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1.	2019 Tidskriftsartikel (refereegranskat)
2.	Adler, Eric D., et al. (författare) Improving risk prediction in heart failure using machine learning 2020 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:1, s. 139-147 Tidskriftsartikel (refereegranskat)abstract Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
3.	Amisten, Stefan, et al. (författare) Gene expression profiling for the identification of G-protein coupled receptors in human platelets 2008 Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 122:1, s. 47-57 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION AND MATERIALS AND METHODS: G-protein coupled receptors (GPCRs) play an important role in platelet aggregation. To identify new platelet GPCRs, a platelet gene expression profile was generated and validated using quantitative real-time PCR. RESULTS: In total, mRNA of 28 GPCR genes was detected in human platelets. The 12 most abundant platelet GPCR transcripts were: thrombin receptor PAR1 (1865+/-178%), ADP receptor P2Y(12) (459+/-88%), succinate receptor 1 (257+/-48%), ADP receptor P2Y(1) (100%), orphan P2RY(10) (68.2+/-3.3%), lysophosphatidic acid receptors GPR23 (48.2+/-11%) and GPR92 (26.1+/-3.3%), adrenergic receptor alpha(2A) (18.4+/-4.4%), orphan EBI2 (6.31+/-0.42), adenosine receptors A(2A) (2.94+/-0.24%) and A(2B) (2.88+/-0.16%) and lysophosphatidic acid receptor LPA(1) (2.59+/-0.39%) (% relative to the chosen calibrator P2Y(1)). A surprising G-protein coupled receptor redundancy was found: two ADP receptors (P2Y(1) and P2Y(12)), three adenosine receptors (A(2A), A(2B), and A(1)), four lysophosphatidic acid receptors (LPA(1), LPA(3), GPR23 and GPR92), two l-glutamate receptors (mGlu(3) and mGlu(4)) and two serotonin receptors (5-HT(1F) and 5-HT(4)). The adenosine receptor A(2B) gene expression was validated with protein expression and functional studies. Western blot confirmed A(2B) receptor protein expression and platelet flow cytometry demonstrated inhibition of the effect of NECA by the adenosine A(2B)-antagonist MRS1754. CONCLUSIONS: We have detected several GPCRs not previously known to be expressed in platelets, including a functional adenosine A(2B) receptor. The findings could improve our understanding of platelet aggregation and provide new targets for drug development.
4.	Amisten, Stefan, et al. (författare) The P2Y(13) Met-158-Thr Polymorphism, Which Is in Linkage Disequilibrium with the P2Y(12) Locus, Is Not Associated with Acute Myocardial Infarction. 2008 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: The aims of this study were to investigate (1) if P2Y(12) polymorphisms defining the P2Y(12) H2 allele are associated with any other SNPs that may explain the previously reported association with increased ADP induced platelet activation and association with peripheral arterial disease and coronary artery disease and (2) if such variants are associated with acute myocardial infarction (AMI) or classical risk factors for AMI. METHODS AND RESULTS: The P2Y(13) Met-158-Thr polymorphism was found to be in linkage disequilibrium (LD) with the P2Y(12) H2 haplotype (all examined SNPs: D' = 1.0, r(2) = 0.936-1.0), defining a novel P2Y(12) H2/P2Y(13) Thr-158 haplotype. Genotyping of an AMI case control population (n = 1244 cases, 2488 controls) revealed no association of the P2Y(13) Thr-158 allele with AMI (OR = 0.96, 95% C.I. 0.82-1.12, P = 0.63). Also, no differences between the genotype frequencies of P2Y(13) Met-158-Met and Met-158-Thr/Thr-158-Thr were seen in AMI case-control subpopulations (early onset AMI OR = 1.06, 95% C.I. 0.85-1.31, P = 0.62); family history of AMI (OR = 0.98, 95% C.I. 0.78-1.22, P = 0.83) nor in early onset AMIs with family history of AMI (OR = 1.0, 95% C.I. 0.74-1.36, P = 1.0). Genotyping of the P2Y(13) Met-158-Thr polymorphism in a population based sample (n = 6055) revealed no association with cardiovascular risk factors. In addition, the P2Y(13) Met-158-Thr polymorphism was genotyped in a diabetes case-control population, and associations were found neither with DM nor with any examined DM risk factors. CONCLUSION GENOTYPING: The P2Y(13) Met-158-Thr polymorphism is in tight LD with the P2Y(12) locus but is not associated with AMI or classical cardiovascular risk factors.
5.	Ammirati, Enrico, et al. (författare) Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device : Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA) 2021 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 324 Tidskriftsartikel (refereegranskat)abstract Background: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. Methods: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. Results: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. Conclusions: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
6.	Angerås, Oskar, et al. (författare) Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population based cohort study. 2015 Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; :nov 12, s. 1-24 Tidskriftsartikel (refereegranskat)abstract New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS.
7.	Bergman, Elin, et al. (författare) Dabigatran in clinical practice - One-year experience at Skåne University Hospital. 2013 Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 132:2, s. 316-317 Tidskriftsartikel (refereegranskat)
8.	Bobbio, Emanuele, et al. (författare) Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden. 2022 Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 9:4, s. 2654-2663 Tidskriftsartikel (refereegranskat)abstract Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF.All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49±13years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [β coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P<0.001], followed by lower mean arterial pressure (MAP) (β coefficient 0.29; 95% CI 0.14-0.37; P<0.001), and finally reduced cardiac index (β coefficient 3.51; 95% CI 2.14-4.84; P<0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output.In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.
9.	Bollano, Entela, 1970, et al. (författare) Temporal trends in characteristics and outcome of heart failure patients with and without significant coronary artery disease 2022 Ingår i: ESC Heart Failure. - Oxford, United Kingdom : John Wiley & Sons. - 2055-5822. ; 9:3, s. 1812-1822 Tidskriftsartikel (refereegranskat)abstract Aims: Ischaemic coronary artery disease (CAD) remains the leading cause of mortality globally due to sudden death and heart failure (HF). Invasive coronary angiography (CAG) is the gold standard for evaluating the presence and severity of CAD. Our objective was to assess temporal trends in CAG utilization, patient characteristics, and prognosis in HF patients undergoing CAG at a national level.Methods and results: We used data from the Swedish Coronary Angiography and Angioplasty Registry. Data on all patients undergoing CAG for HF indication in Sweden between 2000 and 2018 were collected and analysed. Long-term survival was estimated with multivariable Cox proportional hazards regression adjusted for differences in patient characteristics. In total, 22 457 patients (73% men) with mean age 64.2 ± 11.3 years were included in the study. The patients were increasingly older with more comorbidities over time. The number of CAG specifically for HF indication increased by 5.5% per calendar year (P < 0.001). No such increase was seen for indications angina pectoris and ST-elevation myocardial infarction. A normal CAG or non-obstructive CAD was reported in 63.2% (HF-NCAD), and 36.8% had >50% diameter stenosis in one or more coronary arteries (HF-CAD). The median follow-up time was 3.6 years in HF-CAD and 5 years in HF-NCAD. Age and sex-adjusted survival improved linearly by 1.3% per calendar year in all patients. Compared with HF-NCAD, long-term mortality was higher in HF-CAD patients. The risk of death increased with the increasing severity of CAD. Compared with HF-NCAD, the risk estimate in patients with a single-vessel disease was higher [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.20–1.41; P < 0.001], a multivessel disease without the involvement of left main coronary artery (HR 1.72; 95% CI 1.58–1.88; P < 0.001), and with left main disease (HR 2.02; 95% CI 1.88–2.18; P < 0.001). The number of HF patients undergoing revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) increased by 7.5% (P < 0.001) per calendar year. The majority (53.4%) of HF-CAD patients were treated medically, while a minority (46.6%) were referred for revascularization with PCI or CABG. Compared with patients treated with PCI, the proportion of patients treated medically or with CABG decreased substantially (P < 0.001).Conclusions: Over 18 years, the number of patients with HF undergoing CAG has increased substantially. Expanded utilization of CAG increased the number of HF patients treated with percutaneous coronary intervention and coronary artery bypass surgery. Long-term survival improved in all HF patients despite a steady increase of elderly patients with comorbidities.
10.	Braun, Oscar, et al. (författare) Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome. 2015 Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 135:1, s. 26-30 Tidskriftsartikel (refereegranskat)abstract Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS).
11.	Braun, Oscar, et al. (författare) Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways 2013 Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1223-1231 Tidskriftsartikel (refereegranskat)abstract Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C192 allele has been associated with impaired response; conflicting results have been reported for CYP2C1917, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = 17 carriers; extensive metabolisers [EM] = 1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow (R) P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PR!) after 14 days of maintenance dosing. Clopi-, dogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but notABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
12.	Braun, Oscar (författare) Experimental and Clinical Studies on Platelet Receptors in Cardiovascular Disease 2007 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The crucial role of platelets in maintaining primary hemostais has been evident for a long time and there is now also mounting evidence for their involvement in inflammation. In combination with aspirin, inhibition of the platelet P2Y12 ADP receptor with clopidogrel has become a cornerstone in the antiplatelet in acute coronary syndromes. Recently, several studies have indicated that a considerable number of patients treated with clopidogrel show poor responsiveness to the drug. In this thesis we investigate possible variables explaining the mechanisms behind variation to clopidogrel. We also investigate the effects of a novel P2Y12 receptor antagonist, prasugrel, in comparison to clopidogrel. In the last paper we investigate the mechanisms behind platelet-endothelial cell interactions in a mouse model of arterial inflammation. To study platelet function we mainly used flow cytometry based techniques. We used real-time RT-PCR and quantitative western blots to study mRNA and protein expression levels in human platelets. To study platelet interactions in vivo in mice we used fluorescent intravital microscopy. We could confirm the expression of three P2 receptors in human platelets and exclude expression of additional P2 receptors. In hyperactive platelets from patients with peripheral arterial disease we could not detect increased P2 receptor expression as compared to healthy controls. In a subsequent study we could correlate decreased response to clopidogrel to increased protein expression of the P2Y12 receptor in patients with coronary artery disease. We could conclude that prasugrel inhibits several markers of platelet activation and the formation of platelet-leukocyte aggregates more efficiently than clopidogrel. Furthermore, in a moue model of arterial inflammation we found that P-selectin is responsible for a significant part of the platelet-leukocyte interactions. In conclusion, this thesis presents experimental and clinical knowledge to better understand aspects of existent antiplatelet treatments and the studies also provide inputs to the development of future treatment modalities.
13.	Braun, Oscar, et al. (författare) Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease 2008 Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 100:4, s. 626-633 Tidskriftsartikel (refereegranskat)abstract Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 muM ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MFI, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment.
14.	Braun, Oscar, et al. (författare) Increased platelet purinergic sensitivity in peripheral arterial disease--a pilot study. 2005 Ingår i: Platelets. - : Informa UK Limited. - 1369-1635 .- 0953-7104. ; 16:5, s. 261-267 Tidskriftsartikel (refereegranskat)
15.	Braun, Oscar, et al. (författare) Primary and secondary capture of platelets onto inflamed femoral artery endothelium is dependent on P-selectin and PSGL-1. 2008 Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 592, s. 128-132 Tidskriftsartikel (refereegranskat)abstract Platelets constitute a key role in vascular injuries, however, the detailed mechanisms behind platelet-endothelial cell and platelet-leukocyte interactions in the femoral artery are not yet fully elucidated. We used intravital fluorescence microscopy of the femoral artery in C57BL/6 mice to study primary and secondary capture of platelets onto endothelial cells as well as onto adherent platelets and leukocytes in vivo. By use of monoclonal antibodies, the role of P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) in these adhesive interactions in mice exposed to endotoxin was determined. Intravenous injection of endotoxin significantly increased gene expression of P-selectin as well as platelet tethering, rolling and adhesion in the femoral artery. Pretreatment with the anti-PSGL-1 antibody decreased platelet tethering by 85%, platelet rolling by 88% and platelet adhesion by 96%. Immunoneutralization of P-selectin reduced platelet tethering by 91%, platelet rolling by 98%, and platelet adhesion by 97%. In addition, inhibition of P-selectin and PSGL-1 completely abolished secondary capture of platelets onto adherent platelets and leukocytes. Our data show that P-selectin and PSGL-1 mediate early interactions between platelets and other cells, including endothelial cells and leukocytes, in inflamed arteries. These novel results suggest that interference with P-selectin and PSGL-1 may be a useful target in strategies aiming to protect the vascular wall during arterial inflammation.
16.	Braun, Oscar, et al. (författare) Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y(1) and the P2Y (12) receptor and is correlated with protein expression of P2Y (12). 2007 Ingår i: Purinergic Signalling. - : Springer Science and Business Media LLC. - 1573-9546 .- 1573-9538. ; 3:3, s. 195-201 Tidskriftsartikel (refereegranskat)abstract Two ADP receptors have been identified on human platelets: P2Y(1) and P2Y(12). The P2Y(12) receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y(1) blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y(12) and P2Y(1) receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y(1) and P2Y(12) receptor expression on both RNA and protein level were determined, as well as the P2Y(12) H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y(12) receptor and partly due to activation of the P2Y(1) receptor, which is unaffected by clopidogrel. Moreover, a correlation between increased P2Y(12) protein expression on platelets and decreased response to clopidogrel was noticed, r(2)=0.43 (P<0.05). No correlation was found between P2Y(12) mRNA levels and clopidogrel resistance, indicating post-transcriptional mechanisms. To achieve additional ADP inhibition in platelets, antagonists directed at the P2Y(1) receptor could be more promising than the development of more potent P2Y(12) receptor antagonists.
17.	Braun, Oscar Ö., et al. (författare) Continuous-flow LVADs in the Nordic countries : complications and mortality and its predictors 2019 Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 53:1, s. 14-20 Tidskriftsartikel (refereegranskat)abstract Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries.Design: This was a retrospective, international, multicenter cohort study.Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p < .001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively.Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.
18.	Bui, Quan M., et al. (författare) The value of Stanford integrated psychosocial assessment for transplantation (SIPAT) in prediction of clinical outcomes following left ventricular assist device (LVAD) implantation 2019 Ingår i: Heart and Lung. - : Elsevier BV. - 0147-9563. ; 48:2, s. 85-89 Tidskriftsartikel (refereegranskat)abstract Background: The Stanford integrated psychosocial assessment for transplantation (SIPAT) is a validated psychosocial evaluation tool in the transplant population. Objective: We evaluated SIPAT in predicting post-left ventricular assist device (LVAD) outcomes, including cumulative re-admissions, driveline infections, pump malfunction, pump thrombosis, gastrointestinal bleeding, major bleeding, stroke and right ventricular failure. Methods: This retrospective study included 50 LVAD patients at an academic institution in the United States who had a pre-implant SIPAT score during the years 2015-2017. Patients were split into two groups based on SIPAT score, separating a “excellent”/“good” from a “minimally acceptable”/“poor” candidate. Poisson regression, using SIPAT as both a categorical and continuous variable, was used to compare the incidence rates of the primary outcome of cumulative re-admissions and secondary outcomes of LVAD complications. Results: The patient cohort was predominantly male 93.5% vs 89.4% (p = 0.629) with a median age of 67.0 vs 58.0 years (p = 0.037), planned destination therapy 48.4% vs 68.4% (p = 0.242) and median LVAD follow-up time of 241 vs 379 days (p = 0.10) in the low- and high- SIPAT groups, respectively. SIPAT was not a significant predictor for cumulative re-admissions, but there was an association between higher SIPAT scores and major bleeding. Conclusion: In this single-center retrospective study, SIPAT did not predict cumulative re-admissions. Further study is required to validate SIPAT before clinical implementation.
19.	Dahl, Martin, 1984-, et al. (författare) Impacts of land-use change and urban development on carbon sequestration in tropical seagrass meadow sediments 2022 Ingår i: Marine Environmental Research. - : Elsevier BV. - 0141-1136 .- 1879-0291. ; 176 Tidskriftsartikel (refereegranskat)abstract Seagrass meadows store significant carbon stocks at a global scale, but land-use change and other anthropogenic activities can alter the natural process of organic carbon (Corg) accumulation. Here, we assessed the carbon accumulation history of two seagrass meadows in Zanzibar (Tanzania) that have experienced different degrees of disturbance. The meadow at Stone Town has been highly exposed to urban development during the 20th century, while the Mbweni meadow is located in an area with relatively low impacts but historical clearing of adjacent mangroves. The results showed that the two sites had similar sedimentary Corg accumulation rates (22–25 g m−2 yr−1) since the 1940s, while during the last two decades (∼1998 until 2018) they exhibited 24–30% higher accumulation of Corg, which was linked to shifts in Corg sources. The increase in the δ13C isotopic signature of sedimentary Corg (towards a higher seagrass contribution) at the Stone Town site since 1998 points to improved seagrass meadow conditions and Corg accumulation capacity of the meadow after the relocation of a major sewage outlet in the mid–1990s. In contrast, the decrease in the δ13C signatures of sedimentary Corg in the Mbweni meadow since the early 2010s was likely linked to increased Corg run-off of mangrove/terrestrial material following mangrove deforestation. This study exemplifies two different pathways by which land-based human activities can alter the carbon storage capacity of seagrass meadows (i.e. sewage waste management and mangrove deforestation) and showcases opportunities for management of vegetated coastal Corg sinks.
20.	Dahl, Martin, et al. (författare) Impacts of land-use change and urban development on tropical seagrass carbon sinks Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Seagrass meadows store significant carbon stocks at a global scale, but land-use change and anthropogenic activities can alter the natural process of organic carbon (Corg) accumulation. Here, we assessed the carbon accumulation history of two seagrass meadows in Zanzibar (Tanzania) that experienced different degrees of disturbance. The meadow at Stone Town has been highly exposed to urban development during the 20th century, while the Mbweni meadow is located in an area with relatively low impacts but historical clearing of adjacent mangroves. The results showed that the two sites had similar sedimentary Corg accumulation rates (22–25 g m-2 yr-1) since the 1940s, while during the last two decades (~1998 until 2018) they exhibited 24–30% higher accumulation of Corg, which was linked to shifts in Corg sources. The increase in the δ13C isotopic signature of sedimentary Corg (towards a higher seagrass contribution) at the Stone Town site since 1998 points to improved seagrass meadow conditions and Corg accumulation capacity of the meadow after the relocation of a major sewage outlet in the mid–1990s. In contrast, the decrease in the δ13C signatures of sediment Corg in the Mbweni meadow since the early 2010s was likely linked to Corg transport from mangrove/terrestrial material run-off following the mangrove deforestation. This study exemplifies two different pathways by which land-based human activities can alter the carbon storage capacity of seagrass meadows (i.e. sewage waste management and mangrove deforestation) and showcases opportunities for management of vegetated coastal Corg sinks
21.	Darden, Douglas, et al. (författare) Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices : insights from TRAViATA 2021 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 340, s. 26-33 Tidskriftsartikel (refereegranskat)abstract Background: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. Methods: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). Results: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166–701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42–5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. Conclusion: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation.
22.	Erlinge, David, et al. (författare) Mild Hypothermia Increases Adenosine Diphosphate-Stimulated Platelet Aggregation After Clopidogrel Administration in Healthy Volunteers 2009 Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 29:7, s. 86-86 Konferensbidrag (refereegranskat)
23.	Erlinge, David, et al. (författare) Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo 2008 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 52:24, s. 1968-77 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: We evaluated the prevalence and mechanism of poor responsiveness to clopidogrel and prasugrel in coronary artery disease patients with and without diabetes. BACKGROUND: Low platelet inhibition by clopidogrel is associated with ischemic clinical events. A higher 600-mg loading dose (LD) has been advocated to increase responsiveness to clopidogrel. METHODS: In this study, 110 aspirin-treated patients were randomized to double-blind treatment with clopidogrel 600 mg LD/75 mg maintenance dose (MD) for 28 days or prasugrel 60 mg LD/10 mg MD for 28 days. Pharmacodynamic (PD) response was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The PD poor responsiveness was defined with 4 definitions previously associated with worse clinical outcomes. Active metabolites (AM) of clopidogrel and prasugrel were measured. Clopidogrel AM was added ex vivo. RESULTS: The proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo. CONCLUSIONS: Prasugrel treatment results in significantly fewer PD poor responders compared with clopidogrel after a 600-mg clopidogrel LD and during MD. The mechanism of incomplete platelet inhibition in clopidogrel poor-responder groups and in diabetic patients is lower plasma levels of its AM and not differences in platelet P2Y(12) receptor function.
24.	Gasparovic, Hrvoje, et al. (författare) Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation 2022 Ingår i: Heart and Vessels. - : Springer Science and Business Media LLC. - 0910-8327 .- 1615-2573. ; 37:12, s. 1985-1994 Tidskriftsartikel (refereegranskat)abstract Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61–1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.
25.	Gernhofer, Yan K., et al. (författare) Which advanced heart failure therapy strategy is optimal for patients over 60 years old? 2019 Ingår i: The Journal of cardiovascular surgery. - 0021-9509. ; 60:2, s. 251-258 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The optimal advanced heart failure (HF) therapy strategy for patients aged 60 or older with end-stage HF refractory to optimal medical therapy remains uncertain. This study compares outcomes of three advanced HF therapy strategies in this patient population. METHODS: A single-center retrospective study was conducted in 95 patients aged 60-73 years who had undergone isolated heart transplantation (HTx) or continuous flow left ventricular assist device (LVAD) implantation from 2010 to 2017. Patients were stratified into three cohorts by strategy; HTx-only (N.=25), LVAD-to-HTx (N.=29), and LVAD-only (N.=41). Primary end point was 2-year overall survival. Secondary end points included incidence of post-operative adverse events, freedom from first readmission at 1 year, and percentage of days spent in hospital following advanced HF therapy. RESULTS: Two-year survival was 91% in HTx-only patients, 88% in LVAD-to-HTx patients, and 49% in LVAD-only patients (P=0.0008). No significant difference in post-transplant survival was found between patients with or without LVAD-related adverse events preceding transplantation (P=0.42). One-year freedom from first readmission was 38.3% in HTx-only patients, 17.2% in LVAD-to-HTx patients and 7.3% in LVAD-only patients (P=0.0028). Patients in LVAD-to-HTx cohort had higher incidences of gastrointestinal bleeding (38% vs. 3%; P<0.01), major bleeding (28% vs. 3%; P=0.02), and right heart failure (69% vs. 31%; P<0.01) during post-LVAD period compared with post-HTx period. Their percentage of days spent in hospital during post-LVAD period was significantly higher than post-HTx period (7.9% vs. 1.2%; P<0.001). CONCLUSIONS: Our experience with patients over 60 years old undergoing advanced therapy suggests that HTx-only and LVAD-to-HTx strategies had superior medium-term survival than LVAD-only strategy. LVAD-to-HTx strategy is effective in reducing incidence of adverse events and percentage of hospitalized days in this specific patient population.
26.	Gilje, Patrik, et al. (författare) Plasma Levels of Liver-Specific miR-122 is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia. 2012 Ingår i: Shock. - 1540-0514. ; 37, s. 234-238 Tidskriftsartikel (refereegranskat)abstract AIMS:: Tissue-specific circulating microRNAs are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model we investigated the release pattern of cardiacspecific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. METHODS AND RESULTS:: Pigs were anesthetized and cardiogenic shock was induced by inflation of a PCI-balloon in the proximal LAD for 40 minutes followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n=6) or normothermia (38°C, n=6). Circulating microRNAs were extracted from plasma and measured with quantitative real-time PCR. Tissue specificity was assessed by microRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific whereas miR-208b was expressed exclusively in the heart. In the control group ischemic cardiogenic shock induced a 460.000-fold and a 63.000-fold increase in plasma levels of miR-122 (p<0.05) and miR-208b (p<0.05), respectively. Therapeutic hypothermia significantly diminished the increase of miR-122 compared to the normothermic group (p<0.005). In our model, hypothermia was initiated after coronary reperfusion and did neither affect myocardial damage as previously assessed by magnetic resonance imaging nor the plasma level of miR-208b. CONCLUSIONS:: Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.
27.	Gjesdal, Grunde, et al. (författare) Blood lactate is a predictor of short-term mortality in patients with myocardial infarction complicated by heart failure but without cardiogenic shock 2018 Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 18:1, s. 1-8 Tidskriftsartikel (refereegranskat)abstract Background: Mortality in patients with acute myocardial infarction (AMI) has improved substantially with modern therapy including percutaneous coronary interventions (PCI) but remains high in certain subgroups such as patients presenting with overt cardiogenic shock. However, the risk for AMI in patients presenting acutely with signs of heart failure but without cardiogenic shock is less well described. We aimed to identify risk factors for mortality in AMI patients with heart failure without overt cardiogenic shock. Methods: Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we identified patients with operator-registered heart failure (Killip class II-IV), and evaluated predictors of mortality based on clinical factors from review of patient records. Results: A total of 1260 unique patients with acute myocardial infarction underwent PCI in 2014, of which 77 patients (7%) showed signs of heart failure (Killip II-IV) Overall 30-day mortality in patients with Killip class II-IV was 20% (N = 15). In patients classified Killip IV (1%), 30-day mortality was 50% (N = 6). In patients presenting with mild to moderate heart failure (Killlip class II-III), 30-day mortality was 14% (N = 9). In patients with Killip class II-III, lactate ≥2.5 mmol/L was associated with 30-day mortality, whereas systolic blood pressure < 90 mmHg, age, sex and BMI were not. In patients with lactate < 2.5 mmol/L 30-day mortality was 5% (N = 2) whereas mortality was 28% (N = 7) with lactate ≥2.5 mmol/L. This cut-off provided discriminative information on 30-day mortality (area under ROC curve 0.74). Conclusions: In patients with AMI and signs of mild to moderate heart failure, lactate ≥2.5 mmol/L provides additional prognostic information. Interventions to reduce risk may be targeted to these patients.
28.	Gjesdal, Grunde, et al. (författare) Validation of cause of death classification after heart transplantation and cause-specific life expectancy compared to the general population 2022 Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 36:9 Tidskriftsartikel (refereegranskat)abstract Background: Post heart-transplant survival has increased, but information is lacking on specific causes of death and life expectancy. We aimed to assess cause-specific loss of life-years compared to the general population, evaluate classification for cause of death after heart transplantation, and assess validity of cause of death data from the International Society of Heart and Lung Transplant (ISHLT) registry. Methods: In this single center study, we included 239 heart recipients transplanted between 1988 and 2019 in Lund, Sweden (n = 239, 50% of the transplanted population where the cause of death was available). Two cardiologists retrospectively assigned causes of death according to a published classification (CLASS) in the 91 recipients who died during follow-up. Life expectancy was compared to data from the general population. Results: Compared to the average Swedish population, life expectancy for heart transplant recipients was 20 years shorter (IQR 12.9–27.2). The largest number of life-years lost were for deaths due to acute (49 years) and chronic rejection (27 years). Primary graft dysfunction (24 years) accounted for 24% of deaths, followed by malignancy (20 years) and infection (17 years), each accounting for ∼20% of deaths. Use of CLASS revealed moderate inter-rater agreement (56%) and moderate agreement with the ISHLT registry (62%). Conclusions: Survival after heart transplantation was 20 years lower than in the general population. In the young, more life-years were lost due to acute graft rejection, whereas chronic graft rejection and primary graft failure were more important causes of death in older patients. Agreement was moderate between CLASS and the ISHLT registry classifications.
29.	Guidetti, Federica, et al. (författare) Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease : data from Swedish Heart Failure Registry 2023 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:12, s. 2164-2173 Tidskriftsartikel (refereegranskat)abstract Aims: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. Methods and results: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30–44, 45–59 or ≥60 ml/min/1.73 m2, respectively. An eGFR ≥60 ml/min/1.73 m2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98–1.10), all-cause death (HR 1.02, 95% CI 0.97–1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95–1.02) across the eGFR spectrum including also severe CKD. Conclusions: The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum.
30.	Ho, Gordon, et al. (författare) Management of Arrhythmias and Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Devices 2018 Ingår i: JACC: Clinical Electrophysiology. - : Elsevier BV. - 2405-500X. ; 4:7, s. 847-859 Tidskriftsartikel (refereegranskat)abstract For patients with end-stage heart failure, the use of mechanical circulatory support has increased in the last decade due to improved outcomes with durable left ventricular assist devices. The management of these complex patients requires coordinated care by a multidisciplinary team including cardiac electrophysiologists because atrial and ventricular arrhythmias are prevalent in this population. There have been an increasing number of studies that attempt to address issues regarding arrhythmia management in patients with left ventricular assist devices. The purpose of this review is to provide electrophysiologists with an evidence-based approach to manage a broad spectrum of arrhythmia issues in these patients.
31.	Högberg, Carl, et al. (författare) Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment 2009 Ingår i: Thrombosis Journal. - : Springer Science and Business Media LLC. - 1477-9560. ; 7 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Mild hypothermia is currently standard of care for cardiac arrest patients in many hospitals and a common belief is that hypothermia attenuates platelet aggregation. We wanted to examine the effects of clopidogrel on platelet aggregation during hypothermia.METHODS: Platelet reactivity at 37° C and 33° C was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) in blood from healthy volunteers before, and 24 hours after, a 600 mg loading dose of clopidogrel.RESULTS: Collagen, 5-HT, epinephrine, U46619 and ADP-induced platelet aggregation was unaltered or even increased by hypothermia. After clopidogrel, there was a significant increase in platelet aggregation for 5 and 20 muM ADP at 33° C compared to 37° C (46 ± 5 vs. 34 ± 5% and 58 ± 4 vs. 47 ± 4%, p < 0.001, n = 8). Hypothermia also increased ADP-induced aggregation after pretreatment with the P2Y1 antagonist MRS2500. The decreased responsiveness to clopidogrel during hypothermia could be overcome by addition of the reversible P2Y12 antagonist AZD6140. ADP-induced inhibition of VASP-phosphorylation was unaffected by hypothermia both in the presence and absence of clopidogrel. A dose-response curve for ADP-induced platelet aggregation revealed increased potency for ADP during hypothermia with no difference in efficacy.CONCLUSION: Mild hypothermia did not attenuate platelet aggregation, instead it even increased ADP-stimulated platelet aggregation after clopidogrel treatment. Dual platelet inhibition with aspirin and a P2Y12 receptor antagonist is probably needed for patients with acute coronary syndromes treated with mild hypothermia, and it is possible that future ADP blockers could be of benefit.
32.	Ingvarsson, Annika, et al. (författare) Echocardiographic assessment of chamber size and ventricular function during the first year after heart transplantation 2021 Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:4, s. 355-365 Tidskriftsartikel (refereegranskat)abstract AIMS: Detecting changes in ventricular function after orthotopic heart transplantation (OHT) using transthoracic echocardiography (TTE) is important but interpretation of findings is complicated by lack of data on early graft adaptation. We sought to evaluate echocardiographic measures of ventricular size and function the first year following OHT including speckle tracking derived strain. We also aimed to compare echocardiographic findings to hemodynamic parameters obtained by right heart catheterization (RHC).METHODS AND RESULTS: Fifty OHT patients were examined prospectively with TTE and RHC at 1, 6, and 12 months after OHT. Left ventricle (LV) was assessed with fractional shortening, ejection fraction, and systolic tissue velocities. Right ventricular (RV) evaluation included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S´) and fractional area change (FAC). LV global longitudinal and circumferential strain and RV global longitudinal strain (GLS) and RV lateral wall strain (RVfree) were analysed. No relevant changes occurred in LV echocardiographic parameters, whereas all measures of RV function improved significantly during follow up. There was an increase in TAPSE (12.4±3.3 mm to 14.4±4.3 mm, p<0.01), FAC (36±8% to 41±8%, p<0.01), RV GLS (-15.8±3.4% to -17.8±3.6%, p<0.01) and RVfree (-15.5±3.7% to -18.6±3.6%, p<0.001). Between one and twelve months pulmonary pressures decreased, whereas pulmonary vascular resistance did not.CONCLUSION: Stable OHT recipients reached steady state regarding LV function one month after transplantation. In contrast, RV function displayed gradual improvement the first year following OHT, indicating delayed RV-adaptation as compared to the LV. Improved RV function-parameters were independent of invasively measured pulmonary pressures.
33.	Ingvarsson, Annika, et al. (författare) Impact of bridging with left ventricular assist device on right ventricular function following heart transplantation. 2022 Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 9:3, s. 1864-1874 Tidskriftsartikel (refereegranskat)abstract Patients awaiting orthotopic heart transplantation (OHT) can be bridged utilizing a left ventricular assist device (LVAD) that reduces left ventricular filling pressures, decreases pulmonary artery wedge pressure, and maintains adequate cardiac output. This study set out to examine the poorly investigated area of if and how pre-treatment with LVAD impacts right ventricular (RV) function following OHT.We prospectively evaluated 59 (LVAD n=20) consecutive OHT patients. Transthoracic echocardiography (TTE) was performed in conjunction with right heart catheterization (RHC) at 1, 6, and 12months after OHT. RV function TTE-parameters included tricuspid annular plane systolic excursion (TAPSE), systolic tissue velocity (S'), fractional area change, two-dimensional RV global longitudinal strain and longitudinal strain from the RV lateral wall (RVfree). At 1month after OHT, the LVAD group had significantly better longitudinal RV function than the non-LVAD group: TAPSE (15±3mm vs. 12±2mm, P<0.001), RV global longitudinal strain (-19.8±2.1% vs. -14.3±2.8%, P<0.001), and RVfree (-19.8±2.3% vs. -14.1±2.9%, P<0.001). At this time point, pulmonary vascular resistance (PVR) was also lower [1.2±0.4 Wood Units (WU) vs. 1.6±0.6 WU, P<0.05] in the LVAD group compared with the non-LVAD group. At 6 and 12months, no difference was detected in any of the TTE and RHC measured parameters between the two groups. Between 1 and 12months, all parameters of RV function improved significantly in the non-LVAD group but remained unaltered in the LVAD group.Our results indicate that pre-treatment with LVAD decreases PVR and is associated with significantly better RV function early following OHT. During the first year following transplantation, RV function progressively improved in the non-LVAD group such that at 6 and 12months, no difference in RV function was detected between the groups.
34.	Jakus, Nina, et al. (författare) Improved survival of left ventricular assist device carriers in Europe according to implantation eras : results from the PCHF-VAD registry 2022 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:7, s. 1305-1315 Tidskriftsartikel (refereegranskat)abstract Aims: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. Methods and results: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35–0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23–0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43–0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39–0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02–2.75; p = 0.043). Conclusion: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.
35.	Kato, Norihiro, et al. (författare) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation 2015 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293 Tidskriftsartikel (refereegranskat)abstract We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
36.	Lindholm, Daniel, 1982-, et al. (författare) Caffeine and incidence of dyspnea in patients treated with ticagrelor 2018 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 200, s. 141-143 Tidskriftsartikel (refereegranskat)
37.	Lindholm, Daniel, et al. (författare) Design and rationale of TROCADERO: A TRial Of Caffeine to Alleviate DyspnEa Related to ticagrelOr. 2015 Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 170:3, s. 465-470 Tidskriftsartikel (refereegranskat)abstract Ticagrelor treatment has the side effect of increased incidence of dyspnea. Adenosine-induced dyspnea is augmented by ticagrelor and can be alleviated with the adenosine antagonist theophylline. Caffeine is a closely related xanthine derivative.
38.	Merino, Jordi, et al. (författare) Quality of dietary fat and genetic risk of type 2 diabetes : individual participant data meta-analysis 2019 Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 366 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.DESIGN Individual participant data meta-analysis.DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
39.	Muhammad, Asad, et al. (författare) Platelets support pulmonary recruitment of neutrophils in abdominal sepsis 2009 Ingår i: Critical Care Medicine. - 1530-0293. ; 37:4, s. 1389-1396 Tidskriftsartikel (refereegranskat)abstract Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung. Design: Prospective experimental study. Setting. University Hospital Research Unit. Subject. Male C57BL/6 mice. Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction. Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1. Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)
40.	Radhoe, Sumant P., et al. (författare) Sex-related differences in left ventricular assist device utilization and outcomes : results from the PCHF-VAD registry 2023 Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 10:2, s. 1054-1065 Tidskriftsartikel (refereegranskat)abstract Aims: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. Methods and results: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147–823] days for women and 435 [range 190–816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50–1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33–0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. Conclusions: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.
41.	Rahman, Milladur, et al. (författare) Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis. 2014 Ingår i: Platelets. - : Informa UK Limited. - 1369-1635 .- 0953-7104. ; 25:4, s. 257-263 Tidskriftsartikel (refereegranskat)abstract Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor antagonists have been reported to exert anti-inflammatory effects. Herein, we assessed the impact of platelet inhibition with the P2Y12 receptor antagonist ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Animals were treated with ticagrelor (100 mg/kg) or vehicle prior to CLP induction. Edema formation and bronchoalveolar neutrophils as well as lung damage were quantified. Flow cytometry was used to determine expression of platelet-neutrophil aggregates, neutrophil activation and CD40L expression on platelets. CLP-induced pulmonary infiltration of neutrophils at 24 hours was reduced by 50% in ticagrelor-treated animals. Moreover, ticagrelor abolished CLP-provoked lung edema and decreased lung damage score by 41%. Notably, ticagrelor completely inhibited formation of platelet-neutrophil aggregates and markedly reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a potential role for platelet antagonists, such as ticagrelor, in the management of patients with abdominal sepsis.
42.	Rossini, Lorenzo, et al. (författare) Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices 2021 Ingår i: ASAIO Journal. - 1538-943X. ; 67:1, s. 74-83 Tidskriftsartikel (refereegranskat)abstract The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.
43.	Slotta, Jan, et al. (författare) Central Role of Rho Kinase in Lipopolysaccharide-Induced Platelet Capture on Venous Endothelium. 2008 Ingår i: Journal of Investigative Medicine. - 1708-8267. ; 56:4, s. 720-725 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:: Platelet-endothelial cell interactions play a key role in hemostasis and pathological coagulation and are dependent on different surface molecules that are expressed upon activation (eg, mediated by lipopolysaccharide [LPS]). Recently, we have shown that Rho kinase plays a central role in LPS-mediated leukocyte-endothelial cell interactions. We investigated the role of Rho-kinase in inflammatory interactions between platelets and the endothelium in femoral veins in vivo. METHODS:: Mice were injected intravenously with LPS (0.5 mg/kg)/D-galactosamine (900 mg/kg), and Rho kinase was blocked with fasudil 15 minutes before LPS application. Four hours after LPS administration, intravital fluorescence microscopy of the femoral vein was performed, and primary and secondary platelet-endothelial cell interactions were visualized after in vivo platelet staining with rhodamine 6G. RESULTS:: Intravital microscopy showed a significant increase in platelet tethering, rolling, and firm adhesion as well as platelet secondary capture in LPS-treated mice. Rho-kinase inhibition by fasudil significantly reduced platelet tethering, rolling, and firm adhesion. Interestingly, functional blockade of Rho kinase was also able to diminish secondary platelet capture by 79%. CONCLUSIONS:: From our data, we conclude that Rho-kinase signaling plays a central role in the regulation of LPS-induced platelet-endothelial cell interactions in large veins in vivo. Thus, Rho-kinase inhibition might be useful in prevention or treatment of pathological inflammation and endotoxin-mediated hypercoagulation.
44.	Slotta, J E, et al. (författare) Fasudil, a Rho-kinase inhibitor, inhibits leukocyte adhesion in inflamed large blood vessels in vivo. 2006 Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 55:9, s. 364-367 Tidskriftsartikel (refereegranskat)
45.	Smith, Gustav, et al. (författare) Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. 2012 Ingår i: EuroIntervention. - 1969-6213. ; 8:6, s. 672-678 Tidskriftsartikel (refereegranskat)abstract Aims: The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. Methods and results: We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048). Conclusions: TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.
46.	Steding Ehrenborg, Katarina, et al. (författare) Diastolic Filling in Patients After Heart Transplantation Is Impaired Due to an Altered Geometrical Relationship Between the Left Atrium and Ventricle Ingår i: Journal of the American Heart Association. - 2047-9980. Tidskriftsartikel (refereegranskat)abstract BackgroundThe geometrical relationship between atrial and ventricular short‐axis cross‐sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle.Methods and ResultsThis retrospective, cross‐sectional study included 25 HTx patients (median age, 52 [range, 25–70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52–75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56–82] years), and 15 healthy controls (median age, 64 [range, 58–67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short‐axis area minus the largest atrial short‐axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07–0.19]) compared with controls (median, 0.05 [range, 0.03–0.08], P <0.001), whereas left ventricular volume normalized for THV (left ventricular end‐diastolic volume/THV) was similar between HTx and controls (median, 0.19 [range, 0.12–0.24] and median, 0.22 [range, 0.20–0.25], respectively). At end diastole, when atrioventricular area difference reached its largest positive value in controls, 11 HTx patients (44%) had a negative atrioventricular area difference, indicating impaired diastolic filling.ConclusionsDiastolic filling is impaired in HTx patients due to an altered geometrical relationship between the left atrium and ventricle. When performing cardiac transplantation, a surgical technique that creates a smaller left atrium may improve diastolic filling by aiding hydraulic forces.
47.	Sukma Dewi, Ihdina, et al. (författare) Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular Rejection After Heart Transplantation 2017 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 70:23, s. 2946-2947 Tidskriftsartikel (refereegranskat)
48.	van der Pals, Jesper, et al. (författare) Characteristics and outcomes in patients with atrial fibrillation and acute coronary syndrome treated with ticagrelor and novel oral anticoagulants 2021 Ingår i: Thrombosis Update. - : Elsevier BV. - 2666-5727. ; 3 Tidskriftsartikel (refereegranskat)abstract Introduction: Optimal antithrombotic treatment after an acute coronary syndrome (ACS) in patients with atrial fibrillation is unclear. Data on outcomes in patients on concomitant ticagrelor and the novel oral anticoagulants (NOAC) is scarce. This study therefore sought to describe patient characteristics and treatment outcomes in patients with atrial fibrillation and ACS treated with concomitant ticagrelor and NOACs (double antithrombotic therapy, DT). Materials and methods: We retrospectively identified all ACS patients with atrial fibrillation on DT upon discharge from Skåne University Hospital in Lund, Sweden, between 2016 and 2019. Identified patients were compared with age and sex matched controls with ACS alone treated with ticagrelor and aspirin (DAPT). Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for six months. Results: In total, 341 patients on DT were identified and compared with 341 controls on DAPT. Mean HAS-BLED bleeding risk score was higher in patients on DT (2.9 ± 1.0 vs 2.6+/0.9 units, p < 0.001; DT vs DAPT). The incidence of major bleeding was higher in patients on DT (31 (9.1%) vs 10 (2.9%), p = 0.001; DT vs DAPT), while a composite of all thrombotic events was found to be similar between the groups (8 (2.3%) vs 5 (1.5%), p = NS; DT vs DAPT). Conclusions: While thrombotic events occur at a similar rate, the bleeding rate is higher in patients with atrial fibrillation and ACS treated with DT than in patients with ACS alone treated with DAPT. Patients with atrial fibrillation also have a higher basal bleeding risk.
49.	Varenhorst, Christoph, et al. (författare) Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin 2009 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 157:3, s. 562.e1-9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Variability in response to thienopyridines has led to the development of point-of-care devices to assess adenosine diphosphate (ADP)-induced platelet aggregation. These tests need to be evaluated in comparison to reference measurements of P2Y(12) function during different thienopyridine treatments. METHODS: After a run-in on 75 mg aspirin, 110 subjects were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD. Antiplatelet effects were evaluated by VerifyNow P2Y12 (VN-P2Y12) device (Accumetrics, San Diego, CA), vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, and light transmission aggregometry (LTA). Prasugrel's and clopidogrel's active metabolite concentration were also determined. RESULTS: Dose- and time-dependent inhibition of P2Y(12) was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y(12) function. At high levels of P2Y(12) inhibition, platelet function measured by VN-P2Y12 was maximally inhibited and could not reflect further changes seen with VASP or LTA methods. Correlation was also observed between exposure to clopidogrel's active metabolite and VN-P2Y12 during MD and LD, whereas it was observed only with prasugrel MD. CONCLUSION: The VN-P2Y12 correlated strongly with inhibition of P2Y(12) function, as measured with either VASP or LTA. VN-P2Y12 also correlated to exposure to the active metabolite of prasugrel and clopidogrel up to levels associated with assumed saturation of the P2Y(12) receptor.
50.	Varenhorst, Christoph, et al. (författare) Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes. 2014 Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:22, s. 1762-1762 Tidskriftsartikel (refereegranskat)abstract To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.

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