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INTRODUCTION: A well-known complication of veno-arterial extracorporeal membrane oxygenation (VA ECMO) is differential hypoxia, in which poorly-oxygenated blood ejected from the left ventricle mixes with and displaces well-oxygenated blood from the circuit, thereby causing cerebral hypoxia and ischemia. We sought to characterize the impact of patient size and anatomy on cerebral perfusion under a range of different VA ECMO flow conditions. METHODS: We use one-dimensional (1D) flow simulations to investigate mixing zone location and cerebral perfusion across 10 different levels of VA ECMO support in eight semi-idealized patient geometries, for a total of 80 scenarios. Measured outcomes included mixing zone location and cerebral blood flow (CBF). RESULTS: Depending on patient anatomy, we found that a VA ECMO support ranging between 67-97% of a patient's ideal cardiac output was needed to perfuse the brain. In some cases, VA ECMO flows exceeding 90% of the patient's ideal cardiac output are needed for adequate cerebral perfusion. CONCLUSIONS: Individual patient anatomy markedly affects mixing zone location and cerebral perfusion in VA ECMO. Future fluid simulations of VA ECMO physiology should incorporate varied patient sizes and geometries in order to best provide insights toward reducing neurologic injury and improved outcomes in this patient population.
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BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.
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Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca , Humanos , Administração por Inalação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Epoprostenol/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Óxido Nítrico , VasodilatadoresRESUMO
BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).
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Morte Encefálica , Transplante de Coração , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Sobrevivência de Enxerto , Preservação de Órgãos , Doadores de Tecidos , Morte , Segurança do PacienteRESUMO
BACKGROUND: Heart transplantation (HT) has historically been limited by organ availability. Use of donation after circulatory death (DCD) donors addresses this limitation by utilizing previously unused hearts through use of the Organ Care System (OCS). OBJECTIVES: This study aimed to determine the impact of procurement and transportation method on allograft structure and function using early post-transplant cardiac magnetic resonance imaging (MRI). METHODS: Patients who underwent HT at our institution from February 1, 2020, through April 30, 2021 who underwent cardiac MRI imaging <60 days from transplant were included. Recipient and donor characteristics, clinical outcomes, and MRI findings were compared between those who underwent DCD transplantation using the OCS device (DCD-OCS), brain dead donation (DBD) using the OCS device (DBD-OCS), and DBD transported via cold storage (DBD-cold storage) using one-way analysis of variance. RESULTS: A total of 85 patients underwent HT with a cardiac MRI during the study period. Thirty-one (36%) patients received a DCD organ, 16 (19%) received a DBD-OCS organ and 38 (45%) received a DBD-cold storage organ. Rates of primary graft dysfunction (PGD) were significantly higher in DCD transplants (19.5% DCD vs. .0% DBD-OCS and 5.3% DBD-cold storage; p < .050 across three groups), but with no differences in mortality or rejection. There were no differences in cardiac MRI findings between the three transplant types, including presence of gadolinium hyperenhancement after transplant (all p > .050). CONCLUSIONS: We observed no differences in early cardiac MRI findings between patients that received DCD and DBD-OCS heart transplants compared with those receiving DBD-cold storage transplants.
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Transplante de Coração , Obtenção de Tecidos e Órgãos , Humanos , Doadores de Tecidos , Morte Encefálica , Imageamento por Ressonância Magnética , Sobrevivência de Enxerto , Estudos Retrospectivos , MorteRESUMO
BACKGROUND: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation. METHODS AND RESULTS: Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021. PGD was diagnosed within 24 hours after transplant according to modified International Society for Heart and Lung Transplant criteria. A total of 459 patients underwent isolated heart transplantation during the study period, 65 (14%) following DCD and 394 (86%) following DBD. The incidence of moderate or severe PGD in DCD and DBD recipients was 34% and 23%, respectively (Pâ¯=â¯0.070). DCD recipients were more likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; Pâ¯=â¯0.004). Among patients with severe PGD, DCD recipients experienced shorter median (Q1, Q3) duration of post-transplant mechanical circulatory support (6 [4, 7] vs 9 [5, 14] days; Pâ¯=â¯0.039), shorter median post-transplant hospital length of stay (17 [15, 29] vs 52 [26, 83] days; Pâ¯=â¯0.004), and similar 60-day survival rates (100% [95% CI: 76.8%-100%] vs 80.0% [63.1%-91.6%]; Pâ¯=â¯0.17) and overall survival (log-rank; Pâ¯=â¯0.078) compared with DBD recipients. CONCLUSIONS: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, DCD recipients with severe PGD spent fewer days on mechanical circulatory support and in the hospital than similar DBD patients. These findings suggest that patterns of graft dysfunction and recovery may differ between donor types, and they support the expansion of the heart-donor pool with DCD.
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Insuficiência Cardíaca , Transplante de Coração , Disfunção Primária do Enxerto , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Morte Encefálica , Estudos Retrospectivos , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Doadores de Tecidos , Transplante de Coração/efeitos adversos , Sobrevivência de EnxertoRESUMO
Advanced heart failure affects more than 250,000 people in the United States alone and is associated with high risk of morbidity and mortality. Cardiac transplantation provides a cure for patients with advanced disease but has historically been limited by donor availability. Recent changes in the allocation system as well as advances in donor selection, procurement and desensitization protocols have served to widen the donor pool and increase the availability of cardiac transplantation for those in need. This review provides an update on recent advances in cardiac transplantation.
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Insuficiência Cardíaca , Transplante de Coração , Humanos , Estados Unidos , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Doadores de TecidosRESUMO
BACKGROUND: Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes. METHODS: We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality. RESULTS: Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28). CONCLUSION: In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation.
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Parada Cardíaca , Transplante de Rim , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Feminino , Adolescente , Masculino , Morte Encefálica , Sobrevivência de Enxerto , Doadores de Tecidos , Estudos Retrospectivos , MorteRESUMO
Heart Donation after Circulatory Death (DCD) has the potential to significantly increase the number of patients benefitting from heart transplantation. However, the expansion of DCD heart transplantation is currently limited by unanswered questions pertaining to best practices in DCD heart procurement. Additionally, significant variability exists within regulatory frameworks, professional guidelines, and published practices of DCD procurement processes. Here we describe the current practice and outstanding questions related to fundamental aspects of DCD heart procurement, including donor selection, premortem donor intervention, ischemic definitions, confirmation of circulatory death, and techniques for heart procurement and preservation. Addressing these key issues through research and consensus recommendations will facilitate the advancement of the field and ultimately expand the opportunity for heart transplantation to a greater number of patients.
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Transplante de Coração , Obtenção de Tecidos e Órgãos , Morte , Seleção do Doador , Transplante de Coração/métodos , Humanos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de TecidosRESUMO
We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.
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COVID-19 , Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/métodos , Doadores de TecidosRESUMO
Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.
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Transplante de Coração , Aloenxertos , Animais , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Coração/métodos , Humanos , Suínos , Doadores de Tecidos , Transplante HeterotópicoRESUMO
OBJECTIVES: Right heart failure remains a serious complication of left ventricular assist device therapy. Many patients presenting for left ventricular assist device implantation have significant tricuspid regurgitation. It remains unknown whether concurrent tricuspid valve surgery reduces postoperative right heart failure. The primary aim was to identify whether concurrent tricuspid valve surgery reduced the incidence of moderate or severe right heart failure within the first 6 months after left ventricular assist device implantation. METHODS: Patients with moderate or severe tricuspid regurgitation on preoperative echocardiography were randomized to left ventricular assist device implantation alone (no tricuspid valve surgery) or with concurrent tricuspid valve surgery. Randomization was stratified by preoperative right ventricular dysfunction. The primary end point was the frequency of moderate or severe right heart failure within 6 months after surgery. RESULTS: This report describes a planned interim analysis of the first 60 randomized patients. The tricuspid valve surgery group (n = 32) had mild or no tricuspid regurgitation more frequently on follow-up echocardiography studies compared with the no tricuspid valve surgery group (n = 28). However, at 6 months, the incidence of moderate and severe right heart failure was similar in each group (tricuspid valve surgery: 46.9% vs no tricuspid valve surgery: 50%, P = .81). There was no significant difference in postoperative mortality or requirement for right ventricular assist device between the groups. There were also no significant differences in secondary end points of functional status and adverse events. CONCLUSIONS: The presence of significant tricuspid regurgitation before left ventricular assist device is associated with a high incidence of right heart failure within the first 6 months after surgery. Tricuspid valve surgery was successful in reducing postimplant tricuspid regurgitation compared with no tricuspid valve surgery but was not associated with a lower incidence of right heart failure.
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OBJECTIVE: To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support. METHODS: A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality. RESULTS: Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46). CONCLUSIONS: In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19.
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COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Adolescente , Adulto , COVID-19/terapia , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We assessed the effect of implementing a protocol-directed strategy to determine when patients can be liberated from venovenous extracorporeal membrane oxygenation on extracorporeal membrane oxygenation duration, time to initiation of first sweep-off trial, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and survival to hospital discharge. DESIGN: Single-center retrospective before and after study. SETTING: The medical ICU at an academic medical center. PATIENTS: One-hundred eighty patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at a single institution from 2013 to 2019. INTERVENTIONS: In 2016, our institution implemented a daily assessment of readiness for a trial off extracorporeal membrane oxygenation sweep gas ("sweep-off trial"). When patients met prespecified criteria, the respiratory therapist performed a sweep-off trial to determine readiness for discontinuation of venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients were treated before implementation of the sweep-off trial protocol, and 113 patients were treated after implementation. Patients managed using the sweep-off trial protocol had a significantly shorter extracorporeal membrane oxygenation duration (5.5 d [3-11 d] vs 11 d [7-15.5 d]; p < 0.001), time to first sweep-off trial (2.5 d [1-5 d] vs 7.0 d [5-11 d]; p < 0.001), duration of mechanical ventilation (15.0 d [9-31 d] vs 25 d [21-33 d]; p = 0.017), and ICU length of stay (18 d [10-33 d] vs 27.0 d [21-36 d]; p = 0.008). There were no observed differences in hospital length of stay or survival to hospital discharge. CONCLUSIONS: In patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at our institution, implementation of a daily, respiratory therapist assessment of readiness for a sweep-off trial was associated with a shorter time to first sweep-off trial and shorter duration of extracorporeal membrane oxygenation. Among survivors, the postassessment group had a reduced duration of mechanical ventilation and ICU lengths of stay. There were no observed differences in hospital length of stay or inhospital mortality.
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The recently concluded prospective Portable Organ Care System (OCS) Heart trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System Heart for Preserving and Assessing Expanded Criteria Donor Hearts for Transplantation (EXPAND) demonstrated that the use of ex vivo perfusion for expanded-criteria hearts may be a viable method for increasing the use of donor hearts. We sought to estimate the potential impact of ex vivo expanded-criteria heart perfusion on the donor pool in the United States by using a large national transplant registry. After applying the inclusion criteria of EXPAND, 8637 potentially eligible donors were identified in the U.S. between January 1, 2015, and June 30, 2019, representing a substantial potential increase in the donor pool.