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1.
Tidsskr Nor Laegeforen ; 141(1)2021 Jan 12.
Artigo em No, Inglês | MEDLINE | ID: mdl-33433087

RESUMO

BACKGROUND: Patients with atrial fibrillation and atrial flutter scheduled to undergo open heart surgery can receive ablation treatment of arrhythmogenic foci during the same intervention. Sinus rhythm is restored in the majority in the short term, but the long-term results are more uncertain. This study, which is part of the international CURE-AF trial, evaluates results after Cox-Maze IV surgery for atrial fibrillation in Norway at six-year follow-up. MATERIAL AND METHOD: Nineteen patients were included in this prospective cohort study. Atrial fibrillation had persisted for 40 months in the group with long-standing persistent atrial fibrillation (n = 12) and 6 months in the group with persistent atrial fibrillation (n = 7). Surgery for atrial fibrillation was performed according to the Cox-Maze IV procedure in the CURE-AF protocol. Follow-up in the first 12 months was strictly according to the CURE-AF protocol, thereafter conducted by the primary health service. RESULTS: Sinus rhythm was restored in 11 patients at the time of discharge and in 14 patients six months postoperatively. After 5-6 years of follow-up, all patients with long-standing persistent atrial fibrillation had experienced recurrence. Two achieved sinus rhythm after electroconversion. Six of the seven in the group with persistent atrial fibrillation had sinus rhythm after 5-6 years. INTERPRETATION: The results were good initially, with restoration of sinus rhythm in more than two thirds of the patients after 6-9 months. Five years later, a high recurrence rate was found in patients with long-standing persistent atrial fibrillation. Several recurrences had not been detected by the public health service or treatment had not been attempted.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33346352

RESUMO

OBJECTIVES: The aim was to compare the relative effects of red blood cell (RBC) transfusion and preoperative anaemia on 5-year mortality following open-heart cardiac surgery using structural equation modelling. We hypothesized that patient risk factors associated with RBC transfusion are of larger importance than transfusion itself. METHODS: This prospective cohort study, part of the Cardiac Surgery Outcome Study at St. Olavs University Hospital, Trondheim, Norway, included open-heart on-pump cardiac surgery patients operated on from 2000 through 2017 (n = 9315). Structural equation modelling, which allows for intervariable correlations, was used to analyse pathway diagrams between known risk factors and observed mortality between 30 days and 5 years postoperatively. Observation times between 30 days and 1 year, and 1-5 years postoperatively were also compared with the main analysis. RESULTS: In a simplified model, preoperative anaemia had a larger effect on 5-year mortality than RBC transfusion (standardized coefficients: 0.17 vs 0.09). The complete model including multiple risk factors showed that patient risk factors such as age (0.15), anaemia (0.10), pulmonary disease (0.11) and higher creatinine level (0.12) had larger effects than transfusion (0.03). Results from several sensitivity analyses supported the main findings. The models showed good fit. CONCLUSIONS: Preoperative anaemia had a larger impact on 5-year mortality than RBC transfusion. Differences in 5-year mortality were mainly associated with patient risk factors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33179723

RESUMO

OBJECTIVES: Our goal was to study long-term observed and relative survival after first-time aortic valve replacement surgery with or without concomitant coronary artery bypass surgery with reference to valve morphology (i.e. bicuspid vs tricuspid). METHODS: Consecutive patients (n = 5086) from 3 Swedish hospitals, operated on between 1 January 2005 and 31 December 2016, were included. The 30-day mortality (n = 116, 2.3%) was excluded from the analysis of long-term observed and relative survival (n = 4970). Observed survival was analysed using Cox regression. Relative survival was calculated as the ratio between observed and expected survival based on data from the general Swedish population, matched for age, sex and calendar year. Risk factors for death were explored using multivariable analysis. RESULTS: During the follow-up (median 4.7 years) period, 1157 (23%) patients died. Observed survival excluding 30-day mortality was 96.6%, 82.7% and 57.6% after 1, 5 and 10 years. Compared with the general Swedish population, the relative 1-, 5- and 10-year survival rates were 99.0%, 97.5% and 89.0%. Bicuspid morphology was independently associated with higher observed and relative long-term survival. Renal dysfunction, diabetes, chronic obstructive pulmonary disease, heart failure, smoking and atrial fibrillation were associated with higher long-term mortality. Combined surgery was not associated with higher observed or relative mortality. CONCLUSIONS: Patients with a bicuspid morphology had better prognosis, matching that of the general population. With increased age, long-term relative survival compared favourably with survival in the general Swedish population. Adding coronary artery bypass surgery to an aortic valve replacement procedure did not affect long-term outcome.

4.
Interact Cardiovasc Thorac Surg ; 31(3): 375-382, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32725116

RESUMO

OBJECTIVES: Our goal was to investigate long-term mortality associated with red blood cell (RBC) transfusion among patients with anaemia undergoing cardiac surgery when adjusting for known risk factors. METHODS: Adults with preoperative anaemia as defined by World Health Organization criteria undergoing open-heart surgery from 2000 through 2017 were included. Cox regression was performed for long-term mortality (30 days-5 years), comparing patients who received ≥1 unit of RBC with those who did not. Unadjusted and multivariable analyses adjusted for risk factors were performed. RESULTS: The study included 1859 patients, 1525 (82%) of whom received RBC transfusion. A total of 370 (19.9%) deaths were registered between 30 days and 5 years; 88 patients (23.8%) died between 30 days and 1 year. The unadjusted hazard ratio (HR) associated with RBC transfusion was 2.09 (1.49-2.93, P < 0.001) from 30 days to 5 years postoperatively. The HR for RBC transfusion were 4.70 (1.72-12.81, P = 0.002) and 1.77 (1.23-2.55, P = 0.002) for 30 days-1 year and 1-5 years, respectively. Adjusting for perioperative risk factors, which included postoperative complications, the HR decreased to 1.16 (0.80-1.68, P = 0.43), 1.79 (0.63-5.12, P = 0.28) and 1.11 (0.75-1.65, P = 0.61) for observation time from 30 days to 5 years, 30 days to 1 year and 1 to 5 years, respectively. Results were similar when postoperative complications were excluded from the adjustment variables. CONCLUSIONS: No statistically significant association between RBC transfusion and long-term mortality was found when we adjusted for known risk factors. This study suggests that the observed difference in mortality in this patient group is largely due to patient-related risk factors.

6.
Perfusion ; 35(3): 236-245, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31446845

RESUMO

BACKGROUND: Patients with preoperative dual antiplatelet therapy prior to coronary artery bypass surgery are at risk of bleeding and blood component transfusion. We hypothesise that an optimised cardiopulmonary bypass strategy reduces postoperative blood loss and transfusions. METHODS: In total, 60 patients admitted for coronary artery bypass grafting with ticagrelor and aspirin medication withdrawn <96 hours before surgery were prospectively randomised into two equal sized groups. Cardiopulmonary bypass combined a closed Cortiva® heparin-coated circuit with low systemic heparinisation (activated clotting time < 250 seconds) and intraoperative cell salvage in the study group, whereas the control group used a Balance® coated open circuit, full systemic heparinisation (activated clotting time > 480 seconds) and conventional cardiotomy suction. This perfusion strategy was evaluated by the chest drain volume after 24 hours, perioperative haemoglobin and platelet loss accompanied by global coagulation assessments. RESULTS: Patients in the study group demonstrated significantly better outcomes signified by lower blood loss 554 ± 224 versus 1,100 ± 989 mL (p < 0.001), reduced packed red cell transfusion 7% versus 53% (p < 0.001), reduced haemoglobin -28 ± 15 versus -40 ± 14 g/L (p = 0.004) and platelet loss -35 ± 36 versus -82 ± 67 × 109/L (p = 0.001). Indices of rotational thromboelastometry indicated shorter clotting times within the internal and external pathways. Adenosine diphosphate activated platelet function was within normal range based on Multiplate® aggregometry, while ROTEM® platelet analyses indicated inhibited function both preoperatively and post-bypass. Platelet inhibition by aspirin was verified throughout the perioperative period. Platelet function showed no intergroup differences. CONCLUSION: A stringent perfusion strategy reduced blood loss and transfusions in dual antiplatelet therapy patients requiring urgent surgery.

7.
J Pain Symptom Manage ; 59(4): 818-828.e1, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31733353

RESUMO

CONTEXT: Lung cancer surgery is among the surgical procedures associated with the highest prevalence of pain, but prospective longitudinal studies after the pain trajectory are scarce. OBJECTIVES: We aimed to describe the pain trajectory in patients undergoing surgery for primary lung cancer and investigate whether distinct groups of patients could be identified based on different pain trajectories. METHODS: Patients (n = 264; 95% thoracotomies) provided data on the average and worst pain intensity, pain location, and comorbidities before, and at one month and five, nine, and 12 months after surgery. Pain profiles were analyzed by latent class mixed models. RESULTS: The occurrence of any pain increased from 40% before surgery to 69% after one month and decreased to 56%, 57%, and 55% at five, nine, and 12 months, respectively. Latent class mixed models identified two classes both for average and worst pain; one class started low with high ratings after one month, then returning to a level slightly higher than baseline. The other class started higher with similar scores through the trajectory. Patients reporting no pain (8%) were placed in a separate class. Higher comorbidity score, preoperative use of both pain and psychotropic medicine characterized the class with overall highest pain for average and/or worst pain. CONCLUSION: Pain was highly prevalent after surgery, and subgroups could be identified based on different pain trajectories. Patients reported both postoperative pain and pain from chronic conditions. Knowledge about vulnerable patients and risk factors for pain is important to tailor interventions and information about pain.

10.
Eur J Med Chem ; 185: 111783, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732257

RESUMO

Over the past decade, many drug discovery endeavors have been invested in targeting the serine proteases prolyl oligopeptidase (POP) for the treatment of Alzheimer's and Parkinson's disease and, more recently, epithelial cancers. Our research group has focused on the discovery of reversible covalent inhibitors, namely nitriles, to target the catalytic serine residue in this enzyme. While there have been many inhibitors discovered containing a nitrile to covalently bind to the catalytic serine, we have been investigating others, particularly boronic acids and boronic esters, the latter of which have been largely unexplored as covalent warheads. Herein we report a series of computationally-designed POP boronic ester pro-drug inhibitors exhibiting nanomolar-potencies in vitro as their active boronic acid species. These easily-accessible (1-2 step syntheses) compounds could facilitate future biochemical and biological studies of this enzyme's role in neurodegenerative diseases and cancer progression.


Assuntos
Ácidos Borônicos/farmacologia , Descoberta de Drogas , Ésteres/farmacologia , Pró-Fármacos/farmacologia , Serina Endopeptidases/metabolismo , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Relação Dose-Resposta a Droga , Ésteres/síntese química , Ésteres/química , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Relação Estrutura-Atividade
12.
J Med Chem ; 62(17): 7874-7884, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31393718

RESUMO

Over the past decade, there has been increasing interest in covalent inhibition as a drug design strategy. Our own interest in the development of prolyl oligopeptidase (POP) and fibroblast activation protein α (FAP) covalent inhibitors has led us to question whether these two serine proteases were equal in terms of their reactivity toward electrophilic warheads. To streamline such investigations, we exploited both computational and experimental methods to investigate the influence of different reactive groups on both potency and binding kinetics using both our own series of POP inhibitors and others' discovered hits. A direct correlation between inhibitor reactivity and residence time was demonstrated through quantum mechanics methods and further supported by experimental studies. This computational method was also successfully applied to FAP, as an overview of known FAP inhibitors confirmed our computational predictions that more reactive warheads (e.g., boronic acids) must be employed to inhibit FAP than for POP.

13.
J Cardiothorac Vasc Anesth ; 33(12): 3309-3319, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31350147

RESUMO

OBJECTIVE: Investigate important clinical and operative variables associated with increases in cardiac troponin T (cTnT) as indicators of myocardial injury after coronary artery bypass grafting (CABG). DESIGN: Prospective cohort study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 626 patients undergoing isolated CABG from April 2008 through April 2010 with a validation cohort (n = 686) from 2015-2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Perioperative variables were registered prospectively. The extent of diffuse coronary atherosclerosis and significant stenoses were assessed with preoperative coronary angiography. Mixed model analysis was used to construct a statistical model explaining the course of cTnT concentrations. The model was adjusted for preoperative and intraoperative/postoperative myocardial infarction (MI) for independent assessment of additional variables. Clinical factors associated with increased cTnT concentrations during and after CABG were longer duration of cardiopulmonary bypass (p < 0.001), higher preoperative creatinine (p < 0.001), New York Heart Association functional classification IV (p = 0.006), reduced LVEF (p = 0.034), higher preoperative C-reactive protein (p = 0.049), and intraoperative/postoperative MI (p < 0.001). Factors associated with decreasing cTnT concentrations during CABG were higher BSA (p < 0.001) and a recent preoperative MI (p < 0.001). The extent of diffuse coronary atherosclerosis and significant stenoses were not associated with changes in cTnT (p = 0.35). Results were similar in the validation cohort. CONCLUSIONS: Left ventricular ejection fraction, New York Heart Association classification, kidney function, inflammation status, duration of cardiopulmonary bypass, body surface area, and preoperative MI were associated with the cTnT rise-and-fall pattern related to myocardial injury after CABG. Information regarding these variables may be valuable when using cTnT in the diagnostic workup of postoperative MI.

14.
Scand Cardiovasc J ; 53(4): 220-224, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169422

RESUMO

Objectives. Two tools to categorize and present quality data, phase of care mortality analysis (POCMA) and failure to rescue (FTR) have been introduced in the cardiothoracic surgical environment, but not tested in Scandinavia. We aimed to investigate whether these tools could be used in a Norwegian patient population and to increase the understanding of why patients die after cardiac surgery. Design. A group of four, including one senior cardiothoracic surgeon and one senior anesthesiologist, scrutinized deaths within 30 days after cardiac surgery at the Clinic of Cardiothoracic Surgery, St. Olav's University Hospital, Norway between February 2012-October 2015 in line with the POCMA-methodology. We used the clinic's internal register to identify patients and utilized all available written information from each patient course. We decided whether each death was surgeon dependent, FTR or a result of a multifactorial etiology, and evaluated the strength of our decisions. Results. We identified 51 deaths out of 1983 operations in our study period, giving unadjusted mortality of 2.6%. Nine deaths were classified as surgeon dependent, 3 FTR and 39 multifactorial. Conclusions. POCMA- and FTR-analyses can be carried out in clinical data which is well documented. The operating surgeon is in many cases not responsible for operative mortality, very few die due to FTR, but most patients die due to a multifactorial etiology.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Serviço Hospitalar de Cardiologia , Unidades de Cuidados Coronarianos , Falha da Terapia de Resgate , Mortalidade Hospitalar , Indicadores de Qualidade em Assistência à Saúde , Procedimentos Cirúrgicos Vasculares/mortalidade , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Causas de Morte , Competência Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
16.
J Thorac Cardiovasc Surg ; 156(6): 2183-2190.e2, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30319093

RESUMO

OBJECTIVES: Health-related quality of life (HRQOL) is an important end point after cardiac surgery, particularly in patients of older age. However, prospective long-term studies describing the trajectory of HRQOL after cardiac surgery are still scarce. Therefore, the aim was to assess survival, functional status, and trajectory of HRQOL 10 years after cardiac surgery. METHODS: In a prospective population-based study, 534 patients (23% aged 75 years or older, 67% male) were consecutively included before surgery. Functional status was measured according to self-assigned New York Heart Association (NYHA) classification. HRQOL was measured using the Short-Form Health Survey (SF-36). Questionnaires were given to the patients at baseline and sent by post at 6 and 12 months, and 5 and 10 years after surgery. RESULTS: Three hundred fifty-two patients were eligible after 10 years, 274 responded (77.8%). Total survival at 10 years was 67.8%. Patients aged 75 years or older at surgery had lower survival rates than younger patients (44.6% vs 74.6%, P < .001). Seven of 8 SF-36 subscales were improved at 10 years compared with baseline. Older patients improved less than younger patients and linear mixed models showed that older patients had significantly worse trajectories on 3 of 8 SF-36 subscales. NYHA classification improved from baseline to 10 years also among older patients, with 59% in NYHA class III/IV at baseline compared with 30.3% after 10 years (P < .013). CONCLUSIONS: HRQOL and function improved from before to 10 years after cardiac surgery, also for older patients. These long-term results are of major importance when discussing the use of health care resources and patient-centered clinical decision-making.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Qualidade de Vida , Sobreviventes , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Saúde Mental , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sobreviventes/psicologia , Fatores de Tempo , Resultado do Tratamento
17.
ESC Heart Fail ; 5(3): 332-342, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29431258

RESUMO

AIMS: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. METHODS AND RESULTS: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+ , lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (-35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (-26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. CONCLUSIONS: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF.


Assuntos
Cálcio/metabolismo , Insuficiência Cardíaca/etiologia , Contração Miocárdica/fisiologia , Infarto do Miocárdio/complicações , Miócitos Cardíacos/metabolismo , Biópsia , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Volume Sistólico/fisiologia
18.
Interact Cardiovasc Thorac Surg ; 27(1): 95-101, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29447379

RESUMO

OBJECTIVES: During open-heart surgery, the myocardium experiences ischaemia-reperfusion injury. A single bout of moderate, 30-min exercise induces preconditioning and protects the heart from ischaemia-reperfusion injury in rats, but this has never been investigated in humans. We aimed to investigate whether 1 bout of moderate exercise 24 h prior to surgery protects against mitochondrial and cardiac damage. METHODS: Patients scheduled for elective coronary artery bypass were eligible for this pilot study. Twenty were included and randomized to the treadmill exercise group (the EX group, n = 10) 24 h preoperatively or to standard presurgical procedures (control n = 10). Right atrial (RA) and left ventricular (LV) biopsies were collected immediately before and as long as possible after aortic cross-clamping to assess the primary outcome of mitochondrial respiration by respirometry, in addition to reactive oxygen species production by fluorometry and apoptotic transcripts. Cardiac troponin T and creatine kinase myocardial brain were measured in plasma at arrival, before surgery and 6 and 24 h postoperatively. RESULTS: Mitochondrial respiration was lower in the EX group after surgery in the LV (Complex I -22%, P < 0.05 and maximal -23%, P < 0.05) and the right atrium (Complex I -25%, P < 0.05). Transcript level of the apoptosis-related marker caspase 3 was increased 1.5-fold in the LV prior to surgery in the EX group when compared with the control group, P < 0.05. Cardiac troponin T was 45% higher in the EX group than in the control group 6 h postoperatively (P = 0.03), although not significant when corrected for aortic cross-clamping time. CONCLUSIONS: Results indicate that exercise did not precondition the heart against surgery-related damage. Exercise may render the myocardium and mitochondria more vulnerable to perioperative damage. Clinical trials registration number: NCT00218985 (https://clinicaltrials.gov/ct2/show/NCT00218985).


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Exercício Físico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Idoso , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Creatina Quinase Forma MB/sangue , Procedimentos Cirúrgicos Eletivos , Feminino , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Miocárdio/patologia , Projetos Piloto , Troponina T/sangue
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