Publications by authors named "David Erlinge"

353 Publications

Terminal T-wave inversion predicts reperfusion tachyarrhythmias in STEMI.

J Electrocardiol 2022 Jan 5;71:28-31. Epub 2022 Jan 5.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Arrhythmia Clinic, Skåne University Hospital, 22185 Lund, Sweden.

Introduction: A reliable electrocardiographic predictor of ventricular fibrillation (VF) in patients with ST elevation myocardial infarction (STEMI) is lacking so far. Previous experimental/simulation study suggested a terminal T-wave inversion (TTWI) in ischemia-related ECG leads corresponding to anterior infarct localization as an independent predictor of reperfusion VF (rVF). This T-wave characteristic has never been tested as a rVF predictor in clinical settings. The aim of this study was to test if terminal T-wave inversion (TTWI) at admission ECG (before reperfusion) can serve as a predictor of ventricular fibrillation during reperfusion (rVF) in patients with anterior STEMI undergoing primary PCI.

Methods And Results: Study population included consecutive patients with anterior infarct localization admitted for primary PCI (n = 181, age 65 [57; 76] years, 66% male). Of those, 14 patients had rVF (rVF group, age 59 [47; 76] years, 64% male) and patients without rVF comprised the No-rVF group (n = 167, age 65 [57; 76] years, 66% male). Association of TTWI with rVF was analyzed using logistic regression analysis adjusted for relevant clinical and electrocardiographic covariates. The prevalence of TTWI in rVF group was 62% comparing to 23% in the No-rVF group, p = 0.005. TTWI was associated with increased risk of rVF (OR 5.51; 95% CI 1.70-17.89; p = 0.004) and remained a significant predictor after adjustment for age, gender, history of MI prior to index admission, VF before reperfusion, T-T, maximal ST elevation, and QRS duration (OR 23.49; 95% CI 3.14-175.91; p = 0.002).

Conclusions: The terminal T-wave inversion in anterior leads before PCI independently predicted rVF in patients with anterior MI thus confirming the previous experimental/simulation findings.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.12.008DOI Listing
January 2022

Development and validation of an artificial neural network algorithm to predict mortality and admission to hospital for heart failure after myocardial infarction: a nationwide population-based study.

Lancet Digit Health 2022 Jan;4(1):e37-e45

Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.

Background: Patients have an estimated mortality of 15-20% within the first year following myocardial infarction and one in four patients who survive myocardial infarction will develop heart failure, severely reducing quality of life and increasing the risk of long-term mortality. We aimed to establish the accuracy of an artificial neural network (ANN) algorithm in predicting 1-year mortality and admission to hospital for heart failure after myocardial infarction.

Methods: In this nationwide population-based study, we used data for all patients admitted to hospital for myocardial infarction and discharged alive from a coronary care unit in Sweden (n=139 288) between Jan 1, 2008, and April 1, 2017, from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) nationwide registry; these patients were randomly divided into training (80%) and testing (20%) datasets. We developed an ANN using 21 variables (including age, sex, medical history, previous medications, in-hospital characteristics, and discharge medications) associated with the outcomes of interest with a back-propagation algorithm in the training dataset and tested it in the testing dataset. The ANN algorithm was then validated in patients with incident myocardial infarction enrolled in the Western Denmark Heart Registry (external validation cohort) between Jan 1, 2008, and Dec 31, 2016. The predictive ability of the model was evaluated using area under the receiver operating characteristic curve (AUROC) and Youden's index was established as a means of identifying an empirical dichotomous cutoff, allowing further evaluation of model performance.

Findings: 139 288 patients who were admitted to hospital for myocardial infarction in the SWEDEHEART registry were randomly divided into a training dataset of 111 558 (80%) patients and a testing dataset of 27 730 (20%) patients. 30 971 patients with myocardial infarction who were enrolled in the Western Denmark Heart Registry were included in the external validation cohort. A first event, either all-cause mortality or admission to hospital for heart failure 1 year after myocardial infarction, occurred in 32 308 (23·2%) patients in the testing and training cohorts only. For 1-year all-cause mortality, the ANN had an AUROC of 0·85 (95% CI 0·84-0·85) in the testing dataset and 0·84 (0·83-0·84) in the external validation cohort. The AUROC for admission to hospital for heart failure within 1 year was 0·82 (0·81-0·82) in the testing dataset and 0·78 (0·77-0·79) in the external validation dataset. With an empirical cutoff the ANN algorithm correctly classified 73·6% of patients with regard to all-cause mortality and 61·5% of patients with regard to admission to hospital for heart failure in the external validation cohort, ruling out adverse outcomes with 97·1-98·7% probability in the external validation cohort.

Interpretation: Identifying patients at a high risk of developing heart failure or death after myocardial infarction could result in tailored therapies and monitoring by the allocation of resources to those at greatest risk.

Funding: The Swedish Heart and Lung Foundation, Swedish Scientific Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, ALF Agreement on Medical Education and Research, Skane University Hospital, The Bundy Academy, the Märta Winkler Foundation, the Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research.
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http://dx.doi.org/10.1016/S2589-7500(21)00228-4DOI Listing
January 2022

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

Circ Cardiovasc Interv 2021 12 14;14(12):e008969. Epub 2021 Dec 14.

Department of Cardiology, Clinical Sciences, Lund University, Sweden (S.K., P.B., M.G., D.E.).

Background: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry).

Methods: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days.

Results: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], =0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], =0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], =0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], =0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], =0.04).

Conclusions: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.008969DOI Listing
December 2021

Dual antithrombotic treatment in chronic coronary syndrome: European Society of Cardiology criteria vs. CHADS-P2A2RC score.

Eur Heart J 2021 Dec 6. Epub 2021 Dec 6.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus 8200, Denmark.

Aims : According to the 2019 European Society of Cardiology (ESC) guidelines on chronic coronary syndromes (CCS), adding a P2Y12 inhibitor or rivaroxaban to aspirin should be considered in high-risk patients. We estimated the proportion of patients eligible for treatment with the ESC criteria and examined if a recently validated risk score (CHADS-P2A2RC) could improve risk prediction.

Methods And Results : We included 61 338 CCS patients undergoing first-time coronary angiography in Western Denmark (2003-16) and classified them according to the ESC criteria and the CHADS-P2A2RC score. The ESC criteria identified 33.9% as high risk, 53.3% as moderate risk, and 12.8% as low risk. The CHADS-P2A2RC score identified 24.9% as high risk (≥4 points), 48.1% as moderate risk (2-3 points), and 27.0% as low risk (≤1 points). Major adverse cardiovascular events per 100 person-years were 4.8 [95% confidence interval (CI) 4.6-5.0] in patients considered high risk with both schemes, 2.1 (95% CI 2.0-2.2) in patients considered high risk with the ESC but low-to-moderate risk with the CHADS-P2A2RC criteria, 3.8 (95% CI 3.6-4.1) in patients considered low-to-moderate risk with the ESC but high risk with the CHADS-P2A2RC criteria, and 1.5 (95% CI 1.5-1.6) in patients considered low-to-moderate risk with both schemes. The CHADS-P2A2RC score enabled correct downward risk reclassification of 5161 patients (8%) without events, yielding an improved specificity of 9.7%, a loss of sensitivity of 4.4%, and an overall net reclassification index of 0.053.

Conclusion : Based on the 2019 ESC guidelines, dual antithrombotic treatment should be considered in one-third of CCS patients. The CHADS-P2A2RC score improved risk classification and may particularly identify low-risk patients with limited benefit from treatment.
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http://dx.doi.org/10.1093/eurheartj/ehab785DOI Listing
December 2021

MVnet: automated time-resolved tracking of the mitral valve plane in CMR long-axis cine images with residual neural networks: a multi-center, multi-vendor study.

J Cardiovasc Magn Reson 2021 12 2;23(1):137. Epub 2021 Dec 2.

Clinical Physiology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.

Background: Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e') are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population.

Methods: The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients.

Results: MVnet achieved a fast segmentation (<1 s/cine) with excellent ICCs of 0.94 (MAPSE) and 0.93 (LV e') and a MV plane tracking error of -0.10 ± 0.97 mm. In a similar manner, the inter-observer variability analysis yielded ICCs of 0.95 and 0.89 and a tracking error of -0.15 ± 1.18 mm, respectively.

Conclusion: A dual-stage deep learning approach for automated annotation of MV points for systolic and diastolic evaluation in CMR long-axis cine images was developed. The method is able to carefully track these points with high accuracy and in a timely manner. This will improve the feasibility of CMR methods which rely on valve tracking and increase their utility in a clinical setting.
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http://dx.doi.org/10.1186/s12968-021-00824-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638514PMC
December 2021

Relation of Early Monomorphic Ventricular Tachycardia to Long-Term Mortality in ST-Elevation Myocardial Infarction.

Am J Cardiol 2022 Jan 10;163:13-19. Epub 2021 Nov 10.

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

Early ventricular tachycardia (VT) and ventricular fibrillation (VF) are associated with increased in-hospital mortality but do not influence the long-term prognosis in ST-elevation myocardial infarction (STEMI). Recent data advocate a differential approach to the type of arrhythmia and indicate long-term mortality hazard associated with monomorphic VT. We aimed to evaluate the prognostic value of early monomorphic VT compared to nonmonomorphic VT/VF in a nonselected cohort of STEMI patients. Consecutive STEMI patients admitted for primary percutaneous coronary intervention from 2007 to 2010 were included. Clinical characteristics were obtained from the Swedish national SWEDEHEART registry. The occurrence and type of early VT/VF were verified in medical records. All-cause mortality 8 years after STEMI was assessed using the Swedish Cause of Death Register. A total of 2,277 STEMI patients were included (age 66 ± 12 years, 70% male), among them 35 (1.5%) with early monomorphic VT and 115 (5.1%) with nonmonomorphic VT/VF. Patients with monomorphic VT had similar clinical characteristics compared to those with nonmonomorphic VT/VF. In total, 22 patients (63%) with monomorphic VT and 43 (37%) with nonmonomorphic VT/VF died by 8 years of follow-up (p = 0.011). Monomorphic VT was associated with a higher risk of all-cause mortality compared to nonmonomorphic VT/VF in univariate analysis (HR 2.03, 95% CI 1.21 to 3.39, p = 0.007) and after adjustment for age and history of myocardial infarction (MI) (HR 1.74, 95% CI 1.02 to 2.97, p = 0.041). Early monomorphic VT in STEMI is associated with a higher risk of all-cause mortality compared to nonmonomorphic VT/VF and deserves further studies to refine risk stratification strategies.
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http://dx.doi.org/10.1016/j.amjcard.2021.09.037DOI Listing
January 2022

Instantaneous wave-free ratio compared with fractional flow reserve in PCI: A cost-minimization analysis.

Int J Cardiol 2021 Dec 30;344:54-59. Epub 2021 Sep 30.

Department of Cardiology, Lund University, Skåne University Hospital, Lund, Sweden. Electronic address:

Background: Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization.

Methods: In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result.

Results: The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions.

Conclusions: IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.054DOI Listing
December 2021

Pretreatment With P2Y12 Inhibitors in Patients With Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Report From the Swedish Coronary Angiography and Angioplasty Registry.

Circ Cardiovasc Interv 2021 11 1;14(11):e010849. Epub 2021 Oct 1.

Department of Cardiology, Karolinska Institutet and Karolinska University Hospital, Solna, Stockholm, Sweden (J.J., C.L., L.M., D.V.).

Background: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population.

Methods: In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding.

Results: We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel.

Conclusions: In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care. Graphic Abstract: A graphic abstract is available for this article.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.121.010849DOI Listing
November 2021

Christmas holiday triggers of myocardial infarction.

Scand Cardiovasc J 2021 Dec 29;55(6):340-344. Epub 2021 Sep 29.

Department of Cardiology, Clinical Sciences, Skane University Hospital, Lund University, Lund, Sweden.

Christmas holidays have been associated with the highest incidence of myocardial infarction (MI). We wanted to assess possible triggers of MI during Christmas. A nationwide, retrospective postal survey with case-control design. All individuals suffering an MI during the Christmas holidays 2018 and 2019 in Sweden were identified through the SWEDEHEART registry and a control group matched in age and gender with chronic coronary syndrome who did not seek medical attention during Christmas were asked for participation. Subjects completed a questionnaire asking them to rate 27 potential MI-triggers as having occurred more or less than usual. A total of 189 patients suffering an MI on Christmas Eve, Christmas Day, or Boxing Day, and 157 patients in the control group responded to the questionnaire, representing response rates of 66% and 62%, respectively. Patients with MI on Christmas experienced more stress (37% vs. 21%,  = .002), depression (21% vs. 11%,  = .024), and worry (26% vs. 10%,  < .001) compared to the control group. The food and sweets consumption was increased in both groups, but to a greater extent in the control group (33% vs. 50%,  = .002 and 32% vs. 43%,  = .031). There were no increases in quarrels, anger, economic worries, or reduced compliance with medication. Patients suffering MI on Christmas holiday experienced higher levels of stress and emotional distress compared to patients with chronic coronary syndrome, possibly contributing to the phenomenon of holiday heart attack. Understanding what factors increase the number of MI on Christmas may help reduce the excess number of MIs and cardiovascular burden.
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http://dx.doi.org/10.1080/14017431.2021.1983638DOI Listing
December 2021

Reply to Trimaille et al.

Am J Physiol Heart Circ Physiol 2021 10;321(4):H750

Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.

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http://dx.doi.org/10.1152/ajpheart.00498.2021DOI Listing
October 2021

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

Circulation 2021 09 20;144(12):916-929. Epub 2021 Sep 20.

Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden.

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.

Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.

Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.

Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448414PMC
September 2021

Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy.

J Am Heart Assoc 2021 09 13;10(18):e022984. Epub 2021 Sep 13.

Department of Cardiology, Clinical Sciences Lund UniversitySkåne University Hospital Lund Sweden.

Background The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; <0.001). Conclusions IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.
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http://dx.doi.org/10.1161/JAHA.121.022984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649533PMC
September 2021

Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction.

Clin Biochem 2021 Dec 5;98:17-23. Epub 2021 Sep 5.

Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.

Background: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment.

Methods: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008-2014. Blood samples were collected day 1-3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events.

Results: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI.

Conclusions: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.09.001DOI Listing
December 2021

Anterior STEMI associated with decreased strain in remote cardiac myocardium.

Int J Cardiovasc Imaging 2021 Sep 5. Epub 2021 Sep 5.

Department of Clinical Sciences Lund, Clinical Physiology, and Skane University Hospital, Lund University, Lund, Sweden.

To assess (1) global longitudinal strain (GLS) by feature tracking cardiac magnetic resonance (CMR) in the sub-acute and chronic phases after ST-elevation infarction (STEMI) and compare to GLS in healthy controls, and (2) the evolution of GLS and regional longitudinal strain (RLS) over time, and their relationship to infarct location and size. Seventy-seven patients from the CHILL-MI-trial (NCT01379261) who underwent CMR 2-6 days and 6 months after STEMI and 27 healthy controls were included for comparison. Steady state free precession (SSFP) long-axis cine images were obtained for GLS and RLS, and late gadolinium enhancement (LGE) images were obtained for infarct size quantifications. GLS was impaired in the sub-acute (- 11.8 ± 3.0%) and chronic phases (- 14.3 ± 2.9%) compared to normal GLS in controls (- 18.4 ± 2.4%; p < 0.001 for both). GLS improved from sub-acute to chronic phase (p < 0.001). GLS was to some extent determined by infarct size (sub-acute: r = 0.2; chronic: r = 0.2, p < 0.001). RLS was impaired in all 6 wall-regions in LAD infarctions in both the sub-acute and chronic phase, while LCx and RCA infarctions had preserved RLS in remote myocardium at both time points. Global longitudinal strain is impaired sub-acutely after STEMI and improvement is seen in the chronic phase, although not reaching normal levels. Global longitudinal strain is only moderately determined by infarct size. Regional longitudinal strain is most impaired in the infarcted region, and LAD infarctions have effects on the whole heart. This could explain why LAD infarcts are more serious than the other culprit vessel infarctions and more often cause heart failure.
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http://dx.doi.org/10.1007/s10554-021-02391-0DOI Listing
September 2021

We need intracoronary physiology guidance before percutaneous coronary intervention, but do we need it post-stenting?

Eur Heart J 2021 12;42(45):4669-4670

Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.

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http://dx.doi.org/10.1093/eurheartj/ehab525DOI Listing
December 2021

Short- and Long-Term Clinical Outcomes for Patients With Takotsubo Syndrome and Patients With Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry.

J Am Heart Assoc 2021 09 1;10(17):e017290. Epub 2021 Sep 1.

Department of Cardiology Sahlgrenska University Hospital Gothenburg Sweden.

Background Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short-term mortality risk of TS, ST-segment-elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS. Methods and Results This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all-cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class ≥2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48-0.76; <0.001), but higher than NSTEMI (adjHR, 2.70; 95% CI, 2.14-3.41; <0.001). Compared with STEMI, TS was associated with a similar risk of acute heart failure (adjHR, 1.26; 95% CI, 0.91-1.76; =0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34-0.89; =0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted interaction STEMI=0.01 and interaction NSTEMI=0.01). Conclusions The 30-day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality.
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http://dx.doi.org/10.1161/JAHA.119.017290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649294PMC
September 2021

Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

Circulation 2021 11 30;144(18):1476-1484. Epub 2021 Aug 30.

Department of Medical Statistics, London School of Hygiene and Tropical Medicine, United Kingdom (T.C., S.J.P.).

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 end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis.

Results: Because of the COVID-19 pandemic, the data safety and monitoring board recommended 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 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. 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% CI, 0.52-0.99]; =0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; =0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; =0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; =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, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.057042DOI Listing
November 2021

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

BMJ Open 2021 08 23;11(8):e049380. Epub 2021 Aug 23.

Department of Cardiology, Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

Introduction: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS.

Methods And Analysis: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022.

Ethics And Dissemination: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible.

Trial Registration Number: NCT04121949; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2021-049380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383880PMC
August 2021

Repolarization and ventricular arrhythmia during targeted temperature management post cardiac arrest.

Resuscitation 2021 09 14;166:74-82. Epub 2021 Jul 14.

Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark.

Background: Targeted temperature management (TTM) following out-of-hospital cardiac arrest (OHCA) prolongs the QT-interval but our knowledge of different temperatures and risk of arrhythmia is incomplete.

Objective: To assess whether the QTc, QT-peak (QTp) and T-peak to T-end interval (TpTe) may be useful markers of ventricular arrhythmia in contemporary post cardiac arrest treatment.

Methods: An ECG-substudy of the TTM-trial (TTM at 33 °C vs. 36 °C) with serial ECGs from 680 (94%) patients. Bazett's (B) and Fridericia's (F) formula were used for heart rate correction of the QT, QTp and TpTe. Ventricular arrhythmia (VT/VF) were registered during the first three days of post cardiac arrest care.

Results: The QT, QTc and QTp intervals were prolonged more at 33 °C compared to 36 °C and restored to similar and lower levels after rewarming. The TpTe-interval remained between 92-100 ms throughout TTM in both groups. The QTc intervals were associated with ventricular arrhythmia, but not after adjustment for cardiac arrest characteristics. The QTp-interval was not associated with risk of ventricular arrhythmia. Heart rate corrected TpTe-intervals were associated with higher risk of arrhythmia (Odds ratio (OR): TpTe(B): 1.12 (1.02-1.23, p = 0.01 TpTe(F): 1.12 (1.02-1.23, p = 0.02) per 20 ms). Further a prolonged TpTe-interval ≥ 90 ms was consistently associated with higher risk (OR: TpTe(B): 2.05 (1.25-3.37), p < 0.01, TpTe(F): 2.14 (1.32-3.49), p < 0.01).

Conclusions: TTM prolongs the QT-interval by prolongation of the QTp-interval without association to increased risk. The TpTe-interval is not significantly affected by core temperature, but heart rate corrected TpTe intervals are robustly associated with risk of ventricular arrhythmia.

Trial Registration: The TTM-trial is registered and accessible at ClinicalTrials.gov (Identifier: NCT01020916).
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http://dx.doi.org/10.1016/j.resuscitation.2021.07.004DOI Listing
September 2021

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

N Engl J Med 2021 06;384(24):2283-2294

From the Department of Clinical Sciences Lund, Sections of Cardiology (J. Dankiewicz, D.E.), Neurology (T. Cronberg, G.L.), and Anesthesiology and Intensive Care (H. Levin, O.B.), Skåne University Hospital Lund, Lund University and Clinical Studies Sweden - Forum South, Skåne University Hospital (S.U.), Lund; the Department of Clinical Sciences Lund, Section of Anesthesia and Intensive Care, Skåne University Hospital Malmö, Malmö, (J. Düring, S.S., H.F.); the Department of Clinical Sciences Lund, Sections of Anesthesiology and Intensive Care (M.A., N.N.) and Clinical Sciences Helsingborg (N.N.), Helsingborg Hospital, Helsingborg; the Department of Clinical Sciences Lund, Section of Anesthesiology and Intensive Care Lund, Hallands Hospital, Halmstad (J.U.); the Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (C.R., A. Lundin); the Department of Clinical Science and Education, Center for Resuscitation Science, Karolinska Institutet, Södersjukhuset, Stockholm (P.N., J. Hollenberg, A.A.); and the Department of Anesthesiology, Intensive Care, and Acute Medicine, Linköping University, Linköping (M.S.C.) - all in Sweden; Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital (J.C.J.), and the Section of Biostatistics, Faculty of Health and Medical Sciences (T.L.), University of Copenhagen, Copenhagen, the Department of Regional Health Research, the Faculty of Health Sciences, University of Southern Denmark, Odense (J.C.J.), the Research Center for Emergency Medicine, the Department of Clinical Medicine (H.K.), and the Department of Intensive Care (A.M.G., S.C.), Aarhus University Hospital, Aarhus - all in Denmark; Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., M.P.G.M., J.M.C.), the Department of Intensive Care, Bristol Royal Infirmary, Bristol (M.T., J. Bewley, K.S.), Essex Cardiothoracic Centre, Basildon (T.R.K., G.V.K.), Anglia Ruskin University School of Medicine, Chelmsford, Essex (T.R.K., G.V.K.), and the Department of Anesthesiology and Intensive Care, Royal Victoria Hospital, Belfast (P.M.) - all in the United Kingdom; Neuroscience Critical Care Research Group and Adult Intensive Care Medicine Service, Centre Hospitalier Universitaire Vaudois-Lausanne University Hospital and University of Lausanne, Lausanne (M. Oddo, S.A.-M.), the Departments of Intensive Care Medicine (M.H.) and Anesthesiology and Pain Medicine, Inselspital (A. Levis), Bern University Hospital, University of Bern, Bern, the Intensive Care Department, Kantonsspital St. Gallen, St. Gallen (C. Schrag, E.F.), the Institute of Intensive Care Medicine, University Hospital Zurich, Zurich (M.M., P.D.W.G.), and the Cardiac Anesthesia and Intensive Care Department, Instituto Cardiocentro Ticino, Lugano (T. Cassina) - all in Switzerland; Descartes University of Paris and Cochin University Hospital, Paris (A.C., P.J.), Medical-Surgical Intensive Care Unit, Dupuytren Teaching Hospital, Limoges (P.V.) - all in France; the 2nd Department of Medicine (J. Bělohlávek, O.S.), and the Department of Anesthesiology and Intensive Care Medicine (M. Otáhal), General University Hospital and First Faculty of Medicine, Charles University, Prague, the 1st Department of Internal Medicine-Cardioangiology, University Hospital Hradec Králové, and Faculty of Medicine, Charles University, Hradec Králové (M. Solar) - all in the Czech Republic; the Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo (J. Hovdenes), the Department of Anesthesiology, Sørlandet Hospital, Arendal (R.B.O.), the Department of Anesthesiology and Intensive Care Medicine, St. Olav's University Hospital, and the Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim (H. Langeland) - all in Norway; the Division of Critical Care and Trauma, George Institute for Global Health, and Bankstown-Lidcombe Hospital, South Western Sydney Local Health District, Sydney (M. Saxena), and the Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine (G.M.E., A.D.N.), and the Department of Intensive Care, Alfred Health (A.D.N.), Monash University, Melbourne - all in Australia; the Medical Research Institute of New Zealand, Intensive Care Unit, Wellington Hospital, Wellington (P.J.Y., L.N.); the Departments of Surgical Sciences and Integrated Diagnostics (P.P.) and Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience (P.P., I.B.), University of Genoa, Genoa, Italy; the Department of Nephrology and Medical Intensive Care (C. Storm), and Klinik und Hochschulambulanz für Neurologie (C.L.), Charité Universitätzmedizin, Berlin, Germany; the Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels (F.S.T.); the Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria (M.J.); the Department of Emergency Medicine, University of Pittsburgh, Pittsburgh (C.C.); and University College Dublin Clinical Research Centre at St. Vincent's University Hospital, Dublin, Ireland (A.D.N.).

Background: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty.

Methods: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device.

Results: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups.

Conclusions: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).
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http://dx.doi.org/10.1056/NEJMoa2100591DOI Listing
June 2021

Predicting outcome in acute myocardial infarction: an analysis investigating 175 circulating biomarkers.

Eur Heart J Acute Cardiovasc Care 2021 Oct;10(7):806-812

Department of Medical Sciences, Uppsala University, Uppsala 751 85, Sweden.

Aims : There is a paucity of studies comprehensively comparing the prognostic value of larger arrays of biomarkers indicative of different pathobiological axes in acute myocardial infarction (MI).

Methods And Results : In this explorative investigation, we simultaneously analysed 175 circulating biomarkers reflecting different inflammatory traits, coagulation activity, endothelial dysfunction, atherogenesis, myocardial dysfunction and damage, apoptosis, kidney function, glucose-, and lipid metabolism. Measurements were performed in samples from 1099 MI patients (SWEDEHEART registry) applying two newer multimarker panels [Proximity Extension Assay (Olink Bioscience), Multiple Reaction Monitoring mass spectrometry]. The prognostic value of biomarkers regarding all-cause mortality, recurrent MI, and heart failure hospitalizations (median follow-up ≤6.6 years) was studied using Lasso analysis, a penalized logistic regression model that considers all biomarkers simultaneously while minimizing the risk for spurious findings. Tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), ovarian cancer-related tumour marker CA 125 (CA-125), and fibroblast growth factor 23 (FGF-23) consistently predicted all-cause mortality in crude and age/sex-adjusted analyses. Growth-differentiation factor 15 (GDF-15) was strongly predictive in the crude model. TRAIL-R2 and B-type natriuretic peptide (BNP) consistently predicted heart failure hospitalizations. No biomarker predicted recurrent MI. The prognostic value of all biomarkers was abrogated following additional adjustment for clinical variables owing to our rigorous statistical approach.

Conclusion : Apart from biomarkers with established prognostic value (i.e. BNP and to some extent GDF-15), several 'novel' biomarkers (i.e. TRAIL-R2, CA-125, FGF-23) emerged as risk predictors in patients with MI. Our data warrant further investigation regarding the utility of these biomarkers for clinical decision-making in acute MI.
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http://dx.doi.org/10.1093/ehjacc/zuaa014DOI Listing
October 2021

A multicentre, prospective, randomised controlled trial to assess the safety and effectiveness of cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction: the COOL AMI EU Pivotal Trial.

EuroIntervention 2021 Aug;17(6):466-473

University Medical Centre Ljubljana, Slovenia.

Background: Despite primary PCI (PPCI), ST-elevation myocardial infarction (STEMI) can still result in large infarct size (IS). New technology with rapid intravascular cooling showed positive signals for reduction in IS in anterior STEMI.

Aims: We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to PPCI in conscious patients, with anterior STEMI, without cardiac arrest.

Methods: Hypothermia was induced using the ZOLL® Proteus™ intravascular cooling system. After randomisation of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischaemic delay in the hypothermia group (232 vs 188 minutes; p<0.001).

Results: There were no differences in angiographic features and PPCI result between the groups. Intravascular temperature at wire crossing was 33.3+0.9°C. Infarct size/left ventricular (IS/LV) mass by cardiac magnetic resonance (CMR) at day 4-6 was 21.3% in the hypothermia group and 20.0% in the control group (p=0.540). Major adverse cardiac events at 30 days increased non-significantly in the hypothermia group (8.6% vs 1.9%; p=0.117) while cardiogenic shock (10.3% vs 0%; p=0.028) and paroxysmal atrial fibrillation (43.1% vs 3.8%; p<0.001) were significantly more frequent in the hypothermia group.

Conclusions: The ZOLL Proteus intravascular cooling system reduced temperature to 33.3°C before PPCI in patients with anterior STEMI. Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in a longer ischaemic delay, did not reduce IS/LV mass and was associated with increased adverse events.
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http://dx.doi.org/10.4244/EIJ-D-21-00348DOI Listing
August 2021

Long-term mortality in patients with ischaemic heart failure revascularized with coronary artery bypass grafting or percutaneous coronary intervention: insights from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

Eur Heart J 2021 07;42(27):2657-2664

Department of Cardiology, Sahlgrenska University Hospital, University of Gothenburg, Bruna straket 16, 413 45 Gothenburg, Sweden.

Aims: To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease.

Methods And Results: We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41-0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17-1.38, Ptrend < 0.001).

Conclusion: In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI.
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http://dx.doi.org/10.1093/eurheartj/ehab273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282315PMC
July 2021

Assessing the external validity of the VALIDATE-SWEDEHEART trial.

Clin Trials 2021 08 20;18(4):427-435. Epub 2021 May 20.

Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.

Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days.

Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up.

Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)).

Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.
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http://dx.doi.org/10.1177/17407745211012438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290983PMC
August 2021

Comparing Effect Estimates in Randomized Trials and Observational Studies From the Same Population: An Application to Percutaneous Coronary Intervention.

J Am Heart Assoc 2021 06 15;10(11):e020357. Epub 2021 May 15.

Unit of Epidemiology Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden.

Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry-the same registry in which the trial was undertaken. The target trial emulation and the VALIDATE trial both estimated little or no effect of bivalirudin versus heparin on the risk of death or myocardial infarction by 180 days (target trial emulation risk ratio for death, 1.21 [95% CI, 0.88 - 1.54]; VALIDATE trial hazard ratio for death, 1.05 [95% CI, 0.78 - 1.41]). The observational data, however, could not capture less severe cases of bleeding, resulting in an inability to define a bleeding outcome like the trial, and could not accurately estimate the comparative risk of death by 14 days, which may be the result of intractable confounding early in follow-up or the inability to precisely emulate the trial's eligibility criteria. Conclusions Using real-world data to emulate a target trial can deliver accurate effect estimates. Yet, even with rich observational data, it is not always possible to estimate the short-term effect of interventions or the effect on outcomes for which data are not routinely collected.
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http://dx.doi.org/10.1161/JAHA.120.020357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483524PMC
June 2021

Effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI): study protocol for a randomized, double-blind, placebo-controlled trial.

Trials 2021 May 10;22(1):338. Epub 2021 May 10.

Department of Cardiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

Background: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI.

Methods: The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months.

Discussion: Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI.

Trial Registration: ClinicalTrials.gov NCT03620266 . Registered on August 8, 2018.
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http://dx.doi.org/10.1186/s13063-021-05287-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112057PMC
May 2021

Methods and results used in the development of a consensus-driven extension to the Consolidated Standards of Reporting Trials (CONSORT) statement for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE).

BMJ Open 2021 04 29;11(4):e049093. Epub 2021 Apr 29.

Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Québec, Canada

Objectives: Randomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.

Methods: The development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.

Results: 27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.

Conclusion: Uptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using cohorts and routinely collected data.
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http://dx.doi.org/10.1136/bmjopen-2021-049093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094349PMC
April 2021

Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study.

Eur J Prev Cardiol 2021 04;28(3):250-259

Department of Clinical Sciences, Danderyd University Hospital, Sweden.

Background: It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis.

Design: The design of this study was as a cross-sectional analysis from a population-based study cohort.

Methods: From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined.

Results: Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)).

Conclusion: Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.
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http://dx.doi.org/10.1177/2047487320909300DOI Listing
April 2021
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