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Sökning: WFRF:(Jeppsson Anders 1960)

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1.
  • Ahlsson, Anders, et al. (författare)
  • Is There a Weekend Effect in Surgery for Type A Dissection? : Results From the Nordic Consortium for Acute Type A Aortic Dissection Database
  • 2019
  • Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 108:3, s. 770-776
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Aortic dissection type A requires immediate surgery. In general surgery populations, patients operated on during weekends have higher mortality rates compared with patients whose operations occur on weekdays. The weekend effect in aortic dissection type A has not been studied in detail.Methods: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) registry includes data for 1,159 patients who underwent type A dissection surgery at 8 Nordic centers during 2005 to 2014. This study is based on data relating to surgery conducted during weekdays versus weekends and starting between 8:00 AM and 8:00 Pm ("daytime") versus from 8:00 Pm to 8:00 AM ("nighttime"), as well as time from symptoms, admittance, and diagnosis to surgery. The influence of timing of surgery on the 30-day mortality rate was assessed using logistic regression analysis.Results: The 30-day mortality was 18% (204 of 1,159), with no difference in mortality between surgery performed on weekdays (17% [150 of 889]) and on weekends (20% [54 of 270], p = 0.45), or during nighttime (19% [87 of 467]) versus daytime (17% [117 of 680], p = 0.54). Time from symptoms to surgery (median 7.0 hours vs 6.5 hours, p = 0.31) did not differ between patients who survived and those who died at 30 days. Multivariable regression analysis of risk factors for 30-day mortality showed no weekend effect (odds ratio, 1.04; 95% confidence interval, 60.67 to 1.60; p = 0.875), but nighttime surgery was a risk factor (odds ratio, 2.43; 95% confidence interval, 1.29 to 4.56; p = 0.006).Conclusions: The 30-day mortality in surgical repair of aortic dissection type A was not significantly affected by timing of surgery during weekends versus weekdays. Nighttime surgery seems to predict increased 30-day mortality, after correction for other risk factors.
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2.
  • Geirsson, Arnar, et al. (författare)
  • Hospital volumes and later year of operation correlates with better outcomes in acute Type A aortic dissection
  • 2018
  • Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press. - 1010-7940 .- 1873-734X. ; 53:1, s. 276-281
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Acute Type A aortic dissection remains a life-threatening disease, but there are indications that its surgical mortality is decreasing. The aim of this report was to study how surgical mortality has changed and what influences those changes.METHODS: Nordic Consortium for Acute Type A Aortic Dissection is a retrospective database comprising 1159 patients (mean age 61.6 ± 12.2 years, 68% male) treated for acute Type A aortic dissection at 8 centres in Denmark, Finland, Iceland and Sweden from 2005 to 2014. Data gathered included demographics, symptoms, type of procedure, complications and 30-day mortality.RESULTS: The annual number of operations increased significantly from 85 in 2005 to 150 in 2014 (P < 0.001). Chest pain was present in 85% of patients, 24% were hypotensive on presentation and 28% had malperfusion syndrome. Open distal anastomosis technique under hypothermic circulatory arrest was used in 85% of cases and its use increased significantly throughout the study. The 30-day mortality decreased from 24% in 2005 to 13% in 2014 (P = 0.003). Independent predictors for 30-day mortality were preoperative cardiac arrest, malperfusion syndrome, Penn Class C, Penn Class B and C and cardiopulmonary bypass time, whereas later calendar year and higher hospital operative volumes predicted improved survival.CONCLUSIONS: Surgical mortality for acute Type A aortic dissection remains high but has decreased significantly over the last decade. This correlated with later year of operation and increased the number of operations performed per year, indicating that cumulative surgical experience contributes significantly to improved surgical outcomes.
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3.
  • Bjurbom, Markus, et al. (författare)
  • Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery
  • 2023
  • Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 115:3, s. 591-598
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. Methods: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). Results: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). Conclusions: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.
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4.
  • Bjursten, Henrik, et al. (författare)
  • Once after a full moon : acute type A aortic dissection and lunar phases
  • 2022
  • Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press. - 1569-9293 .- 1569-9285. ; 34:1, s. 105-110
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD.METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period).RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated.CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
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5.
  • Chemtob, Raphaelle A, et al. (författare)
  • Stroke in acute type A aortic dissection: the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD).
  • 2020
  • 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
  • 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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6.
  • Geirsson, Arnar, et al. (författare)
  • Differential outcomes of open and clamp-on distal anastomosis techniques in acute type A aortic dissection
  • 2019
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:5, s. 1750-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique.Methods: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014.Results: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% +/- 4.4%) compared with the open-distal group (73.0% +/- 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival.Conclusions: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short-and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases.
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7.
  • Olsson, Christian, et al. (författare)
  • Medium-term survival after surgery for acute Type A aortic dissection is improving
  • 2017
  • Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press. - 1010-7940 .- 1873-734X. ; 52:5, s. 852-857
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To report long-term survival and predictors of mortality in patients included in a large, contemporary, multicentre, multinational database: Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD), which consists of 8 centres in 4 Nordic countries.METHODS: Currently, NORCAAD includes 1159 patients operated between 2005 and 2014. In 30-day survivors (n = 955, 82%), the Kaplan-Meier and Cox proportional hazard methods were used to analyse medium-term (up to 8 years) survival and relative survival versus a matched normal population. Pre- and intraoperative predictors were expressed as hazard ratio (HR) with 95% confidence interval (95% CI).RESULTS: Cumulative follow-up was 3514 patient-years with a median of 3.2 years (range 0-10.2 years). Survival was 95% (95% CI 93-96) at 1 year, 86% (95% CI 83-88) at 5 years and 76% (95% CI 72-81) at 8 years. Relative survival versus a matched normal population was 95% (95% CI 94-97) at 1 year, 90% (95% CI 87-93) at 5 years and 85% (95% CI 80-90) at 8 years. In multivariable analysis, increased age (HR 1.05 per year, 95% CI 1.04-1.07), previous abdominal or thoracic aortic repair (HR 3.2, 95% CI 1.6-6.4) and chronic renal disease (HR 2.7, 95% CI 1.2-6.2) were associated with increased medium-term mortality. Open distal anastomosis (HR 0.55, 95% CI 0.35-0.87) and operation in the 2010-2014 period (HR 0.90, 95% CI 0.83-0.97) were associated with decreased medium-term mortality.CONCLUSIONS: Medium-term survival after acute Type A aortic dissection in the NORCAAD registry is satisfactory, close to a matched normal population and improved in the later part of the study period. The use of open distal anastomosis was associated with decreased medium-term mortality.
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8.
  • Oudin, Anna, et al. (författare)
  • Impact of national holidays and weekends on incidence of acute type A aortic dissection repair
  • 2022
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.
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9.
  • Pan, Emily, et al. (författare)
  • Outcome after type A aortic dissection repair in patients with preoperative cardiac arrest
  • 2019
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 144, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM OF THE STUDY: Patients presenting with acute type A aortic dissection (ATAAD) and cardiac arrest before surgery are considered to have very poor prognosis, but limited data is available. We used a large database to evaluate the outcome of ATAAD patients with a cardiac arrest before surgery.METHODS: We evaluated 1154 surgically treated ATAAD patients from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database between 2005 and 2014. Patients with (n = 44, 3.8%) and without preoperative cardiac arrest were compared and variables univariably associated with mortality in the cardiac arrest group were identified. Median follow-up time was 2.7 years (interquartile range 0.5-5.5).RESULTS: Thirty-day mortality in the arrest and non-arrest group was 43.2% and 16.6%, respectively (odds ratio [OR] 3.83, CI 2.06-7.09; P < 0.001). In the nine patients with ongoing cardiopulmonary resuscitation when cardiopulmonary bypass was initiated, five died intraoperatively and one died after 65 days. In patients surviving the operation, stroke was significantly more common in the arrest group (48.4% vs 18.2%; OR 4.21, CI 2.05-8.67; P < 0.001). In total, 50.0% (22/44) of the arrest patients survived to the end of follow-up. Non-survivors in the arrest group more often had DeBakey type I dissection, cardiac tamponade, cardiac malperfusion and higher preoperative serum lactate (all P < 0.05).CONCLUSIONS: Early mortality and complications after ATAAD surgery in patients with a preoperative cardiac arrest are high, but mid-term outcome after surviving the initial period is acceptable. Preoperative cardiac arrest should not be considered an absolute contraindication for a surgical ATAAD repair.
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10.
  • Uimonen, Mikko, et al. (författare)
  • Outcome After Surgery for Acute Type A Aortic Dissection With or Without Primary Tear Resection
  • 2022
  • Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 114:2, s. 492-501
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The outcome in patients after surgery for acute type A aortic dissection without replacement of the part of the aorta containing the primary tear is undefined.METHODS: Data of 1122 patients who underwent surgery for acute type A aortic dissection in 8 Nordic centers from January 2005 to December 2014 were retrospectively analyzed. The patients with primary tear location unfound, un-known, not confirmed, or not recorded (n = 243, 21.7%) were excluded from the analysis. The patients were divided into 2 groups according to whether the aortic reconstruction encompassed the portion of the primary tear (tear resected [TR] group, n = 730) or not (tear not resected [TNR] group, n = 149). The restricted mean survival time ratios adjusted for patient characteristics and surgical details between the groups were calculated for all-cause mortality and aortic reoperation-free survival. The median follow-up time was 2.57 (interquartile range, 0.53-5.30) years.RESULTS: For the majority of the patients in the TR group, the primary tear was located in the ascending aorta (83.6%). The reconstruction encompassed both the aortic root and the aortic arch in 7.4% in the TR group as compared with 0.7% in the TNR patients (P < .001). There were no significant differences in all-cause mortality (adjusted restricted mean survival time ratio, 1.01; 95% confidence interval, 0.92-1.12; P = .799) or reoperation-free survival (adjusted restricted mean survival time ratio, 0.98; 95% confidence interval, 0.95-1.02; P = .436) between the TR and TNR groups.CONCLUSIONS: Primary tear resection alone does not determine the midterm outcome after surgery for acute type A aortic dissection. (Ann Thorac Surg 2022;114:492-501) (c) 2022 by The Society of Thoracic Surgeons.
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11.
  • Vukusic, Kristina, 1979, et al. (författare)
  • The Atrioventricular Junction: A Potential Niche Region for Progenitor Cells in the Adult Human Heart
  • 2019
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 28:16, s. 1078-1088
  • Tidskriftsartikel (refereegranskat)abstract
    • A stem cell niche is a microenvironment where stem cells reside in a quiescent state, until activated. In a previous rat model, we combined 5-bromo-2-deoxy-uridine labeling with activation of endogenous stem cells by physical exercise and revealed a distinct region, in the atrioventricular junction (AVj), with features of a stem cell niche. In this study, we aim to investigate whether a similar niche exists in the human heart. Paired biopsies from AVj and left ventricle (LV) were collected both from explanted hearts of organ donors, not used for transplantation (N = 7) and from severely failing hearts from patients undergoing heart transplantation (N = 7). Using antibodies, we investigated the expression of stem cell, hypoxia, proliferation and migration biomarkers. In the collagen-dense region of the AVj in donor hearts, progenitor markers, MDR1, SSEA4, ISL1, WT1, and hypoxia marker, HIF1-alpha, were clearly detected. The expression gradually decreased with distance from the valve. At the myocardium border in the AVj costaining of the proliferation marker Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin-T (cTnT) indicated proliferation of small cardiomyocytes. In the same site we also detected ISL1(+)/WT1(+)/cTnT cells. In addition, heterogeneity in cardiomyocyte sizes was noted. Altogether, these findings indicate different developmental stages of cardiomyocytes below the region dense in stem cell marker expression. In patients suffering from heart failure the AVj region showed signs of impairment generally displaying much weaker or no expression of progenitor markers. We describe an anatomic structure in the human hearts, with features of a progenitor niche that coincided with the same region previously identified in rats with densely packed cells expressing progenitor and hypoxia markers. The data provided in this study indicate that the adult heart contains progenitor cells and that AVj might be a specific niche region from which the progenitors migrate at the time of regeneration.
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12.
  • Zindovic, Igor, et al. (författare)
  • Malperfusion in acute type A aortic dissection : An update from the Nordic Consortium for Acute Type A Aortic Dissection
  • 2019
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:4, s. 1324-1333
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the effect of preoperative malperfusion on 30-day and late mortality and postoperative complications using data from the Nordic Consortium for Acute Type A Aortic Dissection (ATAAD) registry.Methods: We studied 1159 patients who underwent ATAAD surgery between January 2005 and December 2014 at 8 Nordic centers. Multivariable logistic and Cox regression analyses were performed to identify independent predictors of 30-day and late mortality.Results: Preoperative malperfusion was identified in 381 of 1159 patients (33%) who underwent ATAAD surgery. Thirty-day mortality was 28.9% in patients with preoperative malperfusion and 12.1% in those without. Independent predictors of 30-day mortality included any malperfusion (odds ratio, 2.76; 95% confidence interval [CI], 1.94-3.93), cardiac malperfusion (odds ratio, 2.37; 95% CI, 1.34-4.17), renal malperfusion (odds ratio, 2.38; 95% CI, 1.23-4.61) and peripheral malperfusion (odds ratio, 1.95; 95% CI, 1.26-3.01). Any malperfusion (hazard ratio, 1.72; 95% CI, 1.21-2.43), cardiac malperfusion (hazard ratio, 1.89; 95% CI, 1.24-2.87) and gastrointestinal malperfusion (hazard ratio, 2.25; 95% CI, 1.18-4.26) were predictors of late mortality. Malperfusion was associated with significantly poorer survival at 1, 3, and 5 years (95.0% +/-0.9% vs 88.7% +/-1.9%, 90.1% +/-1.3% vs 84.0% +/-2.4%, and 85.4% +/-1.7% vs 80.8% +/-2.7%; log rank P = .009).Conclusions: Malperfusion has a significant influence on early and late outcomes in ATAAD surgery. Management of preoperative malperfusion remains a major challenge in reducing mortality associated with surgical treatment of ATAAD.
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13.
  • Andersson, Henrik, et al. (författare)
  • Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
  • 2010
  • Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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14.
  • Asp, Julia, 1973, et al. (författare)
  • Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.
  • 2010
  • Ingår i: Journal of molecular cell biology. - : Oxford University Press (OUP). - 1759-4685 .- 1674-2788. ; 2:5, s. 276-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.
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15.
  • Barbu, Mikael, et al. (författare)
  • Cardiopulmonary bypass management and acute kidney injury in cardiac surgery patients.
  • 2024
  • Ingår i: Acta anaesthesiologica Scandinavica. - 1399-6576. ; 68:3, s. 328-336
  • Tidskriftsartikel (refereegranskat)abstract
    • 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).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 20s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics.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>90mL/min/m2 , and preoperative hemoglobin concentration below or above the normal sex-specific range.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.
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16.
  • Barbu, Mikael, et al. (författare)
  • Dextran- versus crystalloid-based prime in cardiac surgery: A prospective randomized pilot study.
  • 2020
  • Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 110:5, s. 1541-7
  • 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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17.
  • Chemtob, Raphaelle A., et al. (författare)
  • Effects of Sex on Early Outcome following Repair of Acute Type A Aortic Dissection : Results from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD)
  • 2019
  • Ingår i: AORTA. - : Georg Thieme Verlag KG. - 2325-4637. ; 7:1, s. 7-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Female sex is known to have increased perioperative mortality in cardiac surgery. Studies reporting effects of sex on outcome following surgical repair for acute Type A aortic dissection (ATAAD) have been limited by small cohorts of heterogeneous patient populations and have shown diverging results. This study aimed to compare perioperative characteristics, operative management, and postoperative outcome between sexes in a large and well-defined cohort of patients operated for ATAAD. Methods The Nordic Consortium for Acute Type A Aortic Dissection study included patients with surgical repair of ATAAD at eight Nordic centers between January 2005 and December 2014. Independent predictors of 30-day mortality were identified using multivariable logistic regression. Results Females represented 373 (32%) out of 1,154 patients and were significantly older (65 ± 11 vs. 60 ± 12 years, p < 0.001), had lower body mass index (25.8 ± 5.4 vs. 27.2 ± 4.3 kg/m 2, p < 0.001), and had more often a history of hypertension (59% vs. 48%, p = 0.001) and chronic obstructive pulmonary disease (8% vs. 4%, p = 0.033) compared with males. More females presented with DeBakey class II as compared with males with dissection of the ascending aorta alone (33.4% vs. 23.1%, p = 0.003). Hypothermic cardiac arrest time (28 ± 16 vs. 31 ± 19 minutes, p = 0.026) and operation time (345 ± 133 vs. 374 ± 135 minutes, p < 0.001) were shorter among females. There was no difference between the sexes in unadjusted intraoperative death (9.1% vs. 6.7%, p = 0.17) or 30-day mortality (17.7% vs. 17.4%, p = 0.99). In a multivariable analysis including perioperative factors influencing mortality, no difference was found between females and males in 30-day mortality (odds ratio: 0.92, 95% confidence interval: 0.62-1.38, p = 0.69). Conclusions This study found no association between sex and early mortality following surgery for ATAAD, despite females being older and having more comorbidities, yet also presenting with a less widespread dissection than males.
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18.
  • Christersson, Christina, et al. (författare)
  • Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
  • 2020
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
  • 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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19.
  • Grzymala-Lubanski, Bartosz, et al. (författare)
  • Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis.
  • 2017
  • Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 103:3
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the impact of time in therapeutic range (TTR) and international normalised ratio (INR) variability on the risk of thromboembolic events, major bleeding complications and death after mechanical heart valve (MHV) implantation. Additionally, the importance of different target INR levels was elucidated.
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20.
  • Gäbel, Jakob, 1971, et al. (författare)
  • Cell salvage of cardiotomy suction blood improves the balance between pro- and anti-inflammatory cytokines after cardiac surgery.
  • 2013
  • Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 44:3, s. 506-11
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The inflammatory response after cardiac surgery is characterized by a profound release of pro- and anti-inflammatory cytokines. Recent data suggest that the balance between pro- and anti-inflammatory cytokines is of greater importance than the absolute levels. Retransfusion of unwashed cardiotomy suction blood contributes to the inflammatory response, but the balance between pro- and anti-inflammatory cytokines in cardiotomy suction blood and whether cell salvage before retransfusion influences the systemic balance have not been investigated previously. METHODS: Twenty-five coronary artery bypass grafting patients were randomized to either cell salvage of cardiotomy suction blood or no cell salvage before retransfusion. Plasma levels of three anti-inflammatory cytokines [interleukin (IL)-1 receptor antagonist, IL-4 and IL-10] and two proinflammatory cytokines (tumour necrosis factor-alpha and IL-6), and the IL-6-to-IL-10 ratio was measured in cardiotomy suction blood before and after cell salvage, and in the systemic circulation before, during and after surgery. RESULTS: Plasma levels of all cytokines except IL-4 and IL-10 were significantly higher in cardiotomy suction blood than in the systemic circulation. The IL-6-to-IL-10 ratio was 6-fold higher in cardiotomy suction blood than in the systemic circulation [median 10.2 (range 1.1-75) vs 1.7 (0.2-24), P < 0.001]. Cell salvage reduced plasma levels of cytokines in cardiotomy suction blood and improved the systemic IL-6-to-IL-10 ratio 24 h after surgery [median 5.2 (3.6-17) vs 12.4 (4.9-31)] compared with no cell salvage (P = 0.032). CONCLUSIONS: The balance of pro- and anti-inflammatory cytokines in cardiotomy suction blood is unfavourable. Cell salvage reduces the absolute levels of both pro- and anti-inflammatory cytokines in cardiotomy suction blood and improves the balance in the systemic circulation after surgery.
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21.
  • Hansson, Emma C., 1985, et al. (författare)
  • Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel : a nationwide study
  • 2016
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:2, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS:Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients.METHODS AND RESULTS:All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012-13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72-120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53-1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72-120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04-2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56-0.92), P = 0.012].CONCLUSION:The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.
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22.
  • Hansson, Emma C., 1985, et al. (författare)
  • Preoperative dual antiplatelet therapy increases bleeding and transfusions but not mortality in acute aortic dissection type A repair.
  • 2019
  • Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X .- 1010-7940. ; 56:1, s. 182-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute aortic dissection type A is a life-threatening condition, warranting immediate surgery. Presentation with sudden chest pain confers a risk of misdiagnosis as acute coronary syndrome resulting in subsequent potent antiplatelet treatment. We investigated the impact of dual antiplatelet therapy (DAPT) on bleeding and mortality using the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database.The NORCAAD database is a retrospective multicentre database where 119 of 1141 patients (10.4%) had DAPT with ASA+clopidogrel (n=108) or ASA+ticagrelor (n=11) before surgery. The incidence of major bleeding and 30-day mortality was compared between DAPT and non-DAPT patients with logistic regression models before and after propensity score matching.Before matching, 51.3% of DAPT patients had major bleeding when compared to 37.7% of non-DAPT patients (P=0.0049). DAPT patients received more transfusions of red blood cells [median 8U (Q1-Q3 4-15) vs 5.5U (2-11), P<0.0001] and platelets [4U (2-8) vs 2U (1-4), P=0.0001]. Crude 30-day mortality was 19.3% vs 17.0% (P=0.60). After matching, major bleeding remained significantly more common in DAPT patients, 51.3% vs 39.3% [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05-2.51; P=0.028], but mortality did not significantly differ (OR 0.88, 95% CI 0.51-1.50; P=0.63). Major bleeding was associated with increased 30-day mortality (adjusted OR 2.44, 95% CI 1.72-3.46; P<0.0001).DAPT prior to acute aortic dissection repair was associated with increased bleeding and transfusions but not with mortality. Major bleeding per se was associated with a significantly increased mortality. Correct diagnosis is important to avoid DAPT and thereby reduce bleeding risk, but ongoing DAPT should not delay surgery.
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23.
  • Helgason, Dadi, et al. (författare)
  • Acute Kidney Injury Following Acute Repair of Type A Aortic Dissection.
  • 2021
  • Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 111:4, s. 1292-1298
  • 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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24.
  • Hultgren, Karin, et al. (författare)
  • Acute coronary angiography after coronary artery bypass grafting.
  • 2016
  • Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 50:2, s. 123-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Coronary angiography is the golden standard when myocardial ischemia after CABG occurs. We summarize our experience of acute coronary angiography after CABG. Design All 4446 patients (mean age 68±9 years, 22% women) who underwent CABG 2007 to 2012 were included in this retrospective observational study. Incidence, indications, findings, measures of acute angiography after CABG was assessed. Outcome variables were compared between patients who underwent angiography and those who did not. Results Eighty-seven patients (2%) underwent acute coronary angiography. Patients undergoing angiography had ECG changes (92%), echocardiographic alterations (48%), hemodynamic instability (28%), angina (15%), and/or arrhythmia (13%). Positive findings were detected in 69% of the cases. Only ECG changes as indication for angiography had a moderate association with positive findings, but the precision increased if other sign(s) of ischemia were present. Thirty-day mortality (7% versus 2%, p=0.002) was higher and long-term-cumulative survival lower (77% versus 87% at five years, p=0.043) in angiography patients. Conclusions Acute angiography is a rare event after CABG. Postoperative myocardial ischemia leading to acute coronary angiography is associated with increased short-term and long-term mortality.
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25.
  • Jinton, Helen, 1996, et al. (författare)
  • Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest
  • 2024
  • Ingår i: SCIENTIFIC REPORTS. - 2045-2322. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1 alpha. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.
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26.
  • Johansson-Synnergren, Mats, 1968, et al. (författare)
  • Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study.
  • 2004
  • Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 38:1, s. 53-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE--Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN--Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS--C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION--OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.
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27.
  • Jonsson, Marianne, 1962, et al. (författare)
  • Novel 3D culture system with similarities to the human heart for studies of the cardiac stem cell niche.
  • 2010
  • Ingår i: Regenerative medicine. - : Future Medicine Ltd. - 1746-076X .- 1746-0751. ; 5:5, s. 725-36
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The aim of this study was to develop a 3D culture system with similarities to the human heart, which was suitable for studies of adult cardiac stem or progenitor cells. MATERIALS & METHODS: Dissociated cells from human cardiac biopsies were placed in high-density pellet cultures and cultured for up to 6 weeks. Gene and protein expressions, analyzed by quantitative real-time PCR and immunohistochemistry, and morphology were studied in early and late pellets. RESULTS: Cells cultured in the 3D model showed similarities to human cardiac tissue. Moreover, markers for cardiac stem and progenitor cells were also detected after 6 weeks of culture, in addition to markers for signaling pathways active in stem cell niche regulation. CONCLUSIONS: The described 3D culture model could be a valuable tool when studying the influence of different compounds on proliferation and differentiation processes in cardiac stem or progenitor cells in cardiac regenerative research.
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28.
  • Labaf, Ashkan, et al. (författare)
  • Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: A nationwide population-based study
  • 2016
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 181, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Risk factors of stroke/thromboembolism (TE) and major bleeding, and incidence of these events in specific age categories in warfarin-treated patients with mechanical heart valves (MHV) are uncertain. Our objective was to calculate event rates in specific age categories and identify risk factors for adverse events. Methods and results We identified 4,810 treatment periods with MHV between January 2006 and December 2011 in the Auricula and Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. There were 3,751 treatment periods with aortic valve replacements (AVR) and 866 with mitral valve replacements (MVR). Median follow-up time was 4.5 years (IQR, 1.5-6.0). Time in therapeutic range with warfarin for patients with AVR was 74.2% for international normalized ratio of 2.0 to 3.0, with 72% of the patients having this target range. Rate of stroke/TE for AVR and MVR was 1.3 and 1.6 per 100 patient years, respectively (P=.20). The rate of first major bleeding was 2.6 and 3.9 per 100 patient years with AVR and MVR, respectively (P<.001). By multivariate analysis for AVR, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03 per year) and previous stroke (HR, 2.4; 95% CI, 1.7-3.5) emerged as independent risk factors for stroke/TE. Heart failure (HR, 0.9; 95% CI, 0.6-1.4) and atrial fibrillation (HR, 1.0; 95% CI, 0.7-1.4) were not associated to stroke/TE. For major bleeding events, age (HR, 1.02; 95% CI, 1.01-1.03 per year) and previous major bleeding (HR, 2.5; 95% CI, 1.9-3.3) emerged as independent risk factors for AVR. Conclusions In a nationwide cohort study with MHV and high time in therapeutic range, heart failure and atrial fibrillation did not appear as risk factors of stroke/TE. © 2016
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29.
  • Lachonius, Maria, 1962, et al. (författare)
  • Patients' motivation to undergo transcatheter aortic valve replacement. A phenomenological hermeneutic study.
  • 2023
  • Ingår i: International journal of older people nursing. - : Wiley. - 1748-3743 .- 1748-3735. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Aortic stenosis is the most common valvular disease, and its prevalence is increasing due to the ageing population. Transcatheter aortic valve replacement (TAVR) is the recommended method when treating frail, older patients. Knowledge of what motivates older patients to undergo TAVR is important, in order to meet patients' expectations.The study aimed to explore the meaning of older patients' motivation to undergo TAVR.The design was a qualitative study, analysed using a phenomenological hermeneutic approach. In-depth, semi-structured interviews with open-ended questions were conducted. Participants were selected from a specialist cardiology clinic in Sweden. Eighteen patients, six women and twelve men, aged 66-92, were recruited.The analysis showed that patients who had agreed to undergo TAVR were deeply affected by their body's failure. Before the TAVR procedure, the participants were limited in their daily activities and experienced that their life was on hold. They experienced that they were barely existing. They were aware of their life-threatening condition and were forced to confront death. Yet despite an advanced age, they still had considerable zest for life. It was very important to them to remain independent in everyday life, and fear of becoming dependent had a strong impact on their motivations for undergoing TAVR.Older patients' motivations to undergo TAVR are strongly influenced by their fear of being dependent on others and their zest for life. Health care professionals need to support these patients in setting realistic and personalised goals.Person-centered care actions could facilitate patients' involvement in the decision about TAVR and strenghten patients' beliefs in their own capabilities, before and after TAVR.
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30.
  • Lindholm, Lena, et al. (författare)
  • A closed perfusion system with heparin coating and centrifugal pump improves cardiopulmonary bypass biocompatibility in elderly patients.
  • 2004
  • Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 78:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory and hemostatic activation, which may contribute to postoperative complications. Our aim was to compare the inflammatory response, coagulation, and fibrinolytic activation between two different perfusion systems: one theoretically more biocompatible with a closed-circuit, complete heparin coating, and a centrifugal pump, and one conventional system with uncoated circuit, roller pump, and a hard-shell venous reservoir. METHODS: Forty-one elderly patients (mean age, 73 +/- 1 years, 66% men) undergoing coronary artery bypass grafting or aortic valve replacement were included in a prospective, randomized study. Plasma concentrations of complement factors (C3a, C4d, Bb, and sC5b-9), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-8), granulocyte degradation products (polymorphonuclear elastase), and markers of coagulation (thrombin-antithrombin) and fibrinolysis (D-dimer, tissue plasminogen activator antigen and tissue plasminogen activator-plasminogen activator inhibitor-1 complex) were measured preoperatively, at bypass during rewarming (35 degrees C), 60 minutes after bypass, and on day 1 after surgery. RESULTS: The mean concentrations of C3a (-39%; p = 0.008), Bb (-38%; p < 0.001), sC5b-9 (-70%; p < 0.001), interleukin-8 (-60%; p = 0.009), polymorphonuclear-elastase (-55%; p < 0.003), and tissue plasminogen activator antigen (-51%; p = 0.012) were all significantly lower in the biocompatible group during rewarming. Sixty minutes after bypass, the mean concentrations of sC5b-9 (-39%; p = 0.006) and polymorphonuclear-elastase (-55%; p < 0.001) were lower in the biocompatible group. CONCLUSIONS: The results suggest that a closed perfusion system with a heparin-coated circuit and a centrifugal pump may improve cardiopulmonary bypass biocompatibility in elderly cardiac surgery patients in comparison with a conventional system.
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31.
  • Lindholm, Lena, et al. (författare)
  • Regional oxygenation and systemic inflammatory response during cardiopulmonary bypass: influence of temperature and blood flow variations.
  • 2003
  • Ingår i: Journal of cardiothoracic and vascular anesthesia. - : Elsevier BV. - 1053-0770. ; 17:2, s. 182-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the role of target temperature (28 degrees or 34 degrees C) in cardiac surgery on regional oxygenation during hypothermia and rewarming and systemic inflammatory response. DESIGN: Prospective, controlled, and randomized clinical study. SETTING: University hospital. PARTICIPANTS: Elderly patients (mean age 70 +/- 2 years) with acquired heart disease with an anticipated bypass time exceeding 120 minutes (n = 30). INTERVENTIONS: The patients were cooled to either 28 degrees C (n = 15) or 34 degrees C (n = 15). At hypothermia, bypass blood flow was reduced twice from full flow (2.4 L/min/m(2) body surface area [BSA]) to 2.0 L/min/m(2). MEASUREMENTS AND MAIN RESULTS: Hepatic and jugular venous oxygen tension and saturation were higher at 28 degrees C than at 34 degrees C. In comparison with the preoperative values, at 28 degrees C hepatic venous values were higher; whereas at 34 degrees C, they were lower. The reduction of pump blood flow during hypothermia, from 2.4 to 2.0 L/min/m(2)was accompanied by reductions of central, jugular, and hepatic oxygenation at both target temperatures. During rewarming, central and regional venous oxygenation decreased irrespective of the preceding temperature. The decrease was most pronounced in hepatic venous blood, with the lowest individual values <10%. Serum concentrations of C3a and IL-6 increased during hypothermia and increased further during rewarming irrespective of the preceding temperature. CONCLUSION: During cardiopulmonary bypass, hypothermia at 28 degrees C increases regional and central venous oxygenation better than at 34 degrees C. In contrast, venous oxygenation decreases during rewarming irrespective of the preceding temperature. No significant difference in the systemic inflammatory response associated with target temperature was detected.
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32.
  • Nozohoor, Shahab, et al. (författare)
  • ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection
  • 2020
  • Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:2, s. 124-129
  • 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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33.
  • Oudin Åström, Daniel, et al. (författare)
  • Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics
  • 2022
  • Ingår i: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9880 .- 1654-9716. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (<=-5 degrees C) and hot temperatures (>= 21 degrees C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
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34.
  • Pan, E., et al. (författare)
  • Low rate of reoperations after acute type A aortic dissection repair from The Nordic Consortium Registry
  • 2018
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 156:3, s. 939-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe the relationship between the extent of primary aortic repair and the incidence of reoperations after surgery for type A aortic dissection. Methods: A retrospective cohort of 1159 patients treated for type A aortic dissection at eight Nordic low-to medium-sized cardiothoracic centers from 2005 to 2014. Data were gathered from patient records and national registries. Patients were separately divided into 3 groups according to the distal anastomoses technique (ascending aorta [n = 791], hemiarch [n = 247], and total arch [n = 66]), and into 2 groups for proximal repair (aortic root replacement [n = 285] and supracoronary repair [n = 832]). Freedom from reoperation was estimated with cumulative incidence survival and Fine-Gray competing risk regression model was used to identify independent risk factors for reoperation. Results: The median follow-up was 2.7 years (range, 0-10 years). Altogether 51 out of 911 patients underwent reoperation. Freedom from distal reoperation at 5 years was 96.9%, with no significant difference between the groups (P = .22). Freedom from proximal reoperation at 5 years was 97.8%, with no difference between the groups (P = .84). Neither DeBakey classification nor the extent of proximal or distal repair predicted freedom from a later reoperation. The only independent risk factor associated with a later proximal reoperation was a history of connective tissue disease. Conclusions: Type A aortic dissection repair in low-to medium-volume centers was associated with a low reoperation rate and satisfactory midterm survival. The extent of the primary repair had no significant influence on reoperation rate or midterm survival.
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35.
  • Radulovic, Vladimir, 1969, et al. (författare)
  • Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.
  • 2012
  • Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 130:5, s. 769-774
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. MATERIAL AND METHODS: Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2h and 24h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. RESULTS: Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. CONCLUSIONS: A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.
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36.
  • Rezk, Mary, et al. (författare)
  • Clinical Course of Postoperative Atrial Fibrillation After Cardiac Surgery and Long-Term Outcome.
  • 2022
  • Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 114:6, s. 2209-2215
  • Tidskriftsartikel (refereegranskat)abstract
    • New-onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with worse short- and long-term outcome. Although the clinical presentation of POAF varies substantially, almost all studies model it with a dichotomous yes/no variable. We explored potential associations between the clinical course of POAF and long-term outcome.This retrospective observational single-center study included 6435 CABG and/or valve patients between 2010 and 2018. POAF patients were grouped into 1) spontaneous/pharmacological conversion to sinus rhythm, 2) sinus rhythm after electrical cardioversion, and 3) sustained atrial fibrillation (AF) at discharge. Multivariable Cox regression models adjusted for age, sex, type of surgery, co-morbidities, and early-initiated oral anticoagulation were used to study associations between the clinical course of POAF and long-term risk for mortality, ischemic stroke, thromboembolic events, heart failure hospitalization, and major bleeding. Median follow-up time was 3.8 years (range: 0-8.3 years).POAF occurred in 2172 (33.8%) of the patients, 94.9% of whom converted to sinus rhythm before discharge. Of these, 73.6% converted spontaneously or with pharmacological treatment, and 26.4% after electrical cardioversion. Both sustained AF and electrical cardioversion were independently associated with an increased long-term risk for heart failure (adjusted hazard ratio for sustained AF at discharge: 2.55, 95%CI: 1.65-3.93, p<0.001; for electrical cardioversion: 1.28, 95%CI: 1.00-1.65, p=0.047), but not with increased long-term risk for death, thromboembolic complications, or bleedings.A more complicated POAF course is associated with increased long-term risk for heart failure hospitalization, but not for all-cause mortality or thromboembolic complications.
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37.
  • Roos, H., et al. (författare)
  • Re-interventions after endovascular aortic repair for infrarenal abdominal aneurysms: a retrospective cohort study
  • 2016
  • Ingår i: Bmc Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early morbidity and mortality are generally lower after endovascular aortic repair (EVAR), than after open repair but re-interventions and late complications are more common. The aim of the present study was to make a detailed description of re-interventions after EVAR-including incidence, indications, procedures, and outcome-with special reference to non-access-related re-interventions. Methods: This is a retrospective single-center cohort study of re-interventions after standard EVAR with special reference to non-access-related re-interventions. Consecutive patients (n = 405) treated with standard EVAR for non-ruptured (n = 337) or ruptured (n = 68) infrarenal aneurysms between 2005 and 2013 were analysed. Median follow-up was 29 months (range 0-108). Results: Eighty-nine patients (22 %) underwent 113 re-interventions during follow-up. Twenty-seven patients (7 %) had 28 access related re-intervention, 65 patients (16 %) had 85 non-access related reinterventions. Non-access related re-interventions were more common in ruptured aneurysms than in unruptured aneurysms (22 vs. 15 %, p = 0.002). The most frequent indications were endoleak type I (n = 19), type II (n = 21), or type III (n = 5); stent graft migration (n = 9); and thrombosis (n = 14). The most frequent procedures were embolization of endoleak type II (n = 21), additional iliac stent graft (n = 19), proximal extension (n = 12), thrombolysis (n = 8), iliac limb bare-metal stenting (n = 6), and stent graft relining (n = 7). Endovascular technique was used in 83 % of re-interventions. Thirty-day mortality after non-access-related re-interventions was 15 % when initiated from symptoms (rupture or infection) and 0 % when initiated from follow-up findings (p = 0.014). Cumulative survival five years after EVAR was 72 % in patients with a re-intervention and 59 % in patients without (p = 0.21). Conclusions: Non-access-related re-intervention rates are still considerable after EVAR and more frequent after ruptured aneurysms. Endoleak embolization is the most frequent procedure, followed by additional iliac stent grafts. Outcomes after re-interventions are generally good, except when initiated by rupture or infection.
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38.
  • Sandstedt, Joakim, et al. (författare)
  • C-kit+ CD45- cells found in the adult human heart represent a population of endothelial progenitor cells.
  • 2010
  • Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 105:4, s. 545-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Although numerous reports support the existence of stem cells in the adult heart, few studies have been conducted using human cardiac tissue. Therefore, cells from human cardiac atrial biopsies were analyzed regarding progenitor properties. Expression of stem cell markers was analyzed using fluorescence-activated cell sorting. This identified a small population of C-kit+ cells, which could be further subdivided based on expression of CD45. The C-kit+ CD45+ population was determined to be of mast cell identity, while the C-kit+ CD45- population expressed mRNA of the endothelial lineage. Since the number of cells obtainable from biopsies was limited, a comparison between directly isolated and monolayer and explant cultured cells, respectively, was carried out. While both cultures retained a small population of mast cells, only monolayer culture produced a stable and relatively high percentage of C-kit+ CD45- cells. This population was found to co-express endothelial progenitor cell markers such as CD31, CD34, CXCR4, and FLK-1. The mRNA expression profile was similar to the one from directly isolated cells. When sorted cells were cultured in endothelial differentiation medium, the C-kit+ CD45- population retained its expression of endothelial markers to a large extent, but downregulated progenitor markers, indicating further differentiation into endothelial cells. We have confirmed that the human cardiac atrium contains a small C-kit+ CD45- population expressing markers commonly found on endothelial progenitor cells. The existence of an endothelial progenitor population within the heart might have future implications for developing methods of inducing neovascularization after myocardial infarction.
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39.
  • Sandstedt, Joakim, et al. (författare)
  • Human C-kit+CD45- cardiac stem cells are heterogeneous and display both cardiac and endothelial commitment by single-cell qPCR analysis.
  • 2014
  • Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 443:1, s. 234-238
  • Tidskriftsartikel (refereegranskat)abstract
    • C-kit expressing cardiac stem cells have been described as multipotent. We have previously identified human cardiac C-kit+CD45- cells, but only found evidence of endothelial commitment. A small cardiac committed subpopulation within the C-kit+CD45- population might however be present. To investigate this at single-cell level, right and left atrial biopsies were dissociated and analyzed by FACS. Only right atrial biopsies contained a clearly distinguishable C-kit+CD45- population, which was single-cell sorted for qPCR. A minor portion of the sorted cells (1.1%) expressed early cardiac gene NKX2.5 while most of the cells (81%) expressed late endothelial gene VWF. VWF- cells were analyzed for a wider panel of genes. One group of these cells expressed endothelial genes (FLK-1, CD31) while another group expressed late cardiac genes (TNNT2, ACTC1). In conclusion, human C-kit+CD45- cells were predominantly localized to the right atrium. While most of these cells expressed endothelial genes, a minor portion expressed cardiac genes.
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40.
  • Sandstedt, Joakim, et al. (författare)
  • Left atrium of the human adult heart contains a population of side population cells.
  • 2012
  • Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 107:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac "side population" (SP) cells have previously been found to differentiate into both endothelial cells and cardiomyocytes in mice and rats, but there are no data on SP cells in the human adult heart. Therefore, human cardiac atrial biopsies were dissociated, stained for SP cells and analyzed with FACS. Identified cell populations were analyzed for gene expression by quantitative real-time PCR and subjected to in vitro differentiation. Only biopsies from the left atrium contained a clearly distinguishable population of SP cells (0.22±0.08%). The SP population was reduced by co-incubation with MDR1 inhibitor Verapamil, while the ABCG2 inhibitor FTC failed to decrease the number of SP cells. When the gene expression was analyzed, SP cells were found to express significantly more MDR1 than non-SP cells. For ABCG2, there was no detectable difference. SP cells also expressed more of the stem cell-associated markers C-KIT and OCT-4 than non-SP cells. On the other hand, no significant difference in the expression of endothelial and cardiac genes could be detected. SP cells were further subdivided based on CD45 expression. The CD45-SP population showed evidence of endothelial commitment at gene expression level. In conclusion, the results show that a SP population of cells is present also in the human adult heart.
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41.
  • Sandstedt, Joakim, et al. (författare)
  • SSEA-4+ CD34- Cells in the Adult Human Heart Show the Molecular Characteristics of a Novel Cardiomyocyte Progenitor Population.
  • 2014
  • Ingår i: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 199:2-3, s. 103-116
  • Tidskriftsartikel (refereegranskat)abstract
    • Stage-specific embryonic antigen (SSEA) expression is used to describe the differentiation state of an embryonic stem cell (ESC). In human ESCs, SSEA-3 and SSEA-4 are highly expressed in undifferentiated cells and downregulated upon differentiation. SSEA-4 has also been described as a marker for adult stem cells in various tissues, including human neonatal cardiac tissue. However, there is currently little data on the expression of SSEAs in human adult cardiac tissue. We obtained right and left atrial biopsies from patients undergoing cardiac surgery. These were dissociated, stained for SSEAs and other cardiac stem cell markers and analyzed by flow cytometry. Directly isolated cells expressed variable levels of SSEA-1, SSEA-3 and SSEA-4. The SSEA-1+ population was established as contaminating hematopoietic cells. The SSEA-4+ population, on the other hand, could be subdivided based on the endothelial progenitor marker CD34. The SSEA-4+ CD34- population in the right atrium had a high gene expression of both early (TBX5, NKX2.5) and late (TNNT2) cardiomyocyte markers. The SSEA-4+ CD34+ population, on the other hand, overlapped with previously described C-kit+ CD45- cardiac stem cells. Primary monolayer-cultured cells retained expression of SSEAs while the cardiomyogenic specification in the SSEA-4+ CD34- population was lost. In tissue sections, SSEA-4+ cells could be identified both within and outside the myocardium. Within the myocardium, some SSEA-4+ cells coexpressed cardiomyogenic markers. In conclusion, the results show that the adult human heart expresses SSEAs and that there is a subpopulation of SSEA-4+ CD34- cells that show features of a cardiomyocyte progenitor population. © 2014 S. Karger AG, Basel.
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42.
  • Sandstedt, Mikael, 1990, et al. (författare)
  • Intracellular flow cytometry may be combined with good quality and high sensitivity RT-qPCR analysis.
  • 2015
  • Ingår i: Cytometry. Part A : the journal of the International Society for Analytical Cytology. - : Wiley. - 1552-4930. ; 87:12, s. 1079-1089
  • Tidskriftsartikel (refereegranskat)abstract
    • Flow cytometry (FCM) has become a well-established method for analysis of both intracellular and cell-surface proteins, while quantitative RT-PCR (RT-qPCR) is used to determine gene expression with high sensitivity and specificity. Combining these two methods would be of great value. The effects of intracellular staining on RNA integrity and RT-qPCR sensitivity and quality have not, however, been fully examined. We, therefore, intended to assess these effects further. Cells from the human lung cancer cell line A549 were fixed, permeabilized and sorted by FCM. Sorted cells were analyzed using RT-qPCR. RNA integrity was determined by RNA quality indicator analysis. A549 cells were then mixed with cells of the mouse cardiomyocyte cell line HL-1. A549 cells were identified by the cell surface marker ABCG2, while HL-1 cells were identified by intracellular cTnT. Cells were sorted and analyzed by RT-qPCR. Finally, cell cultures from human atrial biopsies were used to evaluate the effects of fixation and permeabilization on RT-qPCR analysis of nonimmortalized cells stored prior to analysis by FCM. A large amount of RNA could be extracted even when cells had been fixed and permeabilized. Permeabilization resulted in increased RNA degradation and a moderate decrease in RT-qPCR sensitivity. Gene expression levels were also affected to a moderate extent. Sorted populations from the mixed A549 and HL-1 cell samples showed gene expression patterns that corresponded to FCM data. When samples were stored before FCM sorting, the RT-qPCR analysis could still be performed with high sensitivity and quality. In summary, our results show that intracellular FCM may be performed with only minor impairment of the RT-qPCR sensitivity and quality when analyzing sorted cells; however, these effects should be considered when comparing RT-qPCR data of not fixed samples with those of fixed and permeabilized samples. © 2015 International Society for Advancement of Cytometry.
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43.
  • Sandstedt, Mikael, 1990, et al. (författare)
  • Regional transcriptomic profiling reveals immune system enrichment in nonfailing atria as well as all chambers of the failing human heart
  • 2023
  • Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 325:6, s. H1430-H1445
  • Tidskriftsartikel (refereegranskat)abstract
    • The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathologic remodeling, resulting in heart failure. Few previous studies have, however, 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. Compared to nonfailing ventricles, the transcriptional pattern of nonfailing atria was enriched for a large number of gene sets associated with cardiogenesis, the immune system and bone morphogenetic protein (BMP), transforming growth factor beta (TGF beta), MAPK/JNK and Wnt signaling. Differences between failing and nonfailing hearts were also determined. The transcriptional pattern of failing atria was distinct compared to that of nonfailing atria and enriched for gene sets associated with the innate and adaptive immune system, TGF beta/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.
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44.
  •  
45.
  • Sjölin, Jacob, et al. (författare)
  • Expression of Stem Cell Niche-Related Biomarkers at the Base of the Human Tricuspid Valve
  • 2023
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 32:5-6, s. 140-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cell niches have been thoroughly investigated in tissue with high regenerative capacity but not in tissues where cell turnover is slow, such as the human heart. The left AtrioVentricular junction (AVj), the base of the mitral valve, has previously been proposed as a niche region for cardiac progenitors in the adult human heart. In the present study, we explore the right side of the human heart, the base of the tricuspid valve, to investigate the potential of this region as a progenitor niche. Paired biopsies from explanted human hearts were collected from multi-organ donors (N = 12). The lateral side of the AVj, right atria (RA), and right ventricle (RV) were compared for the expression of stem cell niche-related biomarkers using RNA sequencing. Gene expression data indicated upregulation of genes related to embryonic development and extracellular matrix (ECM) composition in the proposed niche region, that is, the AVj. In addition, immunohistochemistry showed high expression of the fetal cardiac markers MDR1, SSEA4, and WT1 within the same region. Nuclear expression of HIF1 alpha was detected suggesting hypoxia. Rare cells were found with the co-staining of the proliferation marker PCNA and Ki67 with cardiomyocyte nuclei marker PCM1 and cardiac Troponin T (cTnT), indicating proliferation of small cardiomyocytes. WT1+/cTnT+ and SSEA4+/cTnT+ cells were also found, suggesting cardiomyocyte-specific progenitors. The expression of the stem cell markers gradually decreased with distance from the tricuspid valve. No expression of these markers was observed in the RV tissue. In summary, the base of the tricuspid valve is an ECM-rich region containing cells with expression of several stem cell niche-associated markers. Co-expression of stem cell markers with cTnT indicates cardiomyocyte-specific progenitors. We previously reported similar data from the base of the mitral valve and thus propose that human adult cardiomyocyte progenitors reside around both atrioventricular valves.
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46.
  • Synnergren, Jane, et al. (författare)
  • Transcriptional sex and regional differences in paired human atrial and ventricular cardiac biopsies collected in vivo
  • 2020
  • Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 52:2, s. 110-120
  • 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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47.
  • Söderlund, Fredrik, et al. (författare)
  • In vitro anti-platelet potency of ticagrelor in blood samples from infants and children.
  • 2015
  • Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 136:3, s. 620-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent P2Y12 receptor, is currently approved for treating adults with acute coronary syndrome. The effect of ticagrelor in children has not been explored. As a first step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in blood samples from children of different age is different as compared with in blood samples from adults.
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48.
  • Taha, Amar, 1978, et al. (författare)
  • Cardiopulmonary bypass management and risk of new-onset atrial fibrillation after cardiac surgery.
  • 2023
  • Ingår i: Interdisciplinary cardiovascular and thoracic surgery. - 2753-670X. ; 37:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiopulmonary bypass management may potentially play a role in the development of new-onset atrial fibrillation after cardiac surgery. The aim of this study was to explore this potential association.Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016-2020 were included in an observational single-centre study. Data collected from the SWEDEHEART Registry, and a local Cardiopulmonary bypass database were merged. Associations between individual cardiopulmonary bypass variables (Cardiopulmonary bypass and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature, and haematocrit) and new-onset atrial fibrillation were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities, and surgical procedure.Out of 1,999 patients, 758 (37.9%) developed new-onset atrial fibrillation. Patients with new-onset postoperative atrial fibrillation were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores, and more often underwent valve surgery. Longer cardiopulmonary bypass time (adjusted odds ratio (aOR) 1.05 per 10min (95% confidence interval (CI) 1.01-1.08); p=0.008) and higher flow index (aOR 1.21 per 0.2L/m2 (95% CI 1.02-1.42); p=0.026) were associated with an increased risk for new-onset atrial fibrillation, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses.Cardiopulmonary bypass management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset atrial fibrillation after cardiac surgery.
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49.
  • Taha, Amar, 1978, et al. (författare)
  • New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.
  • 2021
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 10:1
  • 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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50.
  • Taha, Amar, 1978, et al. (författare)
  • Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.
  • 2022
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.
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