RESUMO
Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.
Assuntos
Isquemia Miocárdica , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Volume Sistólico , Função Ventricular Esquerda , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Coração , Resultado do Tratamento , Isquemia Miocárdica/terapiaRESUMO
Background. Surgery for acute type A aortic dissection confers a risk for significant bleeding. We analyzed the impact of massive bleeding on complications after surgery for acute type A aortic dissection. Methods. Patients undergoing surgery for acute type A aortic dissection from the retrospective multicenter Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database 2005-2014 were eligible. Massive bleeding was defined according to the Universal Definition of Perioperative Bleeding. The primary outcome measure was early mortality and secondary outcome measures were perioperative stroke, mechanical ventilation more than 48 h, new-onset dialysis, and intensive care unit stay. Propensity score matching was performed to adjust for differences in covariates. Results. Nine hundred ninety-seven patients were included, of whom 403 (40.4%) had massive bleeding. In the propensity score-matched cohort (344 pairs), patients with massive bleeding had higher 30-day mortality (17.2 versus 7.6%, p < .001), mechanical ventilation more than 48 h (52.8 versus 22.6%, p < .001), perioperative stroke (24.3 versus 14.8%, p = .002), new-onset dialysis (22.5 versus 4.9%, p < .001), and longer intensive care unit stay (6 versus 3 days, p < .001), compared with patients without massive bleeding. Risk factors for massive bleeding were previous cardiac surgery, preoperative clopidogrel or ticagrelor therapy, DeBakey type I dissection, and localized or generalized malperfusion. Conclusions. Massive bleeding in surgery for acute type A aortic dissection is associated with a markedly increased risk for severe complications as well as early death. Further improvement of surgical technique and pharmacological optimization of coagulation is paramount to possibly improve outcomes in acute type A aortic dissection repair.
Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Bases de Dados Factuais , Hemorragia Pós-Operatória , Respiração Artificial , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Resultado do Tratamento , Fatores de Tempo , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/complicações , Medição de Risco , Hemorragia Pós-Operatória/mortalidade , Hemorragia Pós-Operatória/etiologia , Doença Aguda , Países Escandinavos e Nórdicos/epidemiologia , Tempo de Internação , Diálise Renal , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: Cardiopulmonary bypass (CPB) ensures tissue oxygenation during cardiac surgery. New technology allows continuous registration of CPB variables during the operation. The aim of the present investigation was to study the association between CPB management and the risk of postoperative acute kidney injury (AKI). METHODS: This observational study based on prospectively registered data included 2661 coronary artery bypass grafting and/or valve patients operated during 2016-2020. Individual patient characteristics and postoperative outcomes collected from the SWEDEHEART registry were merged with CPB variables automatically registered every 20 s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics. RESULTS: In total, 387 patients (14.5%) developed postoperative AKI. After adjustments, longer time on CPB and aortic cross-clamp, periods of compromised blood flow during aortic cross-clamp time, and lower nadir hematocrit were associated with the risk of AKI, while mean blood flow, bladder temperature, central venous pressure, and mixed venous oxygen saturation were not. Patient characteristics independently associated with AKI were advanced age, higher body mass index, hypertension, diabetes mellitus, atrial fibrillation, lower left ventricular ejection fraction, estimated glomerular filtration rate <60 or >90 mL/min/m2 , and preoperative hemoglobin concentration below or above the normal sex-specific range. CONCLUSIONS: To reduce the risk of AKI after cardiac surgery, aortic clamp time and CPB time should be kept short, and low hematocrit and periods of compromised blood flow during aortic cross-clamp time should be avoided if possible.
Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Feminino , Masculino , Humanos , Ponte Cardiopulmonar/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/epidemiologiaRESUMO
AIMS: An observational nationwide all-comers prospective register study to analyse outcomes after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in unprotected left main coronary artery (LMCA) disease. METHODS AND RESULTS: All patients undergoing coronary angiography in Sweden are registered in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. Between 01/01/2005 and 12/31/2015, 11 137 patients with LMCA disease underwent CABG (n = 9364) or PCI (n = 1773). Patients with previous CABG, ST-elevation myocardial infarction (MI) or cardiac shock were excluded. Death, MI, stroke, and new revascularization during follow-up until 12/31/2015 were identified using national registries. Cox regression with inverse probability weighting (IPW) and an instrumental variable (IV), administrative region, were used. Patients undergoing PCI were older, had higher prevalence of comorbidity but lower prevalence of three-vessel disease. PCI patients had higher mortality than CABG patients after adjustments for known cofounders with IPW analysis (hazard ratio [HR] 2.0 [95% confidence interval (CI) 1.5-2.7]) and known/unknown confounders with IV analysis (HR 1.5 [95% CI 1.1-2.0]). PCI was associated with higher incidence of major adverse cardiovascular and cerebrovascular events (MACCE; death, MI, stroke, or new revascularization) than CABG, with IV analysis (HR 2.8 [95% CI 1.8-4.5]). There was a quantitative interaction for diabetic status regarding mortality (P = 0.014) translating into 3.6 years (95% CI 3.3-4.0) longer median survival time favouring CABG in patients with diabetes. CONCLUSION: In this non-randomized study, CABG in patients with LMCA disease was associated with lower mortality and fewer MACCE compared to PCI after multivariable adjustment for known and unknown confounders.
Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Ponte de Artéria Coronária/métodos , Diabetes Mellitus/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Sistema de RegistrosRESUMO
INTRODUCTION: One of the most serious complications of surgical aortic valve replacement (SAVR) is stroke that can result in increased rates of complications, morbidity and mortality postoperatively. The aim of this study was to investigate incidence, risk factors and short-term outcome in a well defined cohort of SAVR-patients. MATERIALS AND METHOD: A retrospective study on 740 consecutive aortic stenosis patients who underwent SAVR in Iceland 2002-2019. Patients with stroke were compared with non-stroke patients; including preoperative risk factors of cardiovascular disease, echocardiogram-results, rate of early postoperative complications other than stroke and 30 day mortality. RESULTS: Mean age was 71 yrs (34% females) with 57% of the patients receiving stented bioprosthesis, 31% a stentless Freestyle®-valve and 12% a mechanical valve. Mean EuroSCORE-II was 3.6, with a maximum preop-gradient of 70 mmHg and an estimated valvular area of 0.73 cm2. Thirteen (1.8%) patients were diagnosed with stroke where hemiplegia (n=9), loss of consciousness (n=3) and/or aphasia (n=4) were the most common presenting symptoms. In 70% of cases the neurological symptoms resolved or disappeared in the first weeks and months after surgery. Only one patient out of 13 died within 30-days (7.7%). Stroke-patients had significantly lower BMI than non-stroke patients, but other risk factors of cardiovascular diseases, intraoperative factors or the rate of other severe postoperative complications than stroke were similar between groups. Total length of stay was 14 days vs. 10 days median, including 2 vs. 1 days in the ICU, in the stroke and non-stroke-groups, respectively. CONCLUSIONS: The rate of stroke after SAVR was low (1.8%) and in line with other similar studies. Although a severe complication, most patients with perioperative stroke survived 30 days postoperatively and in majority of cases neurological symptoms recovered.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Acidente Vascular Cerebral , Humanos , Feminino , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/diagnóstico por imagem , Masculino , Idoso , Fatores de Risco , Estudos Retrospectivos , Islândia/epidemiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Implante de Prótese de Valva Cardíaca/instrumentação , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/etiologia , Incidência , Fatores de Tempo , Resultado do Tratamento , Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Medição de Risco , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The aims of this retrospective study were to investigate the incidence, clinical course and short term outcomes of new-onset postoperative atrial fibrillation (POAF) following coronary artery bypass surgery (CABG). MATERIALS AND METHODS: A nation-wide study on 1622 patients who underwent CABG from 2006-2020 at Landspitali University Hospital. Clinical data were extracted from registries and 121 patients with pre-existing AF excluded, leaving 1501 patients for further analysis. Patient charts and postoperative ECGs were manually reviewed for determining details of POAF, which was defined as a postoperative episode of AF before discharge lasting at least 5 minutes. Patients with POAF (n=483) were compared to non-POAF patients (n=1018). RESULTS: Altogether 483 (32.2%) patients developed POAF; the annual incidence decreasing over time (tau= -0,45, p=0.023). Most patients were diagnosed on the second day postoperatively (43.5%) and over 90% were diagnosed within 4 days. The median number of POAF episodes was 3 (IQR: 1-5), the first episode lasting 1-6 hours in half of the cases and the total POAF-duration being 12 hours median (IQR: 5-30). Over 94% of cases converted to sinus rythm before discharge, with 25 (5.3%) patients being discharged in AF. Most patients were treated with beta-blockers (98.8%), amiodarone (95%) and 14.9% with electric cardioversion. POAF-patients were older, had higher EuroSCORE II and a longer hospital stay, however, they had similar rates of early postoperative stroke and 30 day mortality. CONCLUSION: The incidence of POAF remains high and was associated with prolonged hospital stay, but not significantly higher 30 day mortality or early postoperative stroke compared to patients in sinus rhythm. POAF-episodes were predominantly transient and almost 95% of patients were discharged in sinus rythm.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Incidência , Fatores de Risco , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , Progressão da DoençaRESUMO
INTRODUCTION: Perioperative myocardial infarction (PMI) after CABG can contribute to in-hospital morbidity and mortality, however, its clinical significance on long-term outcome, remains inadequately addressed. We studied both 30-day mortality and long-term effects of PMI in Icelandic CABG-patients. MATERIALS AND METHODS: A retrospective nationwide-study on 1446 consecutive CABG-patients operated at Landspitali in Iceland 2002-2018 without evidence of preoperative myocardial infarction. PMI was defined as a tenfold elevetion in serum-CK-MB associated with new ECG changes or diagnostic imaging consistent with ischemia. Patients with PMI were compared to a reference group with uni- and multivariate analyses. Long-term and MACCE-free survival were estimated with the Kaplan-Meier method and logistic regression used to determine factors associated with PMI. The mean follow-up time was 8.3 years. RESULTS: Out of 1446 patients 78 (5.4%) were diagnosed with PMI (range: 0-15.5%) with a significant annual decline in the incidence of PMI (12.7%, p<0.001). Over the same period preoperative aspirin use increased by 22.3% (p<0.018). PMI patients had a higher rate of short-term complications and a 11.5% 30-day mortality rate compared to 0.4% for non-PMI patients. PMI was found to be a predictor of 30-day mortality (OR 15.44, 95% CI: 6.89-34.67). PMI patients had worse 5-year MACCE-free survival (69.2% vs. 84.7, p=0,01), although overall survival was comparable between the groups. CONCLUSIONS: Although PMI after CABG is associated with significantly higher rates of short-term complications and 30-day mortality, long-term survival was similar to the reference group. Therefore, the mortality risk attributable to PMI appears to diminish after the immediate postoperative period.
Assuntos
Infarto do Miocárdio , Humanos , Incidência , Estudos Retrospectivos , Infarto do Miocárdio/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , AspirinaRESUMO
The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathological remodeling, resulting in heart failure. Few previous studies, however, have characterized the different chambers at a transcriptomic level. We, therefore, conducted whole tissue RNA sequencing and gene set enrichment analysis of biopsies collected from the four chambers of adult failing (n = 8) and nonfailing (n = 11) human hearts. Atria and ventricles demonstrated distinct transcriptional patterns. When compared with nonfailing ventricles, the transcriptional pattern of nonfailing atria was enriched for many gene sets associated with cardiogenesis, the immune system and bone morphogenetic protein (BMP), transforming growth factor-ß (TGF-ß), MAPK/JNK, and Wnt signaling. Differences between failing and nonfailing hearts were also determined. The transcriptional pattern of failing atria was distinct compared with that of nonfailing atria and enriched for gene sets associated with the innate and adaptive immune system, TGF-ß/SMAD signaling, and changes in endothelial, smooth muscle cell, and cardiomyocyte physiology. Failing ventricles were also enriched for gene sets associated with the immune system. Based on the transcriptomic patterns, upstream regulators associated with heart failure were identified. These included many immune response factors predicted to be similarly activated for all chambers of failing hearts. In summary, the heart chambers demonstrate distinct transcriptional patterns that differ between failing and nonfailing hearts. Immune system signaling may be a hallmark of all four heart chambers in failing hearts and could constitute a novel therapeutic target.NEW & NOTEWORTHY The transcriptomic patterns of the four heart chambers were characterized in failing and nonfailing human hearts. Both nonfailing atria had distinct transcriptomic patterns characterized by cardiogenesis, the immune system and BMP/TGF-ß, MAPK/JNK, and Wnt signaling. Failing atria and ventricles were enriched for gene sets associated with the innate and adaptive immune system. Key upstream regulators associated with heart failure were identified, including activated immune response elements, which may constitute novel therapeutic targets.
Assuntos
Insuficiência Cardíaca , Transcriptoma , Adulto , Humanos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Átrios do Coração/metabolismo , Perfilação da Expressão Gênica , Fator de Crescimento Transformador beta/metabolismo , Miocárdio/metabolismoRESUMO
AIMS: To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). METHODS AND RESULTS: From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. CONCLUSION: In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Fibrinolíticos , Fatores de Risco , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Sistema de RegistrosRESUMO
The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investigator-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Estudos Prospectivos , Aspirina/uso terapêutico , Ponte de Artéria Coronária , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Apêndice Atrial/cirurgia , Resultado do Tratamento , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: The initiating step in atherogenesis is the electrostatic binding of LDL (low-density lipoprotein) to proteoglycan glycosaminoglycans in the arterial intima. However, although proteoglycans are widespread throughout the intima of most coronary artery segments, LDL is not evenly distributed, indicating that LDL retention is not merely dependent on the presence of proteoglycans. We aim to identify factors that promote the interaction between LDL and the vessel wall of human coronary arteries. METHODS: We developed an ex vivo model to investigate binding of labeled human LDL to human coronary artery sections without the interference of cellular processes. RESULTS: By staining consecutive sections of human coronary arteries, we found strong staining of sulfated glycosaminoglycans throughout the arterial intima, whereas endogenous LDL deposits were focally distributed. Ex vivo binding of LDL was uniform at all intimal areas with sulfated glycosaminoglycans. However, lowering the pH from 7.4 to 6.5 triggered a 35-fold increase in LDL binding. The pH-dependent binding was abolished by pretreating LDL with diethyl-pyrocarbonate, which blocks the protonation of histidine residues, or cyclohexanedione, which inhibits the positive charge of site B on LDL. Thus, both histidine protonation and site B are required for strong electrostatic LDL binding to the intima. CONCLUSIONS: This study identifies histidine protonation as an important component for electrostatic LDL binding to human coronary arteries. Our findings show that the local pH will have a profound impact on LDL's affinity for sulfated glycosaminoglycans, which may influence the retention and accumulation pattern of LDL in the arterial vasculature.
Assuntos
Vasos Coronários , Lipoproteínas LDL , Vasos Coronários/metabolismo , Glicosaminoglicanos/metabolismo , Histidina , Humanos , Concentração de Íons de Hidrogênio , Lipoproteínas LDL/metabolismo , Proteoglicanas/metabolismo , Eletricidade EstáticaRESUMO
INTRODUCTION: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. METHODS: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016-2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. RESULTS: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16-1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09-1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26-6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03-7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution (n = 29, 78.4%), and/or extra heparin (n = 23, 62.2%), and/or epoprostenol (n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17-15.57), p = 0.011). CONCLUSIONS: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.
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Ponte Cardiopulmonar , Acidente Vascular Cerebral , Humanos , Ponte Cardiopulmonar/métodos , Epoprostenol , Oxigenadores , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were-0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.
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Ácido Araquidônico/efeitos adversos , Aspirina/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Aborto Habitual , Adulto , Estudos de Casos e Controles , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. METHODS: Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. RESULTS: The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 ± 6.3 vs. 2.5 ± 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p < .001) compared to the crystalloid group. The incidence of AKI was 18% in the colloid and 22% in the crystalloid group (p = .66). Postoperative serum creatinine did not differ between groups. CONCLUSIONS: In patients undergoing cardiac surgery with CPB, colloid-based priming solution (dextran 40) induced less renal tubular injury compared to a crystalloid-based priming solution. Whether a colloid-based priming solution will improve renal outcome in high-risk cardiac surgery, or not, needs to be evaluated in future studies on higher risk cardiac surgery patients.
Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Adulto , Ponte Cardiopulmonar , Dextranos , Humanos , Rim/fisiologiaRESUMO
BACKGROUND: Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery. METHODS: Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood-brain barrier injury marker ß-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients' age, operation time, and degree of hemolysis. RESULTS: No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145% (783%-2158%), GFAP +17% (-3%-43%), NSE +168% (106%-228%), while ß-trace protein was reduced (-11% (-17-3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis. CONCLUSION: Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood-brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.
Assuntos
Lesões Encefálicas , Procedimentos Cirúrgicos Cardíacos , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar , Hemólise , Humanos , Fosfopiruvato Hidratase , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
AIMS: To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease. METHODS AND RESULTS: We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41-0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17-1.38, Ptrend < 0.001). CONCLUSION: In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.
Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Idoso , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologia , Resultado do TratamentoRESUMO
AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to ß-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of ß1-adrenergic receptors. CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain ß-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
Assuntos
Glucosiltransferases , Miócitos Cardíacos , Animais , Cardiomegalia , Glucosiltransferases/genética , Camundongos , Receptores AdrenérgicosRESUMO
Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.
Assuntos
Apêndice Atrial/cirurgia , Bioprótese/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Fibrinogen concentrate is used clinically to improve hemostasis in bleeding patients. We investigated and compared the efficacy of three commercially available fibrinogen concentrates to improve clot strength in blood samples from cardiac surgery patients. OBJECTIVES: Postoperative blood samples were collected from 23 cardiac surgery patients. Samples were each divided into four vials, each supplemented with 1.125 mg of fibrinogen of one of three fibrinogen concentrates (RiaSTAP® , Fibryga® , FibCLOT® ), or placebo. The fibrinogen dose corresponded to 2.5 g per 70 kg of body weight. Clot strength after supplementation was assessed in duplicate with rotational thromboelastometry (ROTEM® ) using FIBTEM maximum clot firmness, EXTEM clot formation time, and maximum clot firmness assays. RESULTS: In vitro fibrinogen concentrate supplementation of the samples resulted in higher plasma fibrinogen concentrations and improved clot strength with all three concentrates. Supplementation with FibCLOT increased FIBTEM maximum clot firmness (+46% [25th-75th percentile 35-55] compared to placebo) significantly more than did supplementation with Fibryga (+26% [21-35]) and RiaSTAP (+29% [22-47], p < .001). FibCLOT supplementation also shortened EXTEM clot formation time and increased EXTEM maximum clot firmness to a greater extent than did the other concentrates (both p < .001). CONCLUSIONS: At the selected dose, FibCLOT was more effective than Fibryga and RiaSTAP in restoring clot strength in postoperative blood samples from cardiac surgery patients. These results may have implications for the choice of fibrinogen concentrate and dosing.