RESUMEN
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.
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Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , Supervivencia de Injerto , Trasplante de Corazón , Humanos , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/epidemiología , Femenino , Masculino , Citomegalovirus/aislamiento & purificación , Estudios de Seguimiento , Adulto , Pronóstico , Estudios Retrospectivos , Antivirales/uso terapéutico , Factores de Riesgo , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Tasa de Supervivencia , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Donantes de Tejidos/provisión & distribuciónRESUMEN
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.
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Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Masculino , Trasplante de Corazón/mortalidad , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Brasil/epidemiología , Adulto , Factores de Riesgo , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Estimación de Kaplan-Meier , Tasa de Supervivencia , Análisis de Supervivencia , Factores de Tiempo , Modelos de Riesgos ProporcionalesRESUMEN
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.
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Antígenos CD40 , Modelos Animales de Enfermedad , Rechazo de Injerto , Trasplante de Corazón , Macrófagos , Proteínas Proto-Oncogénicas c-fos , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Antígenos CD40/metabolismo , Antígenos CD40/genética , Células Cultivadas , Enfermedad Crónica , Bases de Datos Genéticas , Fibrosis , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Rechazo de Injerto/genética , Supervivencia de Injerto , Trasplante de Corazón/efectos adversos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Factor de Transcripción AP-1/metabolismoRESUMEN
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.
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Trasplante de Corazón , Inmunosupresores , Cumplimiento de la Medicación , Humanos , Inmunosupresores/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Anciano , Receptores de Trasplantes , Autoinforme , Rechazo de Injerto/prevención & control , Análisis de Datos SecundariosRESUMEN
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.
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Índice de Masa Corporal , Trasplante de Corazón , Donantes de Tejidos , Humanos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Donantes de Tejidos/estadística & datos numéricos , Tasa de Supervivencia/tendencias , Factores de Riesgo , Persona de Mediana Edad , Estudios de Seguimiento , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Cardiomiopatías , Prueba de Esfuerzo , Cardiopatías Congénitas , Frecuencia Cardíaca , Trasplante de Corazón , Humanos , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/fisiopatología , Masculino , Femenino , Estudios Retrospectivos , Niño , Frecuencia Cardíaca/fisiología , Cardiomiopatías/fisiopatología , Cardiomiopatías/etiología , Cardiomiopatías/diagnóstico , Adolescente , Preescolar , Lactante , Ejercicio Físico/fisiologíaRESUMEN
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.
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Amiloidosis , Análisis de Componente Principal , Humanos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Proyectos Piloto , Amiloidosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Análisis de los Mínimos Cuadrados , Trasplante de Corazón , Análisis por ConglomeradosRESUMEN
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.
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Hierro , Respuesta de Proteína Desplegada , Zinc , Humanos , Zinc/metabolismo , Zinc/análisis , Masculino , Hierro/metabolismo , Persona de Mediana Edad , Femenino , Adulto , Cardiotoxicidad/etiología , Cardiotoxicidad/metabolismo , Estrés Oxidativo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Anciano , Trasplante de Corazón , Corazón Auxiliar/efectos adversos , Aldehídos/metabolismoRESUMEN
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.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/diagnóstico , Trasplante de Corazón , Pronóstico , Calidad de Vida , Corazón AuxiliarRESUMEN
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.
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Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/tratamiento farmacológico , Niño , Corazón Auxiliar , Inmunosupresores/uso terapéuticoRESUMEN
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.
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Trasplante de Corazón , Humanos , Trasplante de Corazón/efectos adversos , Estudios Transversales , Europa (Continente) , Inmunosupresores/efectos adversos , DietaRESUMEN
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.
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Supervivencia de Injerto , Trasplante de Corazón , Donantes de Tejidos , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Trasplante de Corazón/mortalidad , Masculino , Femenino , Pronóstico , Donantes de Tejidos/provisión & distribución , Estudios de Seguimiento , Persona de Mediana Edad , Tasa de Supervivencia , Viaje/estadística & datos numéricos , Adulto , Factores de Riesgo , Estados UnidosRESUMEN
PURPOSE OF REVIEW: Mechanical circulatory support is used frequently as a method of stabilizing patients with end stage heart failure who are unable to safely await allograft availability. While this technology has been fundamentally important in supporting patients with normal cardiac anatomy, it is still used infrequently in adult patients with congenital heart disease and end-stage heart failure. Here, we review the data on mechanical circulatory support technology in this small but growing population of patients with chronic heart disease prone to the development of circulatory failure. RECENT FINDINGS: Mechanical circulatory support (MCS) has been increasingly employed in adults with congenital heart disease (ACHD) as a bridge to transplant. The new United Network for Organ Sharing listing system favoring temporary MCS use with a higher listing status offers another tool to stabilize ACHD patients and potentially shorten wait times. Both temporary and Durable MCS could help improve transplant candidacy and posttransplant outcomes in select groups of ACHD patients. SUMMARY: Durable and temporary MCS have the potential to significantly improve access to transplant and overall transplant outcomes in ACHD patients.
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Cardiopatías Congénitas , Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Listas de Espera , Humanos , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/terapia , Cardiopatías Congénitas/fisiopatología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Adulto , Resultado del Tratamiento , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE OF REVIEW: With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients. RECENT FINDINGS: The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool. SUMMARY: The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.
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Cardiopatías Congénitas , Trasplante de Corazón , Preservación de Órganos , Perfusión , Humanos , Preservación de Órganos/métodos , Preservación de Órganos/efectos adversos , Trasplante de Corazón/métodos , Cardiopatías Congénitas/cirugía , Perfusión/métodos , Perfusión/efectos adversos , Resultado del Tratamiento , Donantes de Tejidos/provisión & distribución , Selección de Donante , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/fisiopatologíaRESUMEN
BACKGROUND: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes. METHODS AND RESULTS: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, ß, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL-1; P=0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P=0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was ß (P=0.038). CONCLUSIONS: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.
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Procedimiento de Fontan , Ventrículos Cardíacos , Fenotipo , Humanos , Procedimiento de Fontan/efectos adversos , Preescolar , Masculino , Femenino , Niño , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/anomalías , Estudios Prospectivos , Resultado del Tratamiento , Cateterismo Cardíaco , Función Ventricular Derecha/fisiología , Trasplante de Corazón , Metaloproteinasa 2 de la Matriz/sangre , Corazón Univentricular/cirugía , Corazón Univentricular/fisiopatología , Corazón Univentricular/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: This case report documents the first worldwide use of the Hybrid System from Spectrum Medical in a heart transplant procedure, focusing on its safety and efficacy. Traditional cardiopulmonary bypass systems often use an open reservoir, which increases the blood's exposure to air, thereby heightening the risk of an inflammatory response and gas embolism. In contrast, the Hybrid System is designed to improve surgical outcomes by significantly reducing the blood-air interface. This system utilizes a dual-chamber cardiotomy-venous reservoir with a collapsible soft bag, effectively minimizing blood contact with air and foreign materials. However, it is important to note that there is currently no evidence supporting the use of this methodology specifically in heart transplants. CASE PRESENTATION: A 41-year-old male managed with a left ventricular assist device because of dilated cardiomyopathy underwent a heart transplant using the Hybrid System. The perioperative and postoperative data provided evidence of the system's effectiveness. The selection of this patient was due to the absence of significant comorbidities unrelated to his primary cardiac condition, making him an ideal candidate to evaluate the system's performance. CONCLUSION: The Hybrid System is safe and efficient. The successful implementation in this case highlights its advantages over traditional cardiopulmonary bypass systems, suggesting a promising future in cardiac surgery. Further studies with routine cardiac surgery patients are required to validate these findings.
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Circulación Extracorporea , Trasplante de Corazón , Humanos , Masculino , Trasplante de Corazón/métodos , Adulto , Circulación Extracorporea/métodos , Corazón Auxiliar , Cardiomiopatía Dilatada/cirugíaRESUMEN
Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 17-year-old boy with hemodynamic derangement and cardiac arrest due to fulminant myocarditis. After about 2 h of intensive cardiopulmonary resuscitation, with 13 days of extracorporeal membrane oxygenation support, the patient finally bridged to orthotopic heart transplantation. The patient recovered uneventfully and was discharged 37 days after transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls confirming the diagnosis and identifying the underlying cause of fulminant myocarditis.
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Oxigenación por Membrana Extracorpórea , Trasplante de Corazón , Miocarditis , Humanos , Masculino , Miocarditis/cirugía , Adolescente , Oxigenación por Membrana Extracorpórea/métodos , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Corazón AuxiliarRESUMEN
Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1ß, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear. While the role of microbial and cell death products has been previously described, we identified alloreactive memory CD4 T cells as the primary triggers of innate inflammation. Memory CD4 T cells engaged MHC II-mismatched dendritic cells (DCs), leading to the production of innate inflammatory cytokines. This innate inflammation was independent of several pattern recognition receptors and was primarily driven by TNF superfamily ligands expressed by alloreactive memory CD4 T cells. Blocking of CD40L and TNFα resulted in dampened inflammation, and mice genetically deficient in these molecules exhibited prolonged survival of cardiac allografts. Furthermore, myeloid cell and CD8 T cell infiltration into cardiac transplants was compromised in both CD40L- and TNFα-deficient recipients. Strikingly, we found that priming of naive alloreactive CD8 T cells was dependent on licensing of DCs by memory CD4 T cells. This study unravels the key mechanisms by which alloreactive memory CD4 T cells contribute to destructive pathology and transplant rejection.