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1.
ASAIO J ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38531093

RESUMO

The physiologic impact of pulsatile flow (PF) on end-organ perfusion during cardiopulmonary bypass (CPB) is controversial. Using an intra-aortic balloon pump (IABP) to maintain PF during CPB for patients undergoing heart transplantation (HT) may impact end-organ perfusion, with implications for postoperative outcomes. A single-center retrospective study of 76 patients bridged to HT with IABP was conducted between January 2018 and December 2022. Beginning in May 2022, patients received IABP-generated PF during CPB at an internal rate of 80 beats/minute. Fifty-eight patients underwent HT with the IABP turned off (IABP-Off), whereas 18 patients underwent HT with IABP-generated PF (IABP-On). The unmatched IABP-On group experienced shorter organ ischemia times (180 vs. 203 minutes, p = 0.015) and CPB times (104 vs. 116 minutes, p = 0.022). The cohort was propensity matched according to age, organ ischemia time, and CPB time. Elevations in postoperative lactates in the immediate (2.8 vs. 1.5, p = 0.062) and 24 hour (4.7 vs. 2.4, p = 0.084) postoperative periods trended toward significance in the matched IABP-Off group. There was no difference in postoperative vasoactive inotropic score (VIS), postoperative creatinine, or length of stay. This limited preliminary data suggest that maintaining counterpulsation to generate PF during CPB may improve end-organ perfusion in this patient population as suggested by lower postoperative lactate levels.

2.
Clin Transplant ; 38(3): e15269, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38445531

RESUMO

INTRODUCTION: Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS: We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS: All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION: Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.


Assuntos
Benzidinas , Coração , Obtenção de Tecidos e Órgãos , Humanos , Adulto , Perfusão , Doadores de Tecidos , Morte Encefálica
3.
Clin Transplant ; 38(4): e15294, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38545881

RESUMO

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


Assuntos
Transplante de Coração , Hepatite C , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Doadores de Tecidos , Estudos Retrospectivos , Transplante de Coração/efeitos adversos , Viremia/epidemiologia , Viremia/etiologia , Seguimentos , Hepatite C/etiologia , Hepacivirus , Aloenxertos , Transplantados
4.
Ann Thorac Surg ; 117(1): 87-94, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37806334

RESUMO

BACKGROUND: The benefits of fast-track extubation in the intensive care unit (ICU) after cardiac surgery are well established. Although extubation in the operating room (OR) is safe in carefully selected patients, widespread use of this strategy in cardiac surgery remains unproven. This study was designed to evaluate perioperative outcomes with OR vs ICU extubation in patients undergoing nonemergency, isolated coronary artery bypass grafting (CABG). METHODS: The Society of Thoracic Surgeons (STS) data for all single-center patients who underwent nonemergency isolated CABG over a 6-year interval were analyzed. Perioperative morbidity and mortality with ICU vs OR extubation were compared. RESULTS: Between January 1, 2017 and December 31, 2022, 1397 patients underwent nonemergency, isolated CABG; 891 (63.8%) of these patients were extubated in the ICU, and 506 (36.2%) were extubated in the OR. Propensity matching resulted in 414 pairs. In the propensity-matched cohort, there were no differences between the 2 groups in incidence of reintubation, reoperation for bleeding, total operative time, stroke or transient ischemic attack, renal failure, or 30-day mortality. OR-extubated patients had shorter ICU hours (14 hours vs 20 hours; P < .0001), shorter postoperative hospital length of stay (3 days vs 5 days; P < .0001), a greater likelihood of being discharged directly to home (97.3% vs 89.9%; P < .0001), and a lower 30-day readmission rate (1.7% vs 4.1%; P = .04). CONCLUSIONS: Routine extubation in the OR is a feasible and safe strategy for a broad spectrum of patients after nonemergency CABG, with no increase in perioperative morbidity or mortality. Wider adoption of routine OR extubation for nonemergency CABG is indicated.


Assuntos
Extubação , Salas Cirúrgicas , Humanos , Extubação/métodos , Tempo de Internação , Estudos Retrospectivos , Ponte de Artéria Coronária
5.
Nat Med ; 29(8): 1989-1997, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37488288

RESUMO

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.


Assuntos
Anticorpos , Rejeição de Enxerto , Animais , Humanos , Suínos , Transplante Heterólogo/métodos , Xenoenxertos , Coração , Animais Geneticamente Modificados
7.
Artigo em Inglês | MEDLINE | ID: mdl-37360841

RESUMO

Background: Evidence suggests that patients critically ill with COVID-19 have a dysregulated host immune response that contributes to end-organ damage. Extracorporeal membrane oxygenation (ECMO) has been used in this population with varying degrees of success. This study was performed to evaluate the impact of ECMO on the host immunotranscriptomic response in these patients. Methods: Eleven patients critically ill with COVID-19 requiring ECMO underwent an analysis of cytokines and immunotranscriptomic pathways before ECMO (T1), after ECMO for 24 hours (T2), and 2 hours after ECMO decannulation (T3). A Multiplex Human Cytokine panel was used to identify cytokine changes, and immunotranscriptomic changes in peripheral leukocytes were evaluated by PAXgene and NanoString nCounter. Results: Differential gene expression of 11 host immune genes was noted at T2 compared with T1. The most significant genes were MD2 and MRC1, which code for binding ligands for the activation of toll-like receptors 2 and 4. Reactome analyses of differential gene expression demonstrated an impact on many of the body's most important immune inflammatory pathways. Conclusions: These findings suggest a temporal impact of ECMO on the host immunotranscriptomic response in patients critically ill with COVID-19.

8.
J Heart Lung Transplant ; 42(9): 1161-1165, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37211334

RESUMO

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.


Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Doadores de Tecidos , Preservação de Órgãos/métodos , Perfusão/métodos , Morte , Sobrevivência de Enxerto
9.
JTCVS Tech ; 17: 111-120, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36820336

RESUMO

Objective: This study aimed to evaluate the impact of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion on the metabolic milieu of donation after cardiac death organ donors before transplantation. Methods: Local donation after cardiac death donor offers are assessed for suitability and willingness to participate. Withdrawal of life-sustaining therapy is performed in the operating room. After declaration of circulatory death and a 5-minute observation period, the cardiac team performs a median sternotomy, ligation of the aortic arch vessels, and initiation of thoraco-abdominal normothermic regional perfusion via central cardiopulmonary bypass at 37 °C. Three sodium chloride zero balance ultrafiltration bags containing 50 mEq sodium bicarbonate and 0.5 g calcium carbonate are infused. Arterial blood gas measurements are obtained every 15 minutes after every zero balance ultrafiltration bag is infused, and blood is transfused as needed to maintain hemoglobin greater than 8 mg/dL. Cardiopulmonary bypass is weaned with concurrent hemodynamic and transesophageal echocardiogram evaluation of the donor heart. The remainder of the procurement, including the abdominal organs, proceeds in a similar controlled fashion as is performed for a standard donation after brain death donor. Results: Between January 2020 and May 2022, 18 donation after cardiac death transplants using the thoraco-abdominal normothermic regional perfusion protocol were performed at our institution. The median donor age was 42.5 years (range, 20-51 years), and 88.9% (16/18) were male. The mean total donor cardiopulmonary bypass time was 88.8 ± 51.8 minutes. At the beginning of cardiopulmonary bypass, the average donor lactate was 9.4 ± 1.5 mmol/L compared with an average final lactate of 5.3 ± 2.7 mmol/L (P<.0001). The average beginning potassium was 6.5 ± 1.8 mmol/L compared with an average end potassium of 4.2 ± 0.4 mmol/L (P<.0001) . The average beginning hemoglobin was 6.8 ± 0.7 g/dL, and the average end hemoglobin was 8.2 ± 1.3 g/dL (P<.001) . On average, donation after cardiac death donors received transfusions of 2.3 ± 1.5 units of packed red blood cells. Of the 18 donors who underwent normothermic regional perfusion, all hearts were deemed suitable for recovery and successfully transplanted, a yield of 100%. Other organs successfully recovered and transplanted include kidneys (80.6% yield), livers (66.7% yield), and bilateral lungs (27.8% yield). Conclusions: The use of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion is a burgeoning option for improving the quality of organs from donation after cardiac death donors. Meticulous intraoperative management of donation after cardiac death donors with a specific focus on improving their metabolic milieu may lead to improved graft function in transplant recipients.

10.
ASAIO J ; 69(3): 267-271, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36731047

RESUMO

During a 6 week period beginning early March 2020, 30 patients with severe coronavirus disease 2019 (COVID-19) were supported with venovenous extracorporeal membrane oxygenation (ECMO). This volume increase mandated rapidly training 116 nurses with no prior ECMO experience via a 2 hour crash course. A qualitative study using semistructured, in-depth interviews was conducted to evaluate the experiences of this unique nursing cohort. Fourteen registered nurses meeting inclusion criteria of no prior ECMO experience, attendance of ECMO educational crash course, direct assignment of COVID-19 patients requiring ECMO, and willingness to consent to recorded interviews participated in the study. Two semistructured interviews were conducted, audio recorded, and transcribed verbatim. Thematic analysis of the interviews was completed using Colaizzi's phenomenological method. Six themes identified were anxiety and fear of patient harm, isolation and depersonalization, value of didactic education with reinforced clinical experience, professional growth, importance of team collaboration, and pride and gratitude. Subthemes were additionally extracted. Nurses faced multiple obstacles during the pandemic. ECMO added a layer of complexity, as these patients required labor-intensive, high acuity nursing care. The impact of the pandemic and its unique challenges on nursing and medical staff warrants further investigation.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Pandemias
13.
Aorta (Stamford) ; 10(3): 104-113, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36318931

RESUMO

BACKGROUND: Coronavirus disease-19 (COVID-19) remains a public health crisis. The epidemiology of COVID-19-associated large- and medium-sized-vessel pathology is not well characterized. The aim of this study is to identify patients with possible COVID-19-associated large- and medium-sized-vessel pathology based on computed tomography (CT) imaging to provide insight into this rare, but potentially devastating, cardiovascular manifestation. METHODS: This is a single-center retrospective review of patients with CT chest, abdomen, and/or pelvis concerning for large- and medium-vessel pathology and confirmed COVID-19 infection from March 1, 2020 to October 31, 2020. RESULTS: During the study period, 6,553 CT reports were reviewed and pertinent imaging was identified in 139 patients. Of these, 8 patients (median age: 59 years, range 51-82) were COVID-19 positive. All patients had preexisting cardiovascular risk factors and three (37.5%) had an autoimmune disease. Four patients were never hospitalized for COVID-19. Among these, two presented to the hospital at a median of 39 days (range: 27-50) after their initial COVID-19 test with chest and back pain where imaging revealed extensive aortic pathology. One patient required surgical management for aortic pathology. All other patients were treated with expectant management and outpatient follow-up. CONCLUSION: The clinical and radiological presentations of COVID-19-associated large- and medium-vessel pathology are heterogeneous and can be a late finding after COVID-19 recovery. Close clinical follow-up and surveillance imaging for large- and medium-sized-vessel pathology may be warranted in COVID-19 patients.

14.
JTCVS Tech ; 16: 109-116, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36168330

RESUMO

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

16.
Chest ; 162(2): 293-294, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35940654
18.
Ann Thorac Surg ; 114(1): 70-75, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35282865

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can cause acute respiratory failure requiring mechanical ventilation. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used in patients in whom conventional mechanical ventilatory support has failed. To date, published data have focused on survival from ECMO and survival to discharge. In addition to survival to discharge, this study reports 1-year follow-up data for patients who were successfully discharged from the hospital. METHODS: A single-institution, retrospective review of all patients with severe COVID-19 who were cannulated for VV-ECMO between March 10, 2020 and May 1, 2020 was performed. A multidisciplinary ECMO team evaluated, selected, and managed patients with ECMO support. The primary outcome of this study was survival to discharge. Available 1-year follow-up data are also reported. RESULTS: A total of 30 patients were supported with VV-ECMO, and 27 patients (90%) survived to discharge. All patients were discharged home or to acute rehabilitation on room air, except for 1 patient (3.7%), who required supplemental oxygen therapy. At a median follow-up of 10.8 months (interquartile range [IQR], 8.9-14.4 months) since ECMO cannulation, survival was 86.7%, including 1 patient who underwent lung transplantation. Of the patients discharged from the hospital, 44.4% (12/27) had pulmonary function testing, with a median percent predicted forced expiratory volume of 100% (IQR, 91%-110%). For survivors, a 6-minute walk test was performed in 59.3% (16/27), with a median value of 350 m (IQR, 286-379 m). CONCLUSIONS: A well-defined patient selection and management strategy of VV-ECMO support in patients with severe COVID-19 resulted in exceptional survival to discharge that was sustained at 1-year after ECMO cannulation.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Respiração Artificial , Estudos Retrospectivos
19.
J Thorac Cardiovasc Surg ; 164(2): 557-568.e1, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34728084

RESUMO

OBJECTIVE: This pilot study sought to evaluate the feasibility of our donation after circulatory death (DCD) heart transplantation protocol using cardiopulmonary bypass (CPB) for normothermic regional reperfusion (NRP). METHODS: Suitable local DCD candidates were transferred to our institution. Life support was withdrawn in the operating room (OR). On declaration of circulatory death, sternotomy was performed, and the aortic arch vessels were ligated. CPB was initiated with left ventricular venting. The heart was reperfused, with correction of any metabolic abnormalities. CPB was weaned, and cardiac function was assessed at 30-minute intervals. If accepted, the heart was procured with cold preservation and transplanted into recipients in a nearby OR. RESULTS: Between January 2020 and January 2021, a total of 8 DCD heart transplants were performed: 6 isolated hearts, 1 heart-lung, and 1 combined heart and kidney. All donor hearts were successfully resuscitated and weaned from CPB without inotropic support. Average lactate and potassium levels decreased from 9.39 ± 1.47 mmol/L to 7.20 ± 0.13 mmol/L and 7.49 ± 1.32 mmol/L to 4.36 ± 0.67 mmol/L, respectively. Post-transplantation, the heart-lung transplant recipient required venoarterial extracorporeal membrane oxygenation for primary lung graft dysfunction but was decannulated on postoperative day 3 and recovered uneventfully. All other recipients required minimal inotropic support without mechanical circulatory support. Survival was 100% with a median follow-up of 304 days (interquartile range, 105-371 days). CONCLUSIONS: DCD heart transplantation outcomes have been excellent. Our DCD protocol is adoptable for more widespread use and will increase donor heart availability in the United States.


Assuntos
Transplante de Coração , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Coração , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Preservação de Órgãos/métodos , Perfusão , Projetos Piloto , Doadores de Tecidos , Estados Unidos
20.
ASAIO J ; 68(5): 714-720, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380951

RESUMO

Intra-aortic balloon pumps (IABPs) can be used to provide hemodynamic support in patients with end-stage heart failure as a bridge to transplantation (BTT). The IABP is commonly inserted via the common femoral artery, which can limit patients' mobility. The Ramsey protocol, developed by a critical care physical therapist, allows patients with femoral IABPs to ambulate with the assistance of a tilt table. The aim of this study was to determine the safety and feasibility of a modified Ramsey protocol for early mobilization of patients with femoral IABPs as BTT. This is a retrospective single-center review of patients with femoral IABPs as BTT using a tilt table protocol from May 2019 to May 2020. Primary outcomes were time to successful ambulation, number of successful ambulation events, and ambulation-associated adverse events, including IABP augmentation, waveform, positioning changes, and vascular complications at the insertion site. Twenty-four patients (mean age 55 ± 16 years) underwent femoral IABP insertion as BTT and were mobilized following our protocol. Nineteen patients (79.2%) successfully ambulated with a median of three sessions (interquartile range, 2-4) per patient. The median time from IABP insertion to ambulation was 3 days (interquartile range, 2-5). Twenty-one patients underwent heart transplantation, of which all 19 who ambulated were successfully bridged to transplantation. Early mobilization in select patients with femoral IABPs can be performed safely and successfully, avoiding the deleterious effects of bed rest that have been historically seen in this patient population.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Adulto , Idoso , Deambulação Precoce , Estudos de Viabilidade , Artéria Femoral/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Balão Intra-Aórtico/efeitos adversos , Balão Intra-Aórtico/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos
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