inmunología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/tratamiento farmacológico , Inhibidores mTOR/farmacología , Inhibidores mTOR/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/tratamiento farmacológico , Persona de Mediana Edad , Everolimus/farmacología , Everolimus/uso terapéutico , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores
2.
Exp Clin Transplant ; 22(4): 294-299, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742320

RESUMEN

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.


Asunto(s)
Bronquiectasia , Trasplante de Corazón , Trasplante de Hígado , Humanos , Bronquiectasia/epidemiología , Bronquiectasia/etiología , Bronquiectasia/diagnóstico , Bronquiectasia/diagnóstico por imagen , Estudios Retrospectivos , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Trasplante de Hígado/efectos adversos , Turquía/epidemiología , Trasplante de Corazón/efectos adversos , Trasplante de Riñón/efectos adversos , Factores de Tiempo , Medición de Riesgo , Anciano , Trasplante de Órganos/efectos adversos , Adulto Joven , Hospitales Universitarios , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
3.
Clin Transplant ; 38(5): e15337, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38762786

RESUMEN

OBJECTIVE: This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. METHODS: Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. RESULTS: Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002-1.115), gender (OR = .200, 95% CI .044-.919), education level (OR = .728, 95% CI .600-.883), LVEF (OR = .891, 95% CI .820-.969), and history of diabetes (OR = 7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05). CONCLUSION: The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.


Asunto(s)
Disfunción Cognitiva , Trasplante de Corazón , Humanos , Masculino , Femenino , Trasplante de Corazón/efectos adversos , Persona de Mediana Edad , Factores de Riesgo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Estudios de Seguimiento , Pronóstico , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Incidencia , Estudios Retrospectivos , Pruebas Neuropsicológicas
5.
Sci Adv ; 10(20): eadk6178, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38748794

RESUMEN

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.


Asunto(s)
Aloinjertos , Biomarcadores , Rechazo de Injerto , Animales , Rechazo de Injerto/inmunología , Ratones , Trasplante de Piel/efectos adversos , Trasplante de Corazón/efectos adversos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Tejido Subcutáneo/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/inmunología , Linfocitos T/metabolismo
6.
Clin Transplant ; 38(4): e15307, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38567897

RESUMEN

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.


Asunto(s)
Trasplante de Corazón , Neoplasias , Humanos , Basiliximab/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunosupresores/farmacología , Anticuerpos Monoclonales/uso terapéutico , Estudios Retrospectivos , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Trasplante de Corazón/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico
7.
Medicine (Baltimore) ; 103(16): e37841, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38640302

RESUMEN

BACKGROUND: While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION: A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION: This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.


Asunto(s)
Trasplante de Corazón , Neoplasias Gástricas , Masculino , Humanos , Anciano , Neoplasias Gástricas/cirugía , Recurrencia Local de Neoplasia , Trasplante de Corazón/efectos adversos , Ecocardiografía , Quimioterapia Adyuvante , Gastrectomía/métodos
8.
Circ Cardiovasc Imaging ; 17(4): e016415, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38563143

RESUMEN

BACKGROUND: In heart transplant recipients, right ventricular (RV) dysfunction may occur for a variety of reasons. Whether RV dysfunction in the stable phase after heart transplantation is associated with long-term adverse outcomes is unknown. We aimed to determine the long-term prognostic significance of RV dysfunction identified on cardiovascular magnetic resonance imaging (CMR) at least 1 year after heart transplantation. METHODS: In consecutive heart transplant recipients who underwent CMR for surveillance, we assessed 2 CMR measures of RV function: RV ejection fraction and RV global longitudinal strain (RVGLS). We investigated associations between RV dysfunction and a composite end point of death or major adverse cardiac events, including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization. RESULTS: A total of 257 heart transplant recipients (median age, 59 years; 75% men) who had CMR at a median of 4.3 years after heart transplantation were included. Over a median follow-up of 4.4 years after the CMR, 108 recipients experienced death or major adverse cardiac events. In a multivariable Cox regression analysis adjusted for age, time since transplantation, indication for transplantation, cardiac allograft vasculopathy, history of rejection, and CMR covariates, RV ejection fraction was not associated with the composite end point, but RVGLS was independently associated with the composite end point with a hazard ratio of 1.08 per 1% worsening in RVGLS ([95% CI, 1.00-1.17]; P=0.046). RVGLS provided incremental prognostic value over other variables in multivariable analyses. The association was replicated in subgroups of recipients with normal RV ejection fraction and recipients with late gadolinium enhancement imaging. A similar association was seen with a composite end point of cardiovascular death or major adverse cardiac events. CONCLUSIONS: CMR feature tracking-derived RVGLS assessed at least 1 year after heart transplantation was independently associated with the long-term risk of death or major adverse cardiac events. Future studies should investigate its role in guiding clinical decision-making in heart transplant recipients.


Asunto(s)
Trasplante de Corazón , Infarto del Miocardio , Masculino , Humanos , Persona de Mediana Edad , Femenino , Imagen por Resonancia Cinemagnética , Función Ventricular Derecha , Medios de Contraste , Factores de Riesgo , Valor Predictivo de las Pruebas , Gadolinio , Imagen por Resonancia Magnética , Volumen Sistólico , Trasplante de Corazón/efectos adversos , Pronóstico , Función Ventricular Izquierda
9.
Transpl Int ; 37: 11878, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644935

RESUMEN

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.


Asunto(s)
Corticoesteroides , Everolimus , Rechazo de Injerto , Trasplante de Corazón , Inmunosupresores , Sistema de Registros , Humanos , Everolimus/administración & dosificación , Everolimus/uso terapéutico , Trasplante de Corazón/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , República de Corea/epidemiología , Rechazo de Injerto/prevención & control , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Resultado del Tratamiento , Supervivencia de Injerto , Estudios Retrospectivos
11.
Int J Mol Sci ; 25(8)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38674016

RESUMEN

Organ transplantation is associated with various forms of programmed cell death which can accelerate transplant injury and rejection. Targeting cell death in donor organs may represent a novel strategy for preventing allograft injury. We have previously demonstrated that necroptosis plays a key role in promoting transplant injury. Recently, we have found that mitochondria function is linked to necroptosis. However, it remains unknown how necroptosis signaling pathways regulate mitochondrial function during necroptosis. In this study, we investigated the receptor-interacting protein kinase 3 (RIPK3) mediated mitochondrial dysfunction and necroptosis. We demonstrate that the calmodulin-dependent protein kinase (CaMK) family members CaMK1, 2, and 4 form a complex with RIPK3 in mouse cardiac endothelial cells, to promote trans-phosphorylation during necroptosis. CaMK1 and 4 directly activated the dynamin-related protein-1 (Drp1), while CaMK2 indirectly activated Drp1 via the phosphoglycerate mutase 5 (PGAM5). The inhibition of CaMKs restored mitochondrial function and effectively prevented endothelial cell death. CaMKs inhibition inhibited activation of CaMKs and Drp1, and cell death and heart tissue injury (n = 6/group, p < 0.01) in a murine model of cardiac transplantation. Importantly, the inhibition of CaMKs greatly prolonged heart graft survival (n = 8/group, p < 0.01). In conclusion, CaMK family members orchestrate cell death in two different pathways and may be potential therapeutic targets in preventing cell death and transplant injury.


Asunto(s)
Dinaminas , Rechazo de Injerto , Trasplante de Corazón , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Animales , Ratones , Rechazo de Injerto/metabolismo , Rechazo de Injerto/patología , Trasplante de Corazón/efectos adversos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Dinaminas/metabolismo , Dinaminas/genética , Mitocondrias/metabolismo , Células Endoteliales/metabolismo , Masculino , Ratones Endogámicos C57BL , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosforilación , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Transducción de Señal
12.
Clin Transplant ; 38(5): e15327, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38686437

RESUMEN

INTRODUCTION: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). METHODS: In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. RESULTS: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. CONCLUSION: This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.


Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Corazón , Humanos , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/etiología , Trasplante de Corazón/efectos adversos , Masculino , Estudios Retrospectivos , Antivirales/uso terapéutico , Femenino , Persona de Mediana Edad , Estudios de Seguimiento , Citomegalovirus/aislamiento & purificación , Adulto , Anciano , Pronóstico , Acetatos/uso terapéutico , Quinazolinas/uso terapéutico , Receptores de Trasplantes , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología
13.
Commun Biol ; 7(1): 488, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649462

RESUMEN

Antibody responses, involving B cells, CD4 + T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.


Asunto(s)
Linfocitos B , Disulfiram , Activación de Macrófagos , Pirimidinas , Animales , Disulfiram/farmacología , Ratones , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Activación de Macrófagos/efectos de los fármacos , Pirimidinas/farmacología , Ratones Endogámicos C57BL , Trasplante de Corazón/efectos adversos , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Formación de Anticuerpos/efectos de los fármacos , Rechazo de Injerto/prevención & control , Rechazo de Injerto/inmunología , Ratones Endogámicos BALB C
14.
Clin Transplant ; 38(3): e15275, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38477134

RESUMEN

BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.


Asunto(s)
Enfermedad de la Arteria Coronaria , Trasplante de Corazón , Placa Aterosclerótica , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Enfermedad de la Arteria Coronaria/etiología , Estudios Prospectivos , Tomografía de Coherencia Óptica/efectos adversos , Tomografía de Coherencia Óptica/métodos , Aloinjertos/patología , Placa Aterosclerótica/complicaciones , Trasplante de Corazón/efectos adversos , Angiografía Coronaria
15.
Clin Transplant ; 38(3): e15281, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38504577

RESUMEN

BACKGROUND: We aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality. METHODS: The study population comprises 193 consecutive long-term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow-up or right censuring on the 30th of June 2023. RESULTS: DSAs were detected in 50 patients using a cut-off at MFI ≥1000 and 45 patients using a cut-off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0-14.4]. DSA positive patients had poorer graft function and higher values of NT-proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow-up of five years [4.7-5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6-2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5-4.8) CONCLUSIONS: Routine screening reveals DSA in approximately 25% of long-term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.


Asunto(s)
Rechazo de Injerto , Trasplante de Corazón , Humanos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Anticuerpos , Trasplante de Corazón/efectos adversos , Donantes de Tejidos , Toma de Decisiones Clínicas , Antígenos HLA , Isoanticuerpos , Estudios Retrospectivos
16.
Clin Transplant ; 38(4): e15294, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38545881

RESUMEN

BACKGROUND: Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). METHODS: We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS: Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20% versus 28.8% at 2 years, and 33.3% versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p = 0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p = 0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. CONCLUSION: Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.


Asunto(s)
Trasplante de Corazón , Hepatitis C , Humanos , Masculino , Persona de Mediana Edad , Femenino , Donantes de Tejidos , Estudios Retrospectivos , Trasplante de Corazón/efectos adversos , Viremia/epidemiología , Viremia/etiología , Estudios de Seguimiento , Hepatitis C/etiología , Hepacivirus , Aloinjertos , Receptores de Trasplantes
17.
Physiol Res ; 73(1): 9-25, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466001

RESUMEN

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.


Asunto(s)
Trasplante de Corazón , Corazón , Femenino , Masculino , Animales , Ratas , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/métodos , Ventrículos Cardíacos/patología , Atrofia/patología , Hormonas Esteroides Gonadales , Miocardio/patología
18.
Am J Case Rep ; 25: e942381, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38431769

RESUMEN

BACKGROUND Idiopathic giant cell myocarditis (IGCM) is an uncommon and frequently fatal type of myocarditis. It primarily affects young individuals and has the potential to result in heart failure and life-threatening arrhythmias. IGCM seems to be dependent on activation of CD4-positive T lymphocytes and can show improvement with treatment aimed at reducing T-cell function. We present a case of a 65-year-old patient who presented with features of acute heart failure refractory to guideline-directed medical therapy (GDMT), due to IGCM. A review of the natural history and treatment of IGCM is also presented. CASE REPORT A 65-year-old woman with multiple comorbidities was admitted to our hospital for ventricular tachycardia in the setting of progressive non-ischemic heart failure, unresponsive to GDMT. This led to further investigation, including an endomyocardial biopsy, which revealed inflammatory infiltration, with multinucleated giant cells and lymphocytes in the absence of granuloma formation, prompting a diagnosis of IGCM. An implantable cardioverter-defibrillator (ICD) was placed for secondary prevention of sudden cardiac death and the patient was initiated on combined immunosuppressive therapy. Owing to numerous comorbidities, she was determined to be unsuitable for a heart transplant. Unfortunately, she eventually died from complications secondary to the disease. CONCLUSIONS IGCM remains a challenging clinical diagnosis with a poor long-term outcome without heart transplantation. This case highlights the importance of considering atypical causes of heart failure in patients who do not respond to conventional therapies. Early recognition and appropriate management, involving medical and interventional approaches, are crucial in improving outcomes for patients with IGCM.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Miocarditis , Femenino , Humanos , Anciano , Miocarditis/diagnóstico , Miocarditis/terapia , Miocarditis/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/efectos adversos , Arritmias Cardíacas/etiología , Células Gigantes/patología
19.
Arq Bras Cardiol ; 121(1): e20230537, 2024.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-38511808

RESUMEN

This case report describes the exercise program on a hospitalized 54-year-old male patient with cardiogenic shock waiting for a heart transplant assisted by an intra-aortic balloon pump, a temporary mechanical circulatory support device. The temporary mechanical circulatory support device, an intra-aortic balloon pump, was placed in the left subclavian artery, enabling the exercise protocol. Measurements and values from Swan-Ganz catheter, blood sample, brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP), as well as the six-minute walk test (6MWT) and venous oxygen saturation (SvO2) were obtained before and after an exercise protocol. The exercise training protocol involved the use of an unloaded bed cycle ergometer once a day, for a maximum of 30 minutes, to the tolerance limit. No adverse events or events related to the dislocation of the intra-aortic balloon pump were observed during the exercise protocol. The exercise program resulted in higher SvO2 levels, with an increased 6MWT with lower Borg dyspnea scores (312 meters vs. 488 meters and five points vs. three points, respectively). After completing the ten-day exercise protocol, the patient underwent a non-complicated heart transplant surgery and a full recovery in the ICU. This study showed that exercise is a feasible option for patients with cardiogenic shock who are using an intra-aortic balloon pump and that it is well-tolerated with no reported adverse events.


O presente relato de caso descreve o programa de exercícios aplicado a um paciente do sexo masculino, de 54 anos, internado com choque cardiogênico, aguardando transplante cardíaco e assistido por balão intra-aórtico, um dispositivo de suporte circulatório mecânico temporário. O dispositivo de suporte circulatório mecânico temporário, um balão intra-aórtico, foi colocado na artéria subclávia esquerda, possibilitando o protocolo de exercícios. Antes e após um protocolo de exercícios, foram obtidos dados a partir de cateter de Swan-Ganz, amostra de sangue, peptídeo natriurético cerebral (NT-proBNP), proteína C reativa de alta sensibilidade (PCR-as), teste de caminhada de seis minutos (TC6min) e medição da saturação venosa de oxigênio (SvO2). O protocolo de treinamento físico envolveu a utilização de um cicloergômetro adaptado ao leito, sem carga, uma vez ao dia, por no máximo 30 minutos, até o limite da tolerância. Não foram observados eventos adversos tampouco relacionados ao deslocamento do balão intra-aórtico durante o protocolo de exercícios. O programa de exercícios resultou em maior SvO2 com aumento do TC6min e menores escores de dispneia de Borg (312 metros vs. 488 metros e cinco pontos vs. três pontos, respectivamente). Após completar o protocolo de exercícios de dez dias, o paciente foi submetido a uma cirurgia de transplante cardíaco sem complicações e recuperação total na UTI. O presente estudo demonstrou que o exercício é uma opção viável para pacientes com choque cardiogênico em uso de balão intra-aórtico e que é bem tolerado, além de não haver relatos de eventos adversos.


Asunto(s)
Trasplante de Corazón , Corazón Auxiliar , Masculino , Humanos , Persona de Mediana Edad , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Trasplante de Corazón/efectos adversos , Caminata , Contrapulsador Intraaórtico/efectos adversos , Contrapulsador Intraaórtico/métodos , Corazón Auxiliar/efectos adversos , Resultado del Tratamiento
20.
Radiol Clin North Am ; 62(3): 453-471, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38553180

RESUMEN

Heart transplantation is a pivotal treatment of end-stage heart failure, and recent advancements have extended median posttransplant life expectancy. However, despite the progress in surgical techniques and medical treatment, heart transplant patients still face complications such as rejection, infections, and drug toxicity. CT is a reliable tool for detecting most of these complications, whereas MR imaging is particularly adept at identifying pericardial pathologies and signs of rejection. Awareness of these nuances by radiologists, cardiologists, and surgeons is desired to optimize care, reduce morbidities, and enhance survival.


Asunto(s)
Trasplante de Corazón , Radiología , Humanos , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/métodos , Radiografía , Imagen por Resonancia Magnética , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología
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