RESUMEN
BACKGROUND: Women with thoracic aortic aneurysms within the arch or descending thoracic aorta have poorer survival than men. Sex differences in relative thoracic aortic aneurysm size may account for some of the discrepancy. The aim of this study was to explore whether basing clinical management on aneurysm size index (maximum aneurysm diameter/body surface area) rather than aneurysm size can restore equality of survival by sex. METHODS: The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA; ISRCTN04044627) study was a prospective, observational cohort study. Adults referred to National Health Service hospitals in England with new/existing arch or descending thoracic aorta aneurysms greater than or equal to 4 cm in diameter were followed from March 2014 to March 2022. Baseline characteristics and survival to intervention and overall were compared for men and women. Survival models were used to assess the association between all-cause survival and sex, with and without adjustment for aneurysm diameter or aneurysm size index. RESULTS: A total of 886 thoracic aortic aneurysm patients were recruited: 321 (36.2%) women and 565 (63.8%) men. The mean(s.d.) aneurysm diameter was the same for women and men (5.7(1.1) versus 5.7(1.2) cm respectively; P = 0.751), but the mean(s.d.) aneurysm size index was greater for women than for men (3.32(0.80) versus 2.83(0.63) respectively; P < 0.001). Women had significantly worse survival without intervention: 110 (34.3%) women and 135 (23.9%) men (log rank test, P < 0.001). All-cause mortality remained greater for women after adjustment for diameter (HR 1.65 (95% c.i. 1.35 to 2.02); P < 0.001), but was attenuated after adjustment for aneurysm size index (HR 1.11 (95% c.i. 0.89 to 1.38); P = 0.359). Similar results were found for all follow-up, with or without intervention, and findings were consistent for descending thoracic aorta aneurysms alone. CONCLUSION: Guidelines for referral to specialist services should consider including aneurysm size index rather than diameter to reduce inequity due to patient sex.
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Aneurisma de la Aorta Torácica , Humanos , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/terapia , Femenino , Masculino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Inglaterra/epidemiología , Factores Sexuales , Disparidades en Atención de Salud/estadística & datos numéricos , Aorta Torácica/patologíaRESUMEN
BACKGROUND: Surgical intervention for thoracic aortic aneurysms is high risk. Understanding changes in health-related quality of life before and after endovascular stent grafting and open surgical repair can aid treatment decision-making. METHODS: The Effective Treatments for Thoracic Aortic Aneurysms ('ETTAA') study (ISRCTN04044627) was a longitudinal, observational study. Adults with new/existing arch or descending thoracic aortic aneurysms greater than or equal to 4â cm in diameter were followed from 2014 to 2022. Five domains of health-related quality of life (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) were recorded using the EuroQoL, five dimensions, five levels ('EQ-5D-5L') questionnaire and analysed using a range of longitudinal mixed models. RESULTS: Of 886 thoracic aortic aneurysm participants, 824 completed at least 2 questionnaires. Patients had slightly worse health-related quality of life than age-matched norms. Without surgery, deterioration occurred over time in Mobility (0.072/year (95% c.i. 0.042 to 0.101), P < 0.001) and Self-Care (0.039/year (95% c.i. 0.018 to 0.061), P < 0.001) in both sexes and Pain/Discomfort in women (0.069/year (95% c.i. 0.020 to 0.118), P = 0.005). For 6 weeks after endovascular stent grafting, there was a significant impairment in Self-Care (0.214 (95% c.i. 0.112 to 0.316), P < 0.001) and (for women only) in Usual Activities (0.625 (95% c.i. 0.338 to 0.911), P < 0.001), which then returned to pre-endovascular stent grafting levels. Six weeks after open surgical repair, the impairment in health-related quality of life was greater (Mobility 0.492 (95% c.i. 0.314 to 0.669), Self-Care 0.474 (95% c.i. 0.364 to 0.583), Usual Activities 1.469 (95% c.i. 1.042 to 1.896), and Pain/Discomfort 0.561 (95% c.i. 0.363 to 0.760), all P < 0.001) and took longer to return to pre-open surgical repair levels, partly due to increased complications and longer hospitalization. Anxiety/Depression decreased after open surgical repair (-0.214 (95% c.i. -0.326 to -0.101), P < 0.001). Age, sex, frailty, smoking, New York Heart Association class, and chronic obstructive pulmonary disease were significantly associated with health-related quality of life. CONCLUSION: Without intervention, health-related quality of life declines as age increases. Changes in health-related quality of life should contribute to surgical treatment decision-making.
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Aneurisma de la Aorta Torácica , Calidad de Vida , Humanos , Masculino , Femenino , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/psicología , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Procedimientos Endovasculares/métodos , Encuestas y Cuestionarios , Anciano de 80 o más AñosRESUMEN
Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.
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Trasplante de Corazón , Humanos , Trasplante de Corazón/métodos , Preservación de Órganos/métodos , Obtención de Tejidos y Órganos/métodos , Animales , Perfusión/métodos , Donantes de Tejidos , Metabolismo EnergéticoRESUMEN
Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term.
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Trasplante de Corazón , Obtención de Tejidos y Órganos , Humanos , Supervivencia de Injerto , Estudios Retrospectivos , Incidencia , Volumen Sistólico , Función Ventricular Izquierda , Donantes de Tejidos , Muerte Encefálica , Trasplante de Corazón/efectos adversos , Aloinjertos , MuerteRESUMEN
BACKGROUND: Heart transplantation (HTx) after donation after circulatory death (DCD) is an expanding practice but is associated with increased warm ischemic time. The impact of DCD HTx on cardiac mechanics and myocardial fibrosis has not been reported. We aimed to compare cardiac mechanics and myocardial fibrosis using cardiovascular magnetic resonance (CMR) imaging in donation after brain death (DBD) and DCD HTx recipients and healthy controls. METHODS AND RESULTS: Consecutive HTx recipients between March 2015 and March 2021 who underwent routine surveillance CMR imaging were included. Cardiac mechanics were assessed using CMR feature tracking to compute global longitudinal strain, global circumferential strain, and right ventricular free-wall longitudinal myocardial strain. Fibrosis was assessed using late gadolinium enhancement imaging and estimation of extracellular volume. There were 82 (DBD nâ¯=â¯42, DCD nâ¯=â¯40) HTx recipients (aged 53 years, interquartile range 41-59 years, 24% female) who underwent CMR imaging at median of 9 months (interquartile range 6-14 months) after transplantation. HTx recipients had increased extracellular volume (29.7 ± 3.6%) compared with normal ranges (25.9%, interquartile range 25.4-26.5). Myocardial strain was impaired after transplantation compared with controls (global longitudinal strain -12.6 ± 3.1% vs -17.2 ± 1.8%, P < .0001; global circumferential strain -16.9 ± 3.1% vs -19.2 ± 2.0%, Pâ¯=â¯.002; right ventricular free-wall longitudinal strain -15.7 ± 4.5% vs -21.6 ± 4.7%, P < .0001). There were no differences in fibrosis burden (extracellular volume 30.6 ± 4.4% vs 29.2 ± 3.2%; Pâ¯=â¯.39) or cardiac mechanics (global longitudinal strain -13.1 ± 3.0% vs -12.1 ± 3.1%, Pâ¯=â¯.14; global circumferential strain -17.3 ± 2.9% vs -16.6 ± 3.1%, Pâ¯=â¯.27; right ventricular free-wall longitudinal strain -15.9 ± 4.9% vs -15.5 ± 4.1%, Pâ¯=â¯.71) between DCD and DBD HTx. CONCLUSIONS: HTx recipients have impaired cardiac mechanics compared with controls, with increased myocardial fibrosis. There were no differences in early CMR imaging characteristics between DBD and DCD heart transplants, providing further evidence that DCD and DBD HTx outcomes are comparable.
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Cardiomiopatías , Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Femenino , Masculino , Medios de Contraste , Gadolinio , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Fibrosis , Estudios Retrospectivos , Donantes de TejidosRESUMEN
AIMS: To observe, describe, and evaluate management and timing of intervention for patients with untreated thoracic aortic aneurysms. METHODS AND RESULTS: Prospective study of UK National Health Service (NHS) patients aged ≥18 years, with new/existing arch or descending thoracic aortic aneurysms of ≥4 cm diameter, followed up until death, intervention, withdrawal, or July 2019. Outcomes were aneurysm growth, survival, quality of life (using the EQ-5D-5L utility index), and hospital admissions. Between 2014 and 2018, 886 patients were recruited from 30 NHS vascular/cardiothoracic units. Maximum aneurysm diameter was in the descending aorta in 725 (82%) patients, growing at 0.2 cm (0.17-0.24) per year. Aneurysms of ≥4 cm in the arch increased by 0.07 cm (0.02-0.12) per year. Baseline diameter was related to age and comorbidities, and no clinical correlates of growth were found. During follow-up, 129 patients died, 64 from aneurysm-related events. Adjusting for age, sex, and New York Heart Association dyspnoea index, risk of death increased with aneurysm size at baseline [hazard ratio (HR): 1.88 (95% confidence interval: 1.64-2.16) per cm, P < 0.001] and with growth [HR: 2.02 (1.70-2.41) per cm, P < 0.001]. Hospital admissions increased with aneurysm size [relative risk: 1.21 (1.05-1.38) per cm, P = 0.008]. Quality of life decreased annually for each 10-year increase in age [-0.013 (-0.019 to -0.007), P < 0.001] and for current smoking [-0.043 (-0.064 to -0.023), P = 0.004]. Aneurysm size was not associated with change in quality of life. CONCLUSION: International guidelines should consider increasing monitoring intervals to 12 months for small aneurysms and increasing intervention thresholds. Individualized decisions about surveillance/intervention should consider age, sex, size, growth, patient characteristics, and surgical risk.
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Aneurisma de la Aorta Torácica , Adolescente , Adulto , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Estudios de Seguimiento , Humanos , Estudios Prospectivos , Calidad de Vida , Medicina EstatalRESUMEN
Donation after circulatory death in the context of heart transplants is attracting interest and becoming popular in clinical practice. Activity is growing in the United Kingdom, Australia, and the United States. We believe that a prolonged warm ischemic time (time from asystole to reperfusion of the heart on an ex vivo perfusion system) is a primary indicator of adverse outcomes. However, 1.5 liters of blood must be retrieved from the right atrium following sternotomy prolonging warm ischemic time. The patient in the following case report was supported by veno-venous extra-corporeal membrane oxygenation following drowning, further complicated by aspiration-related lung failure. Following circulatory death and a mandatory five-minute stand-off period, 1.5 liters of blood was drained from the circuit as sternotomy began. Surgeons then proceeded to direct procurement of the heart, aiming for least functional warm ischemic time. Following standard implantation, the patient's postoperative recovery has been unremarkable to date.
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Sistema Cardiovascular , Oxigenación por Membrana Extracorpórea , Trasplante de Corazón , Obtención de Tejidos y Órganos , Adulto , Humanos , Donantes de Tejidos , Circulación Extracorporea , PerfusiónRESUMEN
BACKGROUND AND AIM OF THE STUDY: An atrioesophageal fistula is a devastating complication of ablation for atrial fibrillation. For the surgeon facing this dreaded complication, it may be a 'once in a lifetime' case. This review aims to describe the clinical problem and evaluate the outcome of different surgical techniques to start guiding cardiothoracic surgeons toward those which offer the best chance of survival. METHODS: An electronic search retrieved 125 articles containing 195 cases of atrioesophageal fistula secondary to atrial fibrillation ablation. Reports of pericardio-esophageal or mediastino-esophageal fistula were excluded. RESULTS: The median age was 61 and 143 (73%) cases occurred in males. Fever (n = 147; 75%) and neurological dysfunction (n = 151; 77%) were the most common symptoms. The median time from ablation to symptom onset was 21 days (interquartile range: 12-28). The most sensitive thoracic imaging modality was computed tomography (n = 135/153; 90%). Immediate deterioration occurred during 11/58 (19%) oesophago-gastro-duodenoscopies. Mortality was lower in patients who had surgery (39%) compared with endoscopic intervention (94%) or conservative management (97%). Patients who had atrial repair combined with esophageal repair or oesophagectomy were more likely to survive than those who had atrial repair alone (OR 6.97; p < .001). Isolation of the esophageal aspect of the fistula conferred an additional survival benefit (OR 5.85; p = .02). CONCLUSIONS: Fever, neurological symptoms, and chest pain in the context of recent ablation should prompt immediate evaluation. Urgent CT thorax should be arranged and repeated if initially unremarkable. Esophageal instrumentation should be avoided due to the risk of catastrophic air embolism or massive hemorrhage. The best way forward is emergency surgical repair; the combination which offers the best survival benefit is atrial repair combined with esophageal surgery and isolation of the esophageal aspect of the fistula.
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Fibrilación Atrial , Ablación por Catéter , Fístula Esofágica , Humanos , Masculino , Persona de Mediana Edad , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Fibrilación Atrial/complicaciones , Ablación por Catéter/efectos adversos , Fístula Esofágica/diagnóstico , Fístula Esofágica/etiología , Fístula Esofágica/cirugía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , FemeninoRESUMEN
BACKGROUND: Adverse attitudes and insufficient knowledge about organ donation after Circulatory Determined Death (DCD) among emergency staff can have important consequences for the proper identification of potential DCD donors. This is aided by the constant application of donation after Circulatory Determined Death policies, and the relative strength of support for this type of donation. Therefore, this study was conducted to investigate the awareness and attitude of emergency personnel about organ donation after Circulatory Determined Death. METHODS: This descriptive study was carried out with the participation of 49 physicians and 145 nurses working in the emergency departments of educational and medical centers of Tabriz University of Medical Sciences. Nurses were selected by simple random sampling, and all physicians working in the emergency departments were included in the study. The questionnaire of Knowledge and Attitude regarding Organ Donation after Circulatory Determined Death designed by Rodrigue et al. was used. Data were analyzed using descriptive statistics and independent samples t-test, one-way ANOVA, and chi-square test. RESULTS: Most of the nurses (62.8%) and physicians (66.7%) had a high level of knowledge about organ donation after circulatory determined death. The mean attitude score was 101.84 (SD: 9.88) out of 170 for nurses and 106.53 (SD: 11.77) for physicians. Physicians who carried organ donation cards had a more positive attitude toward organ donation after circulatory determined death. CONCLUSION: According to this study findings, knowledge and attitude of the emergency staff about organ donation was both high and positive. It is recommended to devise necessary guidelines for organ donation in Iranian emergency departments to assist in the training of colleagues in organ donation ensuring no necessary measures are missed. The results of this study would support the development of guidelines for the successful introduction of DCD in Iran.
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Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Obtención de Tejidos y Órganos , Adulto , Servicio de Urgencia en Hospital , Femenino , Humanos , Irán , Masculino , Cuerpo Médico , Persona de Mediana Edad , Adulto JovenRESUMEN
There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.
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Preservación de Órganos , Obtención de Tejidos y Órganos , Canadá , Muerte , Humanos , Perfusión , Donantes de Tejidos , Reino UnidoRESUMEN
BACKGROUND: Stroke remains a devastating complication of cardiac surgery. The aim of this study was to characterize the incidence of stroke and analyze the impact of stroke on patient outcomes and survival. METHODS: A retrospective analysis was performed of patients with a computed tomography-confirmed stroke diagnosis between 1 January 2015 and 31 March 2019 at a single center. 2:1 propensity matching was performed to identify a control population. RESULTS: Over the period 165 patients suffered a stroke (1.99%), with an incidence ranging from 0.85% for coronary artery bypass grafting to 8.14% for aortic surgery. The mean age was 70.3 years and 58.8% were male. 18% had experienced a previous stroke or transient ischemic attack. Compared to the comparison group, patients experiencing postoperative stroke had a significantly prolonged period of intensive care unit admission (8.0 vs 1.1 days P < .001) and hospital length of stay (12.94 vs 8.0 days P < .001). Patient survival was also inferior. In-hospital mortality was almost three times as high (17.0% vs 5.9%; P < .001). Longer-term survival was also inferior to Kaplan-Meier estimation (P < .001). The 1-year and 3-year survival were 61.5% and 53.8% respectively compared to 89.4% and 86.1% for the comparison group. CONCLUSION: Perioperative stroke is a devastating complication following cardiac surgery. Perioperative stroke is associated with significantly inferior outcomes in terms of both morbidity and mortality. Notably a 28% reduction in 1-year survival. Efforts should focus on identifying strategies aimed at reducing the incidence, morbidity, and mortality of perioperative stroke following cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Anciano , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Femenino , Humanos , Tiempo de Internación , Masculino , Complicaciones Posoperatorias/prevención & control , Puntaje de Propensión , Estudios Retrospectivos , Accidente Cerebrovascular/prevención & control , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.
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Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Adolescente , Adulto , Anciano , Enfermedades de los Conductos Biliares/prevención & control , Conductos Biliares/irrigación sanguínea , Niño , Muerte , Funcionamiento Retardado del Injerto/prevención & control , Circulación Extracorporea , Femenino , Supervivencia de Injerto , Humanos , Isquemia/prevención & control , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Preservación de Órganos/efectos adversos , Perfusión/métodos , Estudios Retrospectivos , Temperatura , Recolección de Tejidos y Órganos/efectos adversos , Recolección de Tejidos y Órganos/métodos , Obtención de Tejidos y Órganos/métodos , Adulto JovenRESUMEN
This is a report of a unique DCD paediatric heart transplant whereby normothermic regional perfusion was used to assess DCD heart function after death followed by ex situ heart perfusion of the graft during transportation from donor to recipient hospitals. The DCD donor was a 9-year-old boy weighing 84 kg. The recipient was 7-year-old boy with failing Fontan circulation and weighed 23 kg. It was an ABO-compatible heart transplantation. The DCD heart was reperfused and assessed using normothermic regional perfusion followed by portable ex situ heart perfusion during transportation. The orthotopic heart transplantation was successful with good graft function and no evidence of rejection on endomyocardial biopsy at 30 days post-transplant. At 1-year follow-up, excellent graft function is maintained, and he is attending school with a good quality of life. DCD heart transplantation in children is a promising solution to reducing paediatric waiting times. The case demonstrates the feasibility of using normothermic regional perfusion in the donor and ex situ heart perfusion during graft transportation. This combination allowed a functional assessment whilst minimizing warm ischaemia resulting in a successful outcome. More research and long-term follow-up are needed in order to benefit from the huge potential that paediatric DCD heart transplantation has to offer.
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Procedimiento de Fontan , Cardiopatías/cirugía , Trasplante de Corazón , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Animales , Biopsia , Bovinos , Niño , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Preservación de Órganos/métodos , Pediatría , Perfusión , Pericardio/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. METHODS: We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo. RESULTS: We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and in cells isolated from an ischemia/reperfusion Langendorff model perfused with oxygenated blood from an arrested animal but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after arrest, we tested a small-molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and postarrest outcome in vivo. CONCLUSIONS: Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which support cardiomyocyte contractility in the face of impaired postarrest myofilament calcium sensitivity. Alda-1 mitigates these effects, normalizes calcium cycling, and improves outcome.
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Aldehído Deshidrogenasa/metabolismo , Benzamidas/farmacología , Benzodioxoles/farmacología , Señalización del Calcio/efectos de los fármacos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Calcio/metabolismo , Paro Cardíaco/fisiopatología , Potenciación a Largo Plazo/efectos de los fármacos , Animales , Proteínas de Unión al Calcio/metabolismo , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Potenciación a Largo Plazo/fisiología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Retículo Sarcoplasmático/metabolismoRESUMEN
PURPOSE OF REVIEW: The aim of this study was to describe the development of a clinical programme of heart transplantation from nonheart beating (or donation after circulatory determined death, DCD) donors. DCD is an established practice in abdominal and lung transplantation. The opportunity for sufferers of advanced heart failure provided by DCD heart transplantation is described. RECENT FINDINGS: Work shows that the arrested DCD heart is viable and has a 30-min tolerance to anoxia at normal body temperature making transplantation possible. SUMMARY: The demonstration of the possibility of DCD heart transplantation and its early clinical success is described.
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Circulación Extracorporea/métodos , Trasplante de Corazón/métodos , Donantes de Tejidos/ética , Obtención de Tejidos y Órganos/métodos , Muerte Encefálica , HumanosRESUMEN
BACKGROUND: We aim to develop a rat model of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: VA-ECMO was established in twelve Male Sprague-Dawley rats (250-350 g) through cannulation of the right jugular vein for venous drainage and the right femoral artery for arterial reinfusion. Arterial blood pressure was measured using a conductance catheter through cannulation of the left carotid artery. Heart rate was monitored by electrocardiography and arterial blood gas parameters with a blood gas analyzer. The VA-ECMO circuit was tested by subjecting the rats to hypoxic cardiac arrest with resuscitation using VA-ECMO. Both load-dependent and load-independent measures of myocardial contractility were measured using pressure-volume loop analysis to confirm restoration of myocardial function post-resuscitation. RESULTS: Following hypoxic cardiac arrest VA-ECMO provided sufficient oxygenation to support the circulation. The haemodynamic and blood gas parameters were maintained at transition and during ECMO. All animals were resuscitated, regained cardiac function and were able to be weaned off ECMO post-resuscitation. CONCLUSION: We have established a safe, high-throughput, economical, functioning rat model of VA-ECMO.
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Oxigenación por Membrana Extracorpórea , Arteria Femoral/fisiopatología , Venas Yugulares/fisiopatología , Modelos Animales , Animales , Paro Cardíaco/metabolismo , Paro Cardíaco/fisiopatología , Paro Cardíaco/terapia , Hemodinámica , Hipoxia/complicaciones , Hipoxia/patología , Hipoxia/fisiopatología , Masculino , Contracción Miocárdica , Ratas , Ratas Sprague-Dawley , ResucitaciónRESUMEN
Surgery to correct a structural heart valve problem can restore sinus rhythm in approximately one-fifth of patients with atrial fibrillation (AF), and the addition of a maze procedure will increase this proportion. Evidence shows that the maze procedure may restore atrial function in some patients and may have beneficial effects on functional symptoms and prognosis. The role of the maze procedure as an isolated treatment for lone AF in the context of heart failure with no structurally correctable cause is unknown. Future progress will determine the appropriate indications for treatment and the risks and benefits of any intervention.
Asunto(s)
Fibrilación Atrial/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Atrios Cardíacos/cirugía , Sistema de Conducción Cardíaco/cirugía , Insuficiencia Cardíaca/complicaciones , Fibrilación Atrial/complicaciones , Atrios Cardíacos/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Humanos , PronósticoRESUMEN
Heart failure imposes a significant burden on all health care systems and has a 5-year mortality of 50%. Heart transplantation and ventricular assist device (VAD) implantation are the definitive therapies for end stage heart disease, although transplantation appears to offer superior long-term survival and quality of life over VAD implantation. Transplantation is limited by a shortage in donor hearts, resulting in considerable waiting list mortality. Donation after circulatory determination of death (DCD) offers a significant uplift in the number of donors for heart transplantation. The outcomes both from the UK and internationally have been exciting, with outcomes at least as good as conventional donation after brain death (DBD) transplantation. Currently, DCD hearts are reperfused using ex-situ machine perfusion (ESMP). Whilst ESMP has enabled the development of DCD transplantation, it comes at significant cost, with the per run cost of approximately GBP £90,000. In-situ perfusion of the heart, otherwise known as thoraco-abdominal normothermic regional perfusion (taNRP) is cheaper, but there are ethical concerns regarding the potential to restore cerebral perfusion in the donor. We must determine whether there is any cerebral circulation during in-situ perfusion of the heart to ensure that it does not invalidate the diagnosis of death and potentially violate the dead donor rule. Besides this, there is a need for a randomised controlled trial to definitively determine whether taNRP offers any clinical advantages over ex-situ machine perfusion. This viewpoint article explores these issues in more detail.
RESUMEN
Maximising organ utilisation from donation after circulatory death (DCD) donors could help meet some of the shortfall in organ supply, but it represents a major challenge, particularly as organ donors and transplant recipients become older and more medically complex over time. Success is dependent upon establishing common practices and accepted protocols that allow the safe sharing of DCD organs and maximise the use of the DCD donor pool. The British Transplantation Society 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated. This manuscript summarises the relevant recommendations from chapters specifically related to transplantation of cardiothoracic organs.