| 1. |
- Snowden, Stuart G., et al.
(författare)
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High-dose simvastatin exhibits enhanced lipid-lowering effects relative to simvastatin/ezetimibe combination therapy
- 2014
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 7:6, s. 955-964
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Tidskriftsartikel (refereegranskat)abstract
- Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q<0.00005), whereas phosphatidylethanolamine (36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease.
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| 2. |
- Yang, Jiangning, et al.
(författare)
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Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
- 2023
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Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:17
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.
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| 3. |
- Akhtar, Zubair, et al.
(författare)
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Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial
- 2023
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:48, s. 7159-7165
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Tidskriftsartikel (refereegranskat)abstract
- Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
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| 4. |
- Andell, Pontus, et al.
(författare)
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Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease : a prespecified subgroup analysis from the DETO2X-AMI trial.
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:8, s. 984-992
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction.METHODS AND RESULTS: =0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions.CONCLUSIONS: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.CLINICAL TRIALS REGISTRATION: NCT02290080.
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| 5. |
- Fransson, Helen, et al.
(författare)
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An automatic method for quantification of myocardium at risk from myocardial perfusion SPECT in patients with acute coronary occlusion.
- 2010
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1532-6551 .- 1071-3581. ; 17, s. 831-840
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In order to determine myocardial salvage, accurate quantification of myocardium at risk (MaR) is necessary. We present a validated novel automatic segmentation algorithm for quantification of MaR by myocardial perfusion SPECT (MPS) in patients with acute coronary occlusion. METHODS AND RESULTS: Twenty-nine patients with coronary occlusion were injected with a perfusion tracer before reperfusion, and underwent rest MPS within 4 hours. The MaR was quantified using the proposed algorithm (Segment software), the software Quantitative Perfusion SPECT (QPS) and by manual segmentation. The Segment MaR algorithm used a threshold of 55% of maximal counts and an a priori model based on normal coronary artery perfusion territories. The MaR was 30 +/- 10% left ventricular mass (%LVM) by manual segmentation, 31 +/- 12%LVM by Segment, and 36 +/- 14%LVM by QPS. There was a good agreement between automatic and manual segmentation for both of the algorithms with a lower bias for Segment (.8 +/- 4.0%LVM) than for QPS (5.8 +/- 5.8%LVM) when compared to manual segmentation. CONCLUSIONS: The Segment MaR algorithm can be used to correctly assess MaR from MPS images in patients with acute coronary occlusion without access to tracer-specific normal database. The MaR in relation to final infarct size enables determination of myocardial salvage.
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| 6. |
- Fröbert, Ole, 1964-, et al.
(författare)
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Clinical Impact of Influenza Vaccination after ST- and Non-ST-segment elevation Myocardial Infarction Insights from the IAMI trial
- 2023
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 255, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI.METHODS: A total of 2571 participants were prospectively enrolled in the IAMI trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2467 participants with ST-segment elevation MI (STEMI, n=1348) or non-ST-segment elevation MI (NSTEMI, n=1119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification.RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P=0.237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at 1 year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P=0.028).CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.
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| 7. |
- Fröbert, Ole, 1964-, et al.
(författare)
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Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 189, s. 94-102
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Tidskriftsartikel (refereegranskat)abstract
- Background: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI.Methods/design: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year.Implications: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.
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| 8. |
- Fröbert, Ole, 1964-, et al.
(författare)
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Influenza Vaccination after Myocardial Infarction : A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial
- 2021
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 144:18, s. 1476-1484
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational and small randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease.Methods: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI) (99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary endpoints: all-cause death, cardiovascular death, MI, and stent thrombosis.Results: Due to the Covid-19 pandemic, the data safety and monitoring board decided to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across eight countries; 1290 assigned to influenza vaccine and 1281 to placebo. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72; 95% confidence interval, 0.52 to 0.99; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59; 0.39 to 0.89; P=0.010), of cardiovascular death 2.7% and 4.5%, (hazard ratio, 0.59; 0.39 to 0.90; P=0.014), and of MI 2.0% and 2.4% (hazard ratio, 0.86; 0.50 to 1.46, P=0.57) in the influenza vaccine and placebo groups, respectively. Conclusions: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, as well as a lower risk of all-cause death and cardiovascular death at 12 months compared with placebo.Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT02831608.
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| 9. |
- Fröbert, Ole, 1964-, et al.
(författare)
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Smokeless tobacco, snus, at admission for percutaneous coronary intervention and future risk for cardiac events
- 2019
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Ingår i: Open Heart. - : BMJ. - 2398-595X .- 2053-3624. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the risk of future death and cardiac events following percutaneous coronary intervention (PCI) in patients using smokeless tobacco, snus, compared with patients not using snus at admission for a first PCI. Methods The Swedish Coronary Angiography and Angioplasty Registry is a prospective registry on coronary diagnostic procedures and interventions. A total of 74 958 patients admitted for a first PCI were enrolled between 2009 and 2018, 6790 snus users and 68 168 not using snus. We used Cox proportional hazards regression for statistical modelling on imputed datasets as well as complete-case datasets. Results Patients using snus were younger (mean (SD) age 61.0 (±10.2) years) than patients not using snus (67.6 (±11.1), p<0.001) and more often male (95.4% vs 67.4%, p<0.001). After multivariable adjustment, snus use was not associated with the primary composite outcome of all-cause mortality, new coronary revascularisation or new hospitalisation for heart failure at 1 year (HR 0.98, 95% CI 0.91 to 1.05). In patients using snus at baseline who underwent a second PCI (n=1443), the duration from the index intervention was shorter for subjects who continued using snus (n=921, 63.8%) compared with subjects who had stopped (mean number of days 285 vs 406, p value=0.001). Conclusions Snus use at admission for a first PCI was not associated with a higher occurrence of all-cause mortality, new revascularisation or heart failure hospitalisation. Discontinuing snus after a first PCI was associated with a significantly longer duration to a subsequent PCI.
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| 10. |
- Henein, Michael Y., et al.
(författare)
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Biomarkers predict in-hospital major adverse cardiac events in covid-19 patients : A multicenter international study
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19.Methods: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE).Results: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan–Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001).Conclusions: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.
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| 11. |
- Henrohn, Dan
(författare)
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Pulmonary Hypertension and the Nitric Oxide System
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary hypertension (PH) is a pathophysiological state associated with several medical conditions, leading to progressive rise in pulmonary vascular resistance (PVR) and right ventricular failure. The clinical PH classification encompasses five main World Health Organization (WHO) groups; pulmonary arterial hypertension (PAH), PH due to left heart disease, PH due to lung diseases and/or hypoxia, chronic thromboembolic PH, and PH with unclear multifactorial mechanisms. Nitric oxide (NO) is a potent vasodilator. Impaired NO production via the classical L-arginine-NO synthase (NOS) pathway has been implicated in PH. Phosphodiesterase-5 (PDE5) inhibitors augment NO signalling, and are considered as one of the cornerstone treatments in PAH. The studies in this thesis aim at to explore and expand the understanding of the NO system in patients with PH.In paper I, we found that PAH patients (WHO group 1) have lower bronchial NO flux compared to healthy controls and patients with PH (WHO group 2–4). This implies reduced bronchial NO formation in PAH. Compared to healthy controls, increased alveolar NO levels were found in patients with PH (WHO group 1-4) and patients with PAH. This may reflect NO diffusion disturbances in the alveoli. PAH patients had higher plasma and salivary levels of nitrite than healthy controls, which may reflect a compensatory upregulation of NOS-independent NO generating pathways.In paper II, we observed that a single oral dose of vardenafil (a PDE5 inhibitor) causes rapid changes in cardiopulmonary haemodynamics in PH patients with PH (WHO group 1-4). We found a correlation between plasma vardenafil concentrations and the changes in mean pulmonary arterial pressure as well as PVR.In paper III, we show that a single oral dose of vardenafil to patients with PH (WHO group 1-4) alter the plasma levels of arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the arginine/ADMA ratio in a favourable manner. The increase in arginine and the arginine/ADMA ratio were associated with improved cardiac index, and the increase in the arginine/ADMA ratio at 540 min correlated with the exposure to vardenafil. Higher baseline plasma levels of ADMA and SDMA and a low arginine/ADMA ratio was associated with a more severe pulmonary haemodynamic disease state in patients with PH.In paper IV, we found that ingestion of beetroot juice, containing inorganic nitrate, increased plasma and salivary levels of nitrate and nitrite, increased exhaled NO, decreased plasma ornithine levels and increased relative arginine availability in patients with PAH compared to placebo. Higher plasma levels of nitrite after the placebo period, reflecting basal conditions, were associated with a more severe PAH phenotype. Our findings indicate that the nitrate-nitrite-NO pathway is active and upregulated in PAH patients.
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| 12. |
- Hofmann, Robin, et al.
(författare)
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Oxygen therapy in suspected acute myocardial infarction
- 2017
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
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| 13. |
- Jernberg, Tomas, et al.
(författare)
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Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction
- 2018
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:24, s. 2754-2762
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure.Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air.Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84–1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0–3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88–1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87–1.33; P=0.52). The results were consistent across all predefined subgroups.Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110.
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| 14. |
- Jung, Christian, et al.
(författare)
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Circulating endothelial and platelet derived microparticles reflect the size of myocardium at risk in patients with ST-elevation myocardial infarction
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 221:1, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Microparticles (MP) are small membrane vesicles, released from activated, damaged and apoptotic endothelial cells (EMP) or platelets (PMP) that may actively modulate inflammation, coagulation and vascular function. We tested the hypothesis that the number of circulating EMP or PMP in acute myocardial infarction correlates with the myocardium at risk (MaR) and infarct size (IS). Methods: EMP were quantified in plasma samples of 36 patients (age: 63 +/- 10 years) with first time ST-elevation myocardial infarction (STEMI) using flow cytometry. EMP were defined as CD31(+)/CD42(-) MP and CD144(+) MP and PMP as CD31(+)/CD42(+) MP. MaR and IS was determined by cardiovascular magnetic resonance imaging one week after the index event. Results: Plasma levels of CD31(+)/CD42(-) EMP were 251.0 +/- 178.8/mu l and CD144(+) 106.3 +/- 33.7/mu l. PMP levels were 579.2 +/- 631.8/mu l. MaR was 31.0 +/- 11.2% of the left ventricle and IS was 11.4 +/- 7.1% of the left ventricle. Patients with STEMI in the left anterior descending artery had higher levels of CD31(+)/CD42(-) EMP and PMP than those with other infarct-related arteries (p<0.05). The numbers of CD31(+)/CD42(-) EMP and PMP correlated to MaR, but not to IS. Conclusions: Circulating EMP and PMP correlate to the size of MaR in patients with STEMI suggesting that they reflect the severity of the endothelial injury and platelet activation during myocardial ischemia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 15. |
- Jung, Christian, et al.
(författare)
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Effects of Myocardial Postconditioning on the Recruitment of Endothelial Progenitor Cells.
- 2012
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Ingår i: Journal of Interventional Cardiology. - : Wiley. - 1540-8183 .- 0896-4327. ; 25:2, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ischemic postconditioning (PostC), brief repetitive cycles of ischemia and reperfusion during early reperfusion, is suggested to protect the myocardium in patients with stent thrombosis-elevation myocardial infarction (STEMI) by improved endothelial dysfunction and alteration of cytokine release. These mechanisms are also of importance for the recruitment of endothelial progenitor cells (EPC), an endogenous repair mechanism for re-endothelialization and neoangiogenesis. The aim of this study was to investigate the effect of PostC on recruitment of EPC. Methods: EPC were analyzed in 20 patients with STEMI randomized to receive four cycles of PostC following percutaneous coronary intervention (PCI) or conventional PCI. Different subpopulations of EPC were quantified immediately and on day 4 using flow cytometry. Myocardium at risk, and infarct size was determined by cardiovascular magnetic resonance. Results: There was no influence of PostC on the number of different EPC (CD34(+) , CD133(+) , CD34(+) CD133(+) , CD34(+) KDR(+) , CD34(-) CD133(+) KDR(+) , CD34(+) CD133(+) KDR(+) ). Left ventricular ejection fraction, myocardium at risk, and infarct size did not correlate to the mobilization of EPC. There was an inverse correlation between the symptom-to-balloon time and the mobilization of progenitor precursor cells (CD34(+) cells: R =-0.527, P = 0.02; CD133(+) cells: R =-0.624, P = 0.004; CD34(+) CD133(+) cells: R =-0.466, P = 0.04). Discussion: Ischemic PostC did not result in improved mobilization of EPC in STEMI patients. The recruitment of progenitor cells seems to be related to the duration of ischemia rather than the size of the ischemic myocardial area. More effort is needed to understand the changes of endothelial surface markers by PostC and their role in EPC recruitment and homing. (J Interven Cardiol 2012;**1-8).
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| 16. |
- Prescott, Eva, et al.
(författare)
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Design and rationale of FLAVOUR : A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction
- 2020
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Patients with coronary artery disease remain at increased risk of recurrent life-threatening cardiovascular events even after adequate guideline-based treatment of conventional risk factors, including blood lipid levels. Inflammation is a critical pathway in the pathogenesis of atherosclerosis and is independently associated with risk of recurrent cardiovascular events. Leukotrienes are potent pro-inflammatory and vasoactive mediators synthesized by leukocytes in atherosclerotic lesions. AZD5718 is a novel antagonist of 5-lipoxygenase activating protein that suppresses leukotriene biosynthesis. FLAVOUR is a phase IIa efficacy and safety study of AZD5718 in patients with myocardial infarction 1–4 weeks before randomization. Stenosis of the left anterior descending coronary artery after percutaneous intervention must be <50%, and Thrombolysis In Myocardial Infarction flow grade must be ≥ 2. Enrolled participants receive standard care plus oral AZD5718 200 mg, 50 mg, or placebo once daily for up to 12 weeks (extended from 4 weeks by protocol amendment). The planned sample size is 100 participants randomized to 12 weeks’ treatment. Change in urine leukotriene E4 levels is the primary efficacy outcome. FLAVOUR also aims to evaluate whether AZD5718 can improve coronary microvascular function, as measured by transthoracic colour Doppler-assisted coronary flow velocity reserve. Centrally pretrained study sonographers use standardized protocols and equipment. Additional outcomes include assessment of comprehensive echocardiographic parameters (including coronary flow, global strain, early diastolic strain rate and left ventricular ejection fraction), arterial stiffness, biomarkers, health-related quality of life, and safety. Specific anti-inflammatory therapies may represent novel promising treatments to reduce residual risk in patients with coronary artery disease. By combining primary pharmacodynamic and secondary cardiovascular surrogate efficacy outcomes, FLAVOUR aims to investigate the mechanistic basis and potential benefits of AZD5718 treatment in patients with coronary artery disease.
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| 17. |
- Prescott, Eva, et al.
(författare)
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Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
- 2022
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 365, s. 34-40
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Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.Patients 7-28days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade≥2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200mg or 50mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.Of 129 randomized patients, 128 received treatment (200mg, n=52; 50mg, n=25; placebo, n=51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200mg, 50mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.gov identifier: NCT03317002.
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| 18. |
- Rafik Hamad, Rangeen, et al.
(författare)
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Assessment of left ventricular structure and function in preeclampsia by echocardiography and cardiovascular biomarkers
- 2009
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:11, s. 2257-2264
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To assess left ventricular (LV) structure and function in preeclampsia, a serious vascular-related pregnancy disorder, by Doppler tissue imaging (DTI) in combination with the levels of cardiovascular biomarkers. MATERIAL AND METHODS: Thirty-five pregnant women with preeclampsia and 30 with normal pregnancy, matched for age and gestational age were examined during pregnancy and 3-6 months after delivery. Transthoracic echocardiography and DTI were performed and blood levels of amino-terminal pro-brain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cystatin C and troponin I were analyzed. RESULTS: There were significant differences in LV and left atrial dimensions and function between the groups. A higher septal and lateral E/E' ratio (E = early transmitral diastolic flow velocity and E' = early diastolic myocardial velocity) (P < 0.0001, 0.0008) and higher levels of NT-pro-BNP, cystatin C, and lower cystatin C estimated GFR in ml/min per 1.73 m (P < 0.0001) were seen in the preeclampsia both during pregnancy and at follow-up. In addition the levels of E/E' ratio lateral and NT-pro-BNP were higher in pregnant women with early-onset preeclampsia necessitating delivery before 34 weeks of gestation than those who developed preeclampsia and delivered at or after 34 weeks (P = 0.0004, 0.005). CONCLUSION: In pregnancies complicated by preeclampsia, especially early-onset preeclampsia, the diastolic LV function is impaired and levels of biomarkers, NT-pro-BNP and cystatin C, are increased in comparison to normal pregnancy.
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| 19. |
- Ritsinger, Viveca, et al.
(författare)
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Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial
- 2023
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 37:10
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes.Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at similar to 20 study sites in Sweden. Patients 18-80 years, without known diabetes and naive to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone.Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries.Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30).
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| 20. |
- Rysz, Susanne, et al.
(författare)
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The effect of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model - A blinded randomized placebo -controlled study in swine
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survival after out-of-hospital cardiac arrest remains poor. Levosimendan could be a new intervention in this setting. Therefore, we conducted a blinded, placebo controlled randomized study investigating the effects of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model in swine. Methods: Twenty-four anesthetised swines underwent experimentally-induced acute myocardial infarction and ventricular fibrillation. At the start of CPR, a bolus dose of levosimendan (12 μg kg-1) or placebo was given followed by a 24-h infusion (0.2 μg kg-1 min-1) after return of spontaneously circulation. Animals were evaluated by risk of death, post-resuscitation hemodynamics and infarction size by magnetic resonance imaging (MRI) up to 32 h post arrest. Results: Spontaneous circulation was restored in all (12/12) animals in the levosimendan group compared to two thirds (8/12) in the placebo group (P = 0.09). Protocol survival was higher for the levosimendan group (P = 0.02) with an estimated 88% lower risk of death compared to placebo (hazard ratio [95% confidence interval] 0.12 [0.01-0.96], P = 0.046). Cardiac output (CO) recovered 40% faster during the first hour of the intensive care period for the levosimendan group (difference 0.13 [0.01-0.26] L min-1P = 0.04). The placebo group required higher inotropic support during the intensive care period which masked an even bigger recovery in CO in the levosimendan group (58%). The MRI showed no difference in myocardial scar size or in myocardial area at risk. Conclusions: Levosimendan given intra-arrest and during the first 24-h of post-resuscitation care improved survival and cardiac performance in this ischemic cardiac arrest model. Institutional Protocol Number; KERIC 5.2.18-14933.
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| 21. |
- Sanchez-Ceinos, Julia, et al.
(författare)
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Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium
- 2024
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Ingår i: CARDIOVASCULAR DIABETOLOGY. - 1475-2840. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium.Methods We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2 -) production by ESR spectroscopy, NF-kappa B binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice.Results Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2 - generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-kappa B p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice.Conclusions EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.
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| 22. |
- Sorensson, Peder, et al.
(författare)
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Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography
- 2010
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Ingår i: Journal of Cardiovascular Magnetic Resonance. - 1097-6647. ; 12, s. 25-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Final infarct size following coronary occlusion is determined by the duration of ischemia, the size of myocardium at risk (MaR) and reperfusion injury. The reference method for determining MaR, single-photon emission computed tomography (SPECT) before reperfusion, is impractical in an acute setting. The aim of the present study was to evaluate whether MaR can be determined from the contrast enhanced myocardium using steady-state free precession (SSFP) cine cardiovascular magnetic resonance (CMR) performed one week after the acute event in ST-elevation myocardial infarction (STEMI) patients with total coronary occlusion. Results: Sixteen patients with STEMI (age 64 +/- 8 years) received intravenous 99 m-Tc immediately before primary percutaneous coronary intervention. SPECT was performed within four hours. MaR was defined as the non-perfused myocardial volume derived with SPECT. CMR was performed 7.8 +/- 1.2 days after the myocardial infarction using a protocol in which the contrast agent was administered before acquisition of short-axis SSFP cines. MaR was evaluated as the contrast enhanced myocardial volume in the cines by two blinded observers. MaR determined from the enhanced region on cine CMR correlated significantly with that derived with SPECT (r(2) = 0.78, p < 0.001). The difference in MaR determined by CMR and SPECT was 0.5 +/- 5.1% (mean +/- SD). The interobserver variability of contrast enhanced cine SSFP measurements was 1.6 +/- 3.7% (mean +/- SD) of the left ventricle wall volume. Conclusions: Contrast enhanced SSFP cine CMR performed one week after acute infarction accurately depicts MaR prior to reperfusion in STEMI patients with total occlusion undergoing primary PCI. This suggests that a single CMR examination might be performed for determination of MaR and infarct size.
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| 23. |
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| 24. |
- Sorensson, Peder, et al.
(författare)
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Long-term impact of postconditioning on infarct size and left ventricular ejection fraction in patients with ST-elevation myocardial infarction
- 2013
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ischemic postconditioning (PostC), reperfusion in brief cycles, is known to induce short-term reduction in infarct size in patients with ST elevation myocardial infarction (STEMI), especially among those with large myocardium at risk (MaR). The aim of the present study was to investigate the long-term effect of PostC on infarct size and left ventricular ejection fraction (LVEF). Methods: Sixty-eight patients with a first STEMI were randomised to primary percutaneous coronary intervention (PCI) (n = 35) or PCI followed by PostC (n = 33). MaR was determined as abnormally contracting segments on left ventricular angiogram. Cardiac magnetic resonance was performed at 3 and 12 months for the determination of infarct size and LVEF. Results: Overall there was no difference in infarct size expressed in percentage of MaR between patients randomised to the control (31%; 23, 41) and PostC (31%; 23, 43) groups at 12 months. Likewise there was no difference in LVEF between control (49%; 41, 55) and PostC (52%; 45, 55). In contrast, patients in the PostC group with MaR in the upper quartile had a significantly smaller infarct size (29%; 18, 38) than those in the control group (40%; 34, 48; p < 0.05) at 12 months. In these patients LVEF was higher in the PostC (47%; 43, 50) compared to the control group (38%; 34, 42; p < 0.01). Conclusions: In this long-term follow-up study PostC did not reduce infarct size in relation to MaR or improved LVEF in the overall study population. However, the present data suggest that PostC exerts long-term beneficial effects in patients with large MaR thereby extending previously published short-term observations.
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| 25. |
- Sundqvist, Michaela L, et al.
(författare)
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A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure.
- 2020
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 111:4, s. 749-756
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function.OBJECTIVE: In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content.DESIGN: We enrolled 243 subjects, 50-70 y old, with a clinic systolic BP (SBP) of 130-159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups.RESULTS: A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups.CONCLUSIONS: A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.
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| 26. |
- Tufvesson, Jane, et al.
(författare)
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Automatic segmentation of myocardium at risk from contrast enhanced SSFP CMR: validation against expert readers and SPECT.
- 2016
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Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Efficacy of reperfusion therapy can be assessed as myocardial salvage index (MSI) by determining the size of myocardium at risk (MaR) and myocardial infarction (MI), (MSI = 1-MI/MaR). Cardiovascular magnetic resonance (CMR) can be used to assess MI by late gadolinium enhancement (LGE) and MaR by either T2-weighted imaging or contrast enhanced SSFP (CE-SSFP). Automatic segmentation algorithms have been developed and validated for MI by LGE as well as for MaR by T2-weighted imaging. There are, however, no algorithms available for CE-SSFP. Therefore, the aim of this study was to develop and validate automatic segmentation of MaR in CE-SSFP.
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| 27. |
- Ubachs, Joey, et al.
(författare)
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Myocardium at risk by magnetic resonance imaging: head-to-head comparison of T2-weighted imaging and contrast-enhanced steady-state free precession.
- 2012
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Ingår i: European Heart Journal-Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404.
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To determine the myocardial salvage index, the extent of infarction needs to be related to the myocardium at risk (MaR). Thus, the ability to assess both infarct size and MaR is of central clinical and scientific importance. The aim of the present study was to explore the relationship between T2-weighted cardiac magnetic resonance (CMR) and contrast-enhanced steady-state free precession (CE-SSFP) CMR for the determination of MaR in patients with acute myocardial infarction. METHODS AND RESULTS: Twenty-one prospectively included patients with first-time ST-elevation myocardial infarction underwent CMR 1 week after primary percutaneous coronary intervention. For the assessment of MaR, T2-weighted images were acquired before and CE-SSFP images were acquired after the injection of a gadolinium-based contrast agent. For the assessment of infarct size, late gadolinium enhancement images were acquired. The MaR by T2-weighted imaging and CE-SSFP was 29 ± 11 and 32 ± 12% of the left ventricle, respectively. Thus, the MaR with T2-weighted imaging was slightly smaller than that by CE-SSFP (-3.0 ± 4.0%; P < 0.01). There was a significant correlation between the two MaR measures (r(2)= 0.89, P < 0.01), independent of the time after contrast agent administration at which the CE-SSFP was commenced (2-8 min). CONCLUSION: There is a good agreement between the MaR assessed by T2-weighted imaging and that assessed by CE-SSFP in patients with reperfused acute myocardial infarction 1 week after the acute event. Thus, both methods can be used to determine MaR and myocardial salvage at this point in time.
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| 28. |
- Wodaje, Tigist, et al.
(författare)
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Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia
- 2024
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 389
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Microvascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). Methods: Four groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. Results: The groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. Conclusions: Coronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.
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