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INTRODUCTION: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. METHODS: Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). RESULTS: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. CONCLUSION: Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.
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Animais Geneticamente Modificados , Transplante de Coração , Inflamação , Papio , Transplante Heterólogo , Animais , Transplante Heterólogo/métodos , Transplante de Coração/métodos , Suínos , Inflamação/imunologia , Coagulação Sanguínea/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Xenoenxertos/imunologia , Galactosiltransferases/genética , Imunossupressores/farmacologia , Citocinas/metabolismoRESUMO
Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.
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Procedimentos Cirúrgicos Cardíacos , Fibrinolíticos , Sistema de Registros , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Cuidados Intraoperatórios/métodos , Ponte Cardiopulmonar/métodos , Perda Sanguínea Cirúrgica/prevenção & controleRESUMO
This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation.
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Sobrevivência de Enxerto , Transplante de Coração , Xenoenxertos , Imunossupressores , Transplante Heterólogo , Animais , Transplante de Coração/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Resultado do Tratamento , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Animais Geneticamente Modificados , Fatores de Risco , Alemanha , Suínos , Seleção de PacientesRESUMO
BACKGROUND: The benefits of minimally invasive techniques in cardiac surgery remain poorly defined. We evaluated the short- and mid-term outcomes after surgical aortic valve replacement through partial upper versus complete median sternotomy (MS) in a large, German multicenter cohort. METHODS: A total of 2,929 patients underwent isolated surgical aortic valve replacement via partial upper sternotomy (PUS, n = 1,764) or MS (n = 1,165) at nine participating heart centers between 2016 and 2020. After propensity-score matching, 1,990 patients were eligible for analysis. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke at 30 days and in follow-up, up to 5 years. Secondary end points were acute kidney injury, length of hospital stay, transfusions, deep sternal wound infection, Dressler's syndrome, rehospitalization, and conversion to sternotomy. RESULTS: Unadjusted MACCE rates were significantly lower in the PUS group both at 30 days (p = 0.02) and in 5-year follow-up (p = 0.01). However, after propensity-score matching, differences between the groups were no more statistically significant: MACCE rates were 3.9% (PUS) versus 5.4% (MS, p = 0.14) at 30 days, and 9.9 versus 11.3% in 5-year follow-up (p = 0.36). In the minimally invasive group, length of intensive care unit (ICU) stay was shorter (p = 0.03), Dressler's syndrome occurred less frequently (p = 0.006), and the rate of rehospitalization was reduced significantly (p < 0.001). There were 3.8% conversions to full sternotomy. CONCLUSION: In a large, German multicenter cohort, MACCE rates were comparable in surgical aortic valve replacement through partial upper and complete sternotomies. Shorter ICU stay and lower rates of Dressler's syndrome and rehospitalization were in favor of the partial sternotomy group.
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Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.
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Doenças Cardiovasculares , Fibrinolíticos , Humanos , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversosRESUMO
AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.
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Aspirina/uso terapêutico , Ponte de Artéria Coronária/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/epidemiologia , Resultado do TratamentoRESUMO
Aims: Antegrade-transseptal approach to treat left ventricular tachyarrhythmia (LVT) is useful and widespread. Meanwhile, Mitraclip has been recently introduced as an alternative to mitral valve surgery for severe mitral regurgitation, usually coexisting with ventricular arrhythmias. However, data on the antegrade approach for mapping and ablating LVT in these patients are insufficient. We evaluated the feasibility and clinical impact of the antegrade approach for LVT after Mitraclip implantation. Methods and results: We included five patients (all men; age 72.6 ± 10.5 years) with Mitraclip implantation who underwent catheter ablation for LVT and employed the antegrade approach. Post-ablation mitral valve function was systematically evaluated by transthoracic echocardiography. Six procedures with the antegrade approach were performed on the five patients; three of these patients developed electrical storm. The number of implanted Mitraclip was 1 in two patients, 2 in two patients, and 3 in one patient, for a mean duration of 417 ± 324 days before ablation. After 117-day median follow-up, there was no recurrence of electrical storm, but ventricular tachyarrhythmia recurred and required implantable cardioverter defibrillator therapy in one patient (only sporadic anti-tachycardia pacing); two patients died because of reasons other than ventricular arrhythmia. There was no procedure-related injury on the mitral valve immediately and 3 months after ablation. Conclusions: Antegrade ablation of LVT after Mitraclip implantation may be feasible. Non-arrhythmic death during follow-up suggested the need for comprehensive evaluation before and after ablation.
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Septo Interatrial , Ablação por Cateter/métodos , Anuloplastia da Valva Mitral/instrumentação , Insuficiência da Valva Mitral/cirurgia , Taquicardia Ventricular/cirurgia , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/cirurgia , Desfibriladores Implantáveis , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Instrumentos Cirúrgicos , Taquicardia Ventricular/complicações , Resultado do TratamentoRESUMO
BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS: Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN: The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY: There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.
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Adenosina/análogos & derivados , Aspirina/uso terapêutico , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Adenosina/uso terapêutico , Idoso , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Ticagrelor , Resultado do TratamentoRESUMO
BACKGROUND: As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient's native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. METHODS: Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/± thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. RESULTS: In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed pre-clinical suspicion of humoral rejection, which was not inhibited by the extended conventional IS including intensified treatments, and signs of thrombotic microangiopathy. Grafts of group 2 presented with only mild-to-moderate features of humoral rejection and thrombotic microangiopathy, except in one case of delayed rejection on day 17. The other experiments in this group were terminated because of untreatable pulmonary oedema, recurring ventricular fibrillation, Aspergillus sepsis, as well as a combination of a large donor organ and late toxic side effects due to TLI. CONCLUSIONS: Longer-term results were difficult to achieve in this model due to the IS regimens used. However, we conclude that heterotopic intrathoracic heart transplantation may be an option for clinical xenotransplantation.
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Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Transplante de Coração , Imunossupressores/farmacologia , Animais , Animais Geneticamente Modificados , Anticorpos/imunologia , Anticorpos/farmacologia , Transplante de Coração/métodos , Suínos , Transplante Heterólogo/métodosRESUMO
Topical hemostatic agents that can seal tissues and assist in the coagulation cascade of patients undergoing surgery have been readily available for several decades. Using either synthetic or animal/plant-derived materials, these agents represent a powerful tool to reduce postoperative bleeding complications in cases where mechanical or energy-driven hemostasis is not possible or insufficient. Recently, a novel sealing hemostatic patch, HEMOPATCH (Baxter International, Deerfield, IL), was developed. The device is a thin and flexible patch consisting of a specifically-formulated porous collagen matrix, coated on one side with a thin protein-binding layer. This gives the patch a dual mechanism of action, in which the two components interact to achieve hemostasis by sealing off the bleeding surface and initiating the body's own clotting mechanisms. Here we present a series of case reports that outline the quick, effective hemostatic sealing of HEMOPATCH in a variety of clinical applications, including solid organ, gastrointestinal, biliopancreatic, endocrine, cardiovascular, and urologic surgeries. Essentially a feasibility study, these reports demonstrate how HEMOPATCH can be applied to seal almost any bleeding surface encountered during a range of procedures. Our results show that the device is eminently capable in both via laparotomy and laparoscopic approaches, and in patients with impaired coagulation or highly variable anatomies. In conclusion, our cases document the ease-of-use, application, and immediate hemostatic effect of the patch across a broad range of surgical settings and paves the way for future randomized clinical trials with more extensive follow-up.
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Transplantation of genetically modified porcine hearts and kidneys could become a solution to the persistent shortage of human organ donors. Progress has been made in genetic engineering of donor pigs, preservation techniques after organ harvesting and immunosuppression using co-stimulation blockade with anti-CD40/CD40L monoclonal antibodies. Progress has also been made in in the development of methods that detect pathogenic porcine viruses and prevent their transmission to the recipient. As normal land breed pig organs continue to grow in the recipient to their original size, different pig breeds (such as Auckland Island pigs) are now used which reach a final size suitable for humans. Alternatively, a knock-out of the growth hormone receptor gene has been established, e.g., in the 10GM genetically modified pigs from Revivicor/United Therapeutics, USA. The first clinical pilot studies including patients suffering from terminal heart failure are expected to start in Germany in about 2 years.
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Transplante Heterólogo , Animais , Humanos , Suínos , Transplante Heterólogo/métodos , Animais Geneticamente Modificados , Transplante de Coração/métodos , Transplante de Rim/métodosRESUMO
Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface-the endothelial glycocalyx-are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.
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OBJECTIVES: There is an ongoing discussion if valve-in-valve implantations into failing mitral xenografts should be performed only via a transapical approach. BACKGROUND: In selected high-risk patients, transcatheter valve implantation is an emerging therapy for degenerated mitral xenografts in need of repeated valve replacement. METHODS: Here we describe three different strategies to treat a failing mitral biological prosthesis (Carpentier Edwards S.A.V) by implantation of a SAPIEN-XT valve, which was performed in three different patients. As access site, a transjugular/transseptal approach, a transfemoral/transseptal approach, and a transapical approach were chosen. RESULTS: With all three approaches, valve-in-valve implantation was successfully achieved. The acute hemodynamic effects were excellent and according to VARC there was no adverse event recorded during a 6 months follow-up. CONCLUSIONS: Feasibility of all three approaches is demonstrated and might be taken into consideration for treatment in various patients.
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Bioprótese , Cateterismo Cardíaco/instrumentação , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/terapia , Valva Mitral/cirurgia , Falha de Prótese , Idoso de 80 Anos ou mais , Valvuloplastia com Balão , Feminino , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Desenho de Prótese , Resultado do TratamentoRESUMO
PURPOSE: To analyse the outcome of coronary artery bypass grafting (CABG) in octogenarians with coronary multivessel disease and the impact of different graft strategies and other factors. METHODS: Out of 1654 patients with multivessel disease who underwent CABG at our institution between January 2014 and March 2020, we investigated 225 consecutive patients with a median age of 82.1 years for survival prediction and need for coronary reintervention; a detailed outcome analysis was performed. RESULTS: At mean follow-up of 3.3 years, the overall survival was 76.4%. An indication for emergency operation (p = 0.002), age (p <0.001), chronic pulmonary disease (p = 0.024), and reduced renal or ventricular function (p <0.001) had the highest impact on limited survival. The combination outcome of survival and coronary reintervention was 1.7-fold improved (p = 0.024) after use of the bilateral internal thoracic artery (BITA) (66.2%). Off-pump CABG (12%) revealed no impact on survival. Smokers showed a poorer outcome (p = 0.004). The logistic European System for Cardiac Operative Risk Evaluation was highly effective for evaluating long-term outcomes (p <0.001). CONCLUSIONS: BITA grafting normalizes survival and reveals a better outcome in octogenarians with multivessel disease. However, patients at risk of poorer survival were operated under emergency conditions and those with pulmonary disease and reduced ventricular or renal function.
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Objectives: Patients on ticagrelor undergoing urgent cardiac surgery are at high risk for perioperative bleeding complications. We sought to determine whether intraoperative hemoadsorption could remove ticagrelor and lower circulating drug concentrations. Methods: The hemoadsorption device was incorporated in the cardiopulmonary bypass (CPB) circuit and remained active for the duration of the pump run. Blood samples were collected before and after CPB. The main objective of the current analysis was to compare mean total plasma ticagrelor levels (ng/mL) at baseline with ticagrelor levels obtained at the end of CPB. Plasma ticagrelor levels were measured at a certified outside laboratory (LabConnect). Data are presented as mean ± standard deviation. Results: A total of 11 patients undergoing urgent coronary artery bypass grafting at 3 institutions were included (mean age, 67.9 ± 9.9 years; 91% male; mean European System for Cardiac Operative Risk Evaluation II of 3.0 ± 3.3%; range, 0.7%-12.4%). Mean intraoperative hemoadsorption duration was 97.1 ± 43.4 minutes with a mean flow rate through the device of 422.9 ± 40.3 mL/min. Mean ticagrelor levels pre-CPB were 103.5 ± 63.8 ng/mL compared with mean post-CPB levels of 34.0 ± 17.5 ng/mL, representing a significant 67.1% reduction (P < .001). Intraoperative integration of the device was simple and safe without any device-related adverse events reported. Conclusions: This is the first in vivo report demonstrating that intraoperative hemoadsorption can efficiently remove ticagrelor and significantly reduce circulating drug levels. Whether active ticagrelor removal can reduce serious perioperative bleeding in patients undergoing urgent cardiac surgery is currently being evaluated in the double-blinded, randomized Safe and Timely Antithrombotic Removal-Ticagrelor (STAR-T) trial.
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OBJECTIVE: To analyze the results of hemoadsorption in patients with cardiac surgery to thoracic aortic surgery, who had been loaded beforehand with either Factor Xa inhibitor rivaroxaban or P2Y12 receptor antagonist ticagrelor. METHODS: We investigated 21 of 171 consecutive patients (median age 71 [interquartile range 62, 76] years) who underwent emergency cardiac operations for acute type A aortic dissection between 2014 and 2020. These patients were pretreated with rivaroxaban (n = 9) or ticagrelor (n = 12). In ten of 21 cases (since 2017), we installed a hemoadsorber into the heart-lung machine and compared the results to eleven patients done without hemoadsorber before that time. RESULTS: The operation time was significantly shorter in the adsorber group (286 ± 40 min vs. 348 ± 79 min; p = 0.045). The postoperative 24-hour drainage volume was significantly lower after adsorption (p <0.001; 482 ± 122 ml vs. 907 ± 427 ml) and no rethoracotomy had to be performed (compared to two rethoracotomies [18.9%] among patients without adsorber use). Also, patients without hemoadsorption required significantly more platelet transfusions (p = 0.049). CONCLUSIONS: In patients with acute type A aortic dissection who were pretreated with rivaroxaban and ticagrelor, the intraoperative use of CytoSorb hemoadsorption during cardiopulmonary bypass is reported for the first time. The method was found to be effective to prevent from bleeding and to improve the outcome in aortic dissection.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Procedimentos Cirúrgicos Cardíacos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Rivaroxabana/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia; the lifetime risk for a 55-year-old person to develop atrial fibrillation is 37%. In recent years, years there have been various distinct changes in the clinical management of AF. METHODS: This review is based on a selective search for literature on the treatment of AF and the prevention of thromboembolic complications. The updated guideline of the European Society of Cardiology (ESC) for the diagnosis and treatment of AF was also taken into consideration. RESULTS: The main components of AF management are the comprehensive treatment of risk factors and concomitant diseases, as well as the prevention of thromboembolic complications, usually with non-vitamin-K-dependent oral anticoagulants or vitamin K antagonists, according to individual risk stratification. Beyond this, either rate or rhythm control are viable treatment concepts. Symptomatic patients in whom reversible causes have been ruled out should be offered rhythm-control therapy early in their course. In patients with risk factors and/or heart failure, an early rhythm control strategy has been found to be beneficial. As antiarrhythmic drugs often prove to be ineffective over the long term, catheter ablation is now becoming increasingly important in AF management. CONCLUSION: The clinical management of atrial fibrillation consists of a multimodal approach with risk stratification, lifestyle modification, prevention of thromboembolism, and, if possible, early rhythm control therapy.
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Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower.
RESUMO
Background: Antithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications. Methods: As a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement. Results: From all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization. Discussion: Bleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review.