| 1. |
- Chemtob, Raphaelle A, et al.
(författare)
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Stroke in acute type A aortic dissection: the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD).
- 2020
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - 1873-734X. ; 58:5, s. 1027-1034
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Tidskriftsartikel (refereegranskat)abstract
- Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients.The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014.Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P<0.001), syncope (30.6% vs 17.6%, P<0.001), cardiogenic shock (33.1% vs 20.7%, P<0.001) and pericardial tamponade (25.9% vs 14.7%, P<0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P=0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P<0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P<0.001).Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
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| 2. |
- Barbu, Mikael, et al.
(författare)
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Dextran- versus crystalloid-based prime in cardiac surgery: A prospective randomized pilot study.
- 2020
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Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 110:5, s. 1541-7
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Tidskriftsartikel (refereegranskat)abstract
- The optimum priming fluid for the cardiopulmonary bypass (CPB) circuit is still debated. We compared a new hyperoncotic priming solution containing dextran 40, which has an electrolyte composition that mimics extracellular fluid, with a standard crystalloid-based prime.Eighty cardiac surgery patients were included in this double-blind randomized single-centre study. The patients were randomized to either a dextran-based prime or a crystalloid prime containing Ringer acetate and mannitol. The primary endpoint was colloid oncotic pressure (COP) in serum during CPB. Secondary endpoints included fluid balance, bleeding and transfusion requirements, pulmonary function, hemolysis, systemic inflammation, and markers of renal, hepatic, myocardial, and brain injury. Blood samples were collected before, during, and after CPB.COP was higher in the dextran group than in the crystalloid prime group on CPB (18.8±2.9 vs. 16.4±2.9 mmHg, p<0.001) and 10 min after CPB (19.2±2.7 vs. 16.8±2.9 mmHg, p<0.001). Patients in the dextran group required less intravenous fluid during CPB (1090±499 vs. 1437±543 ml; p=0.003) and net fluid balance was less positive 12h after surgery (+1,431±741 vs. +1,901±922 ml; p=0.014). Plasma free hemoglobin was significantly lower in the dextran group 2h after CPB (0.18±0.11 vs 0.41±0.33, p=0.001). There were no significant differences in bleeding, transfusion requirements, organ function, systemic inflammation, or brain and myocardial injury markers between the groups at any time point.Our results suggest that a hyperoncotic dextran-based priming solution preserves intraoperative COP compared to crystalloid prime. Larger studies with clinically valid endpoints are necessary to evaluate hyperoncotic prime solutions further.
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| 3. |
- Christersson, Christina, et al.
(författare)
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Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
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| 4. |
- Helgason, Dadi, et al.
(författare)
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Acute Kidney Injury Following Acute Repair of Type A Aortic Dissection.
- 2021
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Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 111:4, s. 1292-1298
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the incidence, risk factors and outcomes of patients with acute kidney injury (AKI) following surgery for acute type A aortic dissection (ATAAD) using the NORCAAD registry.Patients that underwent ATAAD surgery at eight Nordic centers from 2005-2014 were analyzed for AKI according to the RIFLE-criteria. Patients who died intraoperatively, those who had missing baseline or postoperative serum creatinine (SCr), and patients on preoperative RRT, were excluded.AKI occurred in 382/941 (40.6%) patients and postoperative dialysis was required for 105 (11.0%) patients. Renal malperfusion was present preoperatively in 42 (5.1%) patients, of whom 69.0% developed postoperative AKI.In multivariable analysis, patient-related predictors of AKI included age (per 10 years, OR=1.30, 95% CI:1.15-1.48), body mass index>30 kg/m2 (OR=2.16, 95% CI:1.51-3.09), renal malperfusion (OR=4.39, 95% CI:2.23-9.07) and other malperfusion (OR:2.10, 95% CI:1.55-2.86). Perioperative predictors were cardiopulmonary bypass time (per 10 minutes, OR=1.04, 95% CI:1.02-1.07) and red blood cell transfusion (OR=1.08, 95% CI:1.06-1.10). Rates of 30-day mortality were 17.0% in the AKI group compared with 6.6% in the non-AKI group (p<0.001). In 30-day survivors, AKI was an independent predictor of long-term mortality (HR=1.86, 95% CI:1.24-2.79).AKI is a common complication following surgery for ATAAD and independently predicts adverse long-term outcome. Of note, one-third of patients presenting with renal malperfusion did not develop postoperative AKI, possibly due to restoration of renal blood flow with surgical repair. Mortality risk persists beyond the perioperative period, indicating that close clinical follow-up of these patients is required.
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| 5. |
- Nozohoor, Shahab, et al.
(författare)
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ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection
- 2020
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Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:2, s. 124-129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD).Design: A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality.Results: There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups.Conclusions: In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.
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| 6. |
- Synnergren, Jane, et al.
(författare)
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Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo
- 2020
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 52:2, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional studies of the human heart provide insight into physiological and pathophysiological mechanisms, essential for understanding the fundamental mechanisms of normal cardiac function and how they are altered by disease. To improve the understanding of why men and women may respond differently to the same therapeutic treatment it is crucial to learn more about sex-specific transcriptional differences. In this study the transcriptome of right atrium and left ventricle was compared across sex and regional location. Paired biopsies from five male and five female patients undergoing aortic valve replacement or coronary artery bypass grafting were included. Gene expression analysis identified 620 differentially expressed transcripts in atrial and ventricular tissue in men and 471 differentially expressed transcripts in women. In total 339 of these transcripts overlapped across sex but notably, 281 were unique in the male tissue and 162 in the female tissue, displaying marked sex differences in the transcriptional machinery. The transcriptional activity was significantly higher in atrias than in ventricles as 70% of the differentially expressed genes were upregulated in the atrial tissue. Furthermore, pathway- and functional annotation analyses performed on the differentially expressed genes showed enrichment for a more heterogeneous composition of biological processes in atrial compared with the ventricular tissue, and a dominance of differentially expressed genes associated with infection disease was observed. The results reported here provide increased insights about transcriptional differences between the cardiac atrium and ventricle but also reveal transcriptional differences in the human heart that can be attributed to sex.
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| 7. |
- Taha, Amar, 1978, et al.
(författare)
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New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.
- 2021
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30days after surgery. During follow-up (median 4.5years, range 0‒9years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.
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| 8. |
- Völz, Sebastian, 1980, et al.
(författare)
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Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention : insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:27, s. 2657-2664
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- 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 β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 10. |
- Anttila, V., et al.
(författare)
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Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
- 2020
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Ingår i: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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