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2.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39273305

RESUMO

Amyloidosis diagnosis relies on Congo red staining with immunohistochemistry and immunofluorescence for subtyping but lacks sensitivity and specificity. Laser-microdissection mass spectroscopy offers better accuracy but is complex and requires extensive sample preparation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy offers a promising alternative for amyloidosis characterization. Cardiac tissue sections from nine patients with amyloidosis and 20 heart transplant recipients were analyzed using ATR-FTIR spectroscopy. Partial least squares discriminant analysis (PLS-DA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) models were used to differentiate healthy post-transplant cardiac tissue from amyloidosis samples and identify amyloidosis subtypes [κ light chain (n = 1), λ light chain (n = 3), and transthyretin (n = 5)]. Leave-one-out cross-validation (LOOCV) was employed to assess the performance of the PLS-DA model. Significant spectral differences were found in the 1700-1500 cm-1 and 1300-1200 cm-1 regions, primarily related to proteins. The PLS-DA model explained 85.8% of the variance, showing clear clustering between groups. PCA in the 1712-1711 cm-1, 1666-1646 cm-1, and 1385-1383 cm-1 regions also identified two clear clusters. The PCA and the HCA model in the 1646-1642 cm-1 region distinguished κ light chain, λ light chain, and transthyretin cases. This pilot study suggests ATR-FTIR spectroscopy as a novel, non-destructive, rapid, and inexpensive tool for diagnosing and subtyping amyloidosis. This study was limited by a small dataset and variability in measurements across different instruments and laboratories. The PLS-DA model's performance may suffer from overfitting and class imbalance. Larger, more diverse datasets are needed for validation.


Assuntos
Amiloidose , Análise de Componente Principal , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Projetos Piloto , Amiloidose/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Análise dos Mínimos Quadrados , Transplante de Coração , Análise por Conglomerados
3.
J Clin Apher ; 39(5): e22144, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39291764

RESUMO

Therapeutic plasma exchange (TPE) is a cornerstone treatment for antibody-mediated rejection (AMR) post-organ transplantation, aiming to eliminate pathogenic donor-specific HLA antibodies (DSA). However, limitations in HLA antibody interpretation due to the prozone-like effect (PLE) can lead to inaccurate assessment of treatment efficacy. We present a case of a heart transplant recipient with suspected AMR, where an unexpected increase in DSA levels post-TPE prompted investigation into PLE. Solid-phase Luminex assays were employed to detect HLA antibodies. Serum was run neat as well as after treatment with ethylenediaminetetraacetic acid (EDTA). Nephelometry was used to detect complement levels. Laboratory analysis of pre-TPE serum revealed higher DSA levels with EDTA treatment, characteristic of PLE. Complement measurements supported complement-mediated interference in the pre-TPE sample. This case underscores the importance of being aware that PLE can occur in HLA testing and can impact the interpretation of TPE efficacy for AMR.


Assuntos
Rejeição de Enxerto , Antígenos HLA , Transplante de Coração , Troca Plasmática , Humanos , Transplante de Coração/efeitos adversos , Troca Plasmática/métodos , Antígenos HLA/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/terapia , Rejeição de Enxerto/prevenção & controle , Masculino , Teste de Histocompatibilidade , Isoanticorpos/sangue , Pessoa de Meia-Idade
4.
Int J Mol Sci ; 25(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39273594

RESUMO

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced ageHTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes.


Assuntos
Ferro , Resposta a Proteínas não Dobradas , Zinco , Humanos , Zinco/metabolismo , Zinco/análise , Masculino , Ferro/metabolismo , Pessoa de Meia-Idade , Feminino , Adulto , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Estresse Oxidativo , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Idoso , Transplante de Coração , Coração Auxiliar/efeitos adversos , Aldeídos/metabolismo
5.
Nutrients ; 16(17)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39275161

RESUMO

INTRODUCTION: Heart transplantation is the standard treatment for severe heart failure. Graft preservation and infectious risk secondary to immunosuppressive drugs lead healthcare teams to offer nutritional advice to patients upon discharge from the hospital. However, no consensus or recommendation is available. METHOD: We conducted a study to review the practices in all 26 centers providing heart transplantation in French-speaking Europe. We requested and analyzed the written documents these centers provided to their patients. The same two dieticians categorized the highlighted pieces of advice into distinct, autonomous categories. RESULTS: We identified 116 pieces of advice, categorized into three areas: dietary restrictions for immunosuppressant/food interaction; environmental and food preparation guidelines and prevention of foodborne infections; and healthy and active lifestyle recommendations. Except for advice on immunosuppressant/food interaction, over one-third of the centers suggest discontinuing advice within 2 years post-transplant. General dietary advice covers lipids, carbohydrates, protein, calcium, sodium, and fiber but offers limited guidance on fatty acids despite their importance in cardiovascular risk prevention. CONCLUSION: This study represents a pioneering exploration of the nutritional advice provided to patients following cardiac transplantation. It underscores the critical necessity of establishing consensus-based clinical guidelines in this domain.


Assuntos
Transplante de Coração , Humanos , Transplante de Coração/efeitos adversos , Estudos Transversais , Europa (Continente) , Imunossupressores/efeitos adversos , Dieta
6.
Curr Opin Pediatr ; 36(5): 489-495, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39254752

RESUMO

PURPOSE OF REVIEW: This article highlights the most recent advances in a review of the current literature in the field of pediatric heart failure and transplantation. RECENT FINDINGS: Diagnostically, the identification of new genetic factors has contributed to a deeper understanding of cardiomyopathy in children. Novel medications like sacubitril/valsartan and Sodium-Glucose cotransporter-2 (SGLT2) inhibitors, which are now standard in the adult population are being studied in pediatric population and offer new promise of pediatric heart failure treatment. Ventricular assist devices are more commonly used in cardiomyopathy patients and single ventricle patients as a bridge to transplant. Recent pediatric heart transplant society (PHTS) data demonstrated that waitlist survival improved significantly over the past decades (i) and new treatments such as daratumumab and eculizumab have been used in high-risk populations and demonstrate promising results. TEAMMATE trial is the first multicenter randomized clinical trial (RCT) in pediatric heart transplant (HT) to evaluate the safety and efficacy of everolimus (EVL) and low-dose tacrolimus (TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). It will provide valuable information about the safety and efficacy of EVL, TAC, and MMF (ii).Donor cell-free DNA has been used more in pediatric transplant recipients and has significantly decreased invasive EMB (iii). SUMMARY: This past 5 years have witness dramatic progress in the field of pediatric heart failure and transplantation including more use of mechanical support in heart failure patients with various underlying etiology, especially use of mechanical support in single ventricle patients and the use of sacubitril/valsartan and SGLT2 inhibitors in the pediatric population. The problem of the highly sensitized transplant recipient remains, although novel therapeutics have been added to our toolbox of options to maintain healthy allograft function. Ongoing research aims to further enhance our understanding and management of pediatric heart failure, emphasizing the need for continued innovation in this complex field.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/tratamento farmacológico , Criança , Coração Auxiliar , Imunossupressores/uso terapêutico
7.
Pediatr Transplant ; 28(7): e14856, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39267498

RESUMO

BACKGROUND: Two common indications for pediatric heart transplantation are congenital heart disease and cardiomyopathy. Prior studies suggest differences in chronotropy on cardiopulmonary exercise testing outcomes depending on indication for heart transplantation. We aimed to determine whether the number of pretransplant sternotomies is associated with differences in heart rate response during exercise testing. METHODS: A retrospective analysis of our institutional pediatric heart transplant data between 2004 and 2022 was performed. Patients were categorized by indication for transplantation into a cardiomyopathy (CM) group if they had a congenital or acquired cardiomyopathy or a congenital heart disease (CHD) group including all other forms of congenital cardiac anatomic abnormalities. RESULTS: CHD patients (n = 40) differed from CM patients (n = 53) by mean number of sternotomies prior to transplant (2.4 ± 1.8 vs. 0.5 ± 0.9, p < 0.001). There were no significant differences in echocardiographic function or catheterization hemodynamics. In cardiopulmonary exercise testing performance, the congenital heart disease group had a significantly higher resting heart rate (91.8 ± 11.2 vs. 86.4 ± 10.2 bpm, p = 0.019), lower percent predicted age-predicted maximal heart rate achieved (78.3 ± 8.5% vs. 83.2 ± 11.4%, p = 0.032), and lower heart rate reserve (68.6 ± 19.8 vs. 84.4 ± 24.0 bpm, p = 0.001) despite a similar age and average time from transplantation. Regression analysis confirmed number of pretransplant sternotomies as a main predictor of heart rate metrics. CONCLUSIONS: There is greater chronotropic incompetence in patients who underwent transplantation due to congenital heart disease compared to cardiomyopathy. The groups differ significantly by number of sternotomies, potentially supporting the hypothesis that prior surgical disruption of cardiac innervation may cause decreased chronotropic response to exercise following transplantation.


Assuntos
Cardiomiopatias , Teste de Esforço , Cardiopatias Congênitas , Frequência Cardíaca , Transplante de Coração , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/fisiopatologia , Masculino , Feminino , Estudos Retrospectivos , Criança , Frequência Cardíaca/fisiologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/etiologia , Cardiomiopatias/diagnóstico , Adolescente , Pré-Escolar , Lactente , Exercício Físico/fisiologia
8.
Transpl Int ; 37: 12874, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267616

RESUMO

Non-adherence to immunosuppressive medication among transplant patients is associated with poor clinical outcomes and higher economic costs. Barriers to immunosuppressives are a proximal determinant of non-adherence. So far, international variability of barriers to adherence in transplantation has not been studied. As part of the cross-sectional multi-country and multi-center BRIGHT study, barriers to adherence were measured in 1,382 adult heart transplant recipients of 11 countries using the 28-item self-report questionnaire "Identifying Medication Adherence Barriers" (IMAB). Barriers were ranked by their frequency of occurrence for the total sample and by country. Countries were also ranked the by recipients' total number of barriers. Intra-class correlations were calculated at country and center level. The five most frequently mentioned barriers were sleepiness (27.1%), being away from home (25.2%), forgetfulness (24.5%), interruptions to daily routine (23.6%) and being busy (22.8%), fairly consistently across countries. The participants reported on average three barriers, ranging from zero up to 22 barriers. The majority of the variability among reported barriers frequency was situated at the recipient level (94.8%). We found limited international variability in primarily person-level barriers in our study. Understanding of barriers in variable contexts guides intervention development to support adherence to the immunosuppressive regimen in real-world settings.


Assuntos
Transplante de Coração , Imunossupressores , Adesão à Medicação , Humanos , Imunossupressores/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Idoso , Transplantados , Autorrelato , Rejeição de Enxerto/prevenção & controle , Análise de Dados Secundários
9.
Clin Transplant ; 38(9): e15419, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39235071

RESUMO

PURPOSE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.


Assuntos
Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Sobrevivência de Enxerto , Transplante de Coração , Humanos , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/epidemiologia , Feminino , Masculino , Citomegalovirus/isolamento & purificação , Seguimentos , Adulto , Prognóstico , Estudos Retrospectivos , Antivirais/uso terapêutico , Fatores de Risco , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Taxa de Sobrevida , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Doadores de Tecidos/provisão & distribuição
10.
Clin Transplant ; 38(9): e15456, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39229694

RESUMO

BACKGROUND: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. METHODS: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. RESULTS: Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post-transplant overall survival or graft survival. CONCLUSIONS: The benefits of reducing waitlist time while preserving post-transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques.


Assuntos
Sobrevivência de Enxerto , Transplante de Coração , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Transplante de Coração/mortalidade , Masculino , Feminino , Prognóstico , Doadores de Tecidos/provisão & distribuição , Seguimentos , Pessoa de Meia-Idade , Taxa de Sobrevida , Viagem/estatística & dados numéricos , Adulto , Fatores de Risco , Estados Unidos
11.
Exp Clin Transplant ; 22(7): 540-550, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39223812

RESUMO

OBJECTIVES: Chronic rejection remains the leading cause of progressive decline in graft function. Accumulating evidence indicates that macrophages participate in chronic rejection dependent on CD40-CD40L. The FOS family members are critical in inflammatory and immune responses. However, the mechanisms underlying the role of FOS family members in chronic rejection remain unclear. In this study, we aimed to elucidate the role and underlying mechanisms of FOS-positive macrophages regulated by CD40 that mediate chronic allograft rejection. MATERIALS AND METHODS: We downloaded publicly accessible chronic rejection kidney transplant single-cell sequencing datasets from the gene expression omnibus database. Differentially expressed genes between the CD40hi and CD40low macrophage chronic rejection groups were analyzed. We established a chronic rejection mouse model by using CTLA-4-Ig. We treated bone marrow-derived macrophages with an anti-CD40 antibody. We assessed expression of the FOS family by flow cytometry, real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. We identified altered signaling pathways by using RNA sequencing analysis. We detected DNA specifically bound to transcription factors by using ChIP-sequencing, with detection of the degree of graft fibrosis and survival. RESULTS: FOS was highly expressed on CD40hi macrophages in patients with chronic transplantrejection. Mechanistically, we showed that CD40 activated NF-κB2 translocation into the nucleus to upregulate c-Fos and FosB expression, thus promoting chronic rejection of cardiac transplant.We showed thatNF-κB2 regulated c-Fos and FosB expression by binding to the c-fos and fosb promoter regions. Inhibition of c-Fos/activator protein-1 decreased graft fibrosis and prolonged graft survival. CONCLUSIONS: CD40 may activate transcription factor NF-κB2 translocation into the nucleus of macrophages to upregulate c-Fos and FosB expression, thus promoting chronic rejection of cardiac transplant. Inhibition of c-Fos/activator protein-1 decreased grafts fibrosis and prolonged graft survival.


Assuntos
Antígenos CD40 , Modelos Animais de Doenças , Rejeição de Enxerto , Transplante de Coração , Macrófagos , Proteínas Proto-Oncogênicas c-fos , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Antígenos CD40/metabolismo , Antígenos CD40/genética , Células Cultivadas , Doença Crônica , Bases de Dados Genéticas , Fibrose , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/genética , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Fator de Transcrição AP-1/metabolismo
12.
Clin Cardiol ; 47(9): e70010, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233528

RESUMO

OBJECTIVE: This study aimed to investigate the impact of the donor-recipient BMI ratio on the survival outcomes of heart transplant recipients. METHODS: A retrospective analysis was conducted on 641 heart transplant patients who underwent surgery between September 2008 and June 2021. The BMI ratio (donor BMI divided by recipient BMI) was calculated for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to evaluate survival rates and determine the hazard ratio (HR) for mortality. RESULTS: Significant differences were found in donor age and donor-recipient height ratio between the BMI ratio groups. The BMI ratio ≥ 1 group had a higher mean donor age (37.27 ± 10.54 years) compared to the BMI ratio < 1 group (34.72 ± 11.82 years, p = 0.008), and a slightly higher mean donor-recipient height ratio (1.02 ± 0.06 vs. 1.00 ± 0.05, p = 0.002). The Kaplan-Meier survival analysis indicated that the survival rate in the BMI ratio ≥ 1 group was significantly lower than in the BMI ratio < 1 group. Cox multivariate analysis, adjusted for confounding factors, revealed a HR of 1.50 (95% CI: 1.08-2.09) for mortality in patients with a BMI ratio ≥ 1. No significant differences were observed in ICU stay, postoperative hospitalization days, or total mechanical ventilation time between the groups. CONCLUSION: A higher donor-recipient BMI ratio was associated with an increased risk of mortality in heart transplant recipients.


Assuntos
Índice de Massa Corporal , Transplante de Coração , Doadores de Tecidos , Humanos , Estudos Retrospectivos , Feminino , Masculino , Adulto , Doadores de Tecidos/estatística & dados numéricos , Taxa de Sobrevida/tendências , Fatores de Risco , Pessoa de Meia-Idade , Seguimentos , Fatores de Tempo , Resultado do Tratamento
13.
Braz J Cardiovasc Surg ; 39(5): e20230394, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39241193

RESUMO

INTRODUCTION: Heart transplantation is the gold standard for advanced heart failure treatment. This study examines the survival rates and risk factors for early mortality in adult heart transplant recipients at a Brazilian center. METHODS: This retrospective cohort study involved 255 adult heart transplant patients from a single center in Brazil. Data were collected from medical records and databases including three defined periods (2012-2015, 2016-2019, and 2020-2022). Statistical analysis employed Kaplan-Meier survival curves, Cox proportional hazards analysis for 30-day mortality risk factors, and Log-rank tests. RESULTS: The recipients were mostly male (74.9%), and the mean age was 46.6 years. Main causes of heart failure were idiopathic dilated cardiomyopathy (33.9%), Chagas cardiomyopathy (18%), and ischemic cardiomyopathy (14.3%). The study revealed an overall survival of 68.1% at one year, 58% at five years, and 40.8% at 10 years after heart transplantation. Survivalimproved significantly over time, combining the most recent periods (2016 to 2022) it was 73.2% in the first year and 63% in five years. The main risk factors for 30-day mortality were longer time on cardiopulmonary bypass, the initial period of transplants (2012 to 2015), older age of the donor, and nutritional status of the donor (overweight or obese). The main causes of death within 30 days post-transplant were infection and primary graft dysfunction. CONCLUSION: The survival analysis by period demonstrated that the increased surgical volume, coupled with the team's experience and modifications to the immunosuppression protocol, contributed to the improved early and mid-term outcomes.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Humanos , Masculino , Transplante de Coração/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Brasil/epidemiologia , Adulto , Fatores de Risco , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Estimativa de Kaplan-Meier , Taxa de Sobrevida , Análise de Sobrevida , Fatores de Tempo , Modelos de Riscos Proporcionais
14.
Rev Med Liege ; 79(9): 559-566, 2024 Sep.
Artigo em Francês | MEDLINE | ID: mdl-39262362

RESUMO

Heart failure (HF) is a major public health problem in our country and in most developed countries. Despite advances in the diagnosis and management of this condition and numerous therapeutic innovations, many patients with chronic HF progress inexorably to advanced HF, characterized by persistent symptoms despite maximal treatment. The prognosis for this condition is poor. However, mechanical circulatory support and heart transplantation, when considered in suitable candidates, are likely to improve the quality of life and life expectancy of these patients. In this context, timely referral to referral centers for the management of advanced HF is crucial. This article reminds the definition of advanced HF, details its specific management and specifies the criteria and timing for appropriate referral.


L'insuffisance cardiaque (IC) est un problème de santé publique majeur au sein de notre pays et dans la plupart des pays développés. Malgré les progrès réalisés dans le diagnostic et la prise en charge de cette pathologie ainsi que les nombreuses innovations thérapeutiques, beaucoup de patients atteints d'IC progressent inexorablement vers une IC avancée, caractérisée par la persistance de symptômes en dépit d'un traitement maximal. Le pronostic de cette condition est sombre. Cependant, les assistances mécaniques circulatoires et la transplantation cardiaque, lorsqu'elles sont envisagées chez de bons candidats, sont susceptibles d'améliorer la qualité de vie et l'espérance de vie de ces patients. Dans cette optique, le référencement selon un timing adéquat vers des centres de référence de prise en charge de l'IC avancée est crucial. Cet article revient sur la définition de l'IC avancée, détaille sa prise en charge spécifique et précise les critères et le timing pour un référencement adéquat.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Transplante de Coração , Prognóstico , Qualidade de Vida , Coração Auxiliar
15.
Kardiologiia ; 64(7): 72-76, 2024 Jul 31.
Artigo em Russo | MEDLINE | ID: mdl-39102576

RESUMO

The prognosis after heart transplantation continues to improve. Therefore, the prevention of chronic post-transplant sequelae, such as chronic kidney disease, allograft vasculopathy, and malignancies is becoming increasingly important. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used for immunosuppression after heart transplantation. However, everolimus may cause a characteristic complex of adverse effects, including dyslipidemia. Currently there are no guidelines for the long-term screening and treatment of dyslipidemia in heart transplant recipients treated with everolimus. This article presents a clinical case of hypercholesterolemia that developed after the start of the everolimus treatment in a heart recipient. The patient was a 39-year-old man who underwent orthotopic heart transplantation for ischemic cardiomyopathy in 2012 (at the age of 27). In 2019, the patient's immunosuppressive therapy was converted from mycophenolate mofetil to everolimus due to the development of cardiac allograft vasculopathy. The change in the immunosuppressive therapy was associated with increases in total cholesterol and low-density lipoprotein cholesterol, which were not reversed with a combined lipid-lowering therapy (maximum doses of rosuvastatin, ezetimibe, fenofibrate). A decrease in lipid levels was achieved with a blocker of hepatic proprotein convertase subtilisin/kexin type 9 synthesis at the level of microribonucleic acid (inclisiran). This case demonstrates the difficulties in correcting dyslipidemia in patients with cardiac allograft, since the treatment with the immunosuppressant everolimus worsens existing dyslipidemia. However, the combination lipid-lowering therapy, that affects various elements of the pathogenesis (specifically, the combined inhibition of hydroxymethylglutaryl-CoA reductase with a statin, cholesterol absorption from the small intestine with ezetimibe, and PCSK9 messenger RNA with inclisiran), provides an effective control of blood lipids and minimizing the adverse effects of immunosuppressive therapy, such as cardiac allograft vasculopathy.


Assuntos
Everolimo , Transplante de Coração , Humanos , Masculino , Adulto , Everolimo/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Inibidores de PCSK9 , Complicações Pós-Operatórias/tratamento farmacológico , Resultado do Tratamento , RNA Interferente Pequeno
16.
Heart Fail Rev ; 29(5): 1079-1096, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39093495

RESUMO

Due to the discrepancy between patients awaiting a heart transplant and the availability of donor hearts, strategies to expand the donor pool and improve the transplant's success are crucial. This review aims to summarize current knowledge on the ex vivo heart preservation (EVHP) experience as an alternative to standard cold static storage (CSS). EVHP techniques can improve the preservation of the donor's heart before transplantation and allow for pre-transplant organ evaluation.


Assuntos
Transplante de Coração , Preservação de Órgãos , Perfusão , Humanos , Transplante de Coração/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos
17.
J Am Coll Cardiol ; 84(7): 620-632, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39111968

RESUMO

BACKGROUND: In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy. OBJECTIVES: This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks. METHODS: Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality. RESULTS: Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order. CONCLUSIONS: The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed.


Assuntos
Transplante de Coração , Listas de Espera , Humanos , Listas de Espera/mortalidade , Transplante de Coração/mortalidade , Criança , Masculino , Feminino , Pré-Escolar , Lactente , Adolescente , Estados Unidos/epidemiologia , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Estudos Retrospectivos
18.
J Am Coll Cardiol ; 84(7): 633-634, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39111969
19.
Clin Transplant ; 38(8): e15420, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113661

RESUMO

BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Coração , Terapia de Imunossupressão , Imunossupressores , Humanos , Masculino , Feminino , Estudos Retrospectivos , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Pessoa de Meia-Idade , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Prognóstico , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Adulto , Complicações Pós-Operatórias , Taxa de Sobrevida , Transplante de Fígado/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Coração-Pulmão/mortalidade , Fatores de Risco , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Gerenciamento Clínico
20.
Clin Transplant ; 38(8): e15422, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39115465

RESUMO

BACKGROUND: This study evaluates the clinical trends, risk factors, and impact of waitlist blood transfusion on outcomes following isolated heart transplantation. METHODS: The UNOS registry was queried to identify adult recipients from January 1, 2014, to June 30, 2022. The recipients were stratified into two groups depending on whether they received a blood transfusion while on the waitlist. The incidence of waitlist transfusion was compared before and after the 2018 allocation policy change. The primary outcome was survival. Propensity score-matching was performed. Multivariable logistic regression was performed to identify predictors of waitlist transfusion. A sub-analysis was performed to evaluate the impact of waitlist time on waitlist transfusion. RESULTS: From the 21 926 recipients analyzed in this study, 4201 (19.2%) received waitlist transfusion. The incidence of waitlist transfusion was lower following the allocation policy change (14.3% vs. 23.7%, p < 0.001). The recipients with waitlist transfusion had significantly reduced 1-year posttransplant survival (88.8% vs. 91.9%, p < 0.001) compared to the recipients without waitlist transfusion in an unmatched comparison. However, in a propensity score-matched comparison, the two groups had similar 1-year survival (90.0% vs. 90.4%, p = 0.656). Multivariable analysis identified ECMO, Impella, and pretransplant dialysis as strong predictors of waitlist transfusion. In a sub-analysis, the odds of waitlist transfusion increased nonlinearly with longer waitlist time. CONCLUSION: There is a lower incidence of waitlist transfusion among transplant recipients under the 2018 allocation system. Waitlist transfusion is not an independent predictor of adverse posttransplant outcomes but rather a marker of the patient's clinical condition. ECMO, Impella, and pretransplant dialysis are strong predictors of waitlist transfusion.


Assuntos
Transfusão de Sangue , Transplante de Coração , Sistema de Registros , Listas de Espera , Humanos , Masculino , Listas de Espera/mortalidade , Feminino , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Pessoa de Meia-Idade , Seguimentos , Fatores de Risco , Prognóstico , Taxa de Sobrevida , Transfusão de Sangue/estatística & dados numéricos , Sobrevivência de Enxerto , Adulto , Estudos Retrospectivos
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