Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular ... Show moreIntroduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after similar to 90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes.Ethics and dissemination The study was approved by the Charite-Universitatsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations.Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx? TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/DRKS00023323. Recruitment started on January 1, 2021. Show less
BackgroundAbnormal cardiac innervation plays an important role in arrhythmogenicity after myocardial infarction (MI). Data regarding reperfusion models and innervation abnormalities in the medium... Show moreBackgroundAbnormal cardiac innervation plays an important role in arrhythmogenicity after myocardial infarction (MI). Data regarding reperfusion models and innervation abnormalities in the medium to long term after MI are sparse. Histologic quantification of the small-sized cardiac nerves is challenging, and transmural analysis has not been performed.ObjectivesThis study sought to assess cardiac innervation patterns in transmural biopsy sections in a porcine reperfusion model of MI (MI-R) using a novel method for nerve quantification.MethodsTransmural biopsy sections from 4 swine (n = 83) at 3 months after MI-R and 3 controls (n = 38) were stained with picrosirius red (fibrosis) and beta-III-tubulin (autonomic nerves). Biopsy sections were classified as infarct core, border zone, or remote zone. Each biopsy section was analyzed with a custom software pipeline, allowing calculation of nerve density and classification into innervation types at the 1 × 1–mm resolution level. Relocation of the classified squares to the original biopsy position enabled transmural quantification and innervation heterogeneity assessment.ResultsCoexisting hyperinnervation, hypoinnervation, and denervation were present in all transmural MI-R biopsy sections. The innervation heterogeneity was greatest in the infarct core (median: 0.14; IQR: 0.12-0.15), followed by the border zone (median: 0.05; IQR: 0.04-0.07; P = 0.02) and remote zone (median: 0.02; IQR: 0.02-0.03; P < 0.0001). Only in the border zone was a positive linear relation between fibrosis and innervation heterogeneity observed (R = 0.79; P < 0.0001).ConclusionsThis novel method allows quantification of nerve density and heterogeneity in large transmural biopsy sections. In the chronic phase after MI-R, alternating innervation patterns were identified within the same biopsy section. Persistent innervation heterogeneity, in particular in the border zone biopsy sections, may contribute to late arrhythmogenicity. Show less
Catapano, A.L.; Caterina, R. de; Jukema, J.W.; Klempfner, R.; Landmesser, U.; Schiele, F.; Sionis, A. 2023
BackgroundLow-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However,... Show moreBackgroundLow-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However, LDL-C management for post-ACS patients remains challenging in clinical practice.HypothesisThe ACS EuroPath III project was designed to optimize LDL-C management in post-ACS patients by promoting guideline implementation and translating existing evidence into effective actions.MethodsThree surveys targeting cardiologists (n = 555), general practitioners (GPs; n = 445), and patients (n = 662) were conducted in Europe, with the aim of capturing information on patient characteristics and treatment during acute phase, discharge and follow-up. GPs’ and patients’ opinions on key treatment aspects were also collected. Based on survey results, international experts and clinicians identified areas of improvement and generated prototype solutions. Participants voted to select the most feasible and replicable proposals for co-development and implementation.ResultsFive key areas of improvement were identified: (1) inappropriate treatment prescribed at discharge; (2) lack of lipid guidance in the discharge letter; (3) inadequate lipid-lowering therapy (LLT) optimization; (4) gaps in guideline knowledge and lack of referral practices for GPs; (5) patients’ concerns about lipid management. Proposed solutions for these focus areas included development of a treatment algorithm for the acute phase, a standardized GP discharge letter, an assessment tool for LLT efficacy at follow-up, an education plan for GPs/patients and a patient engagement discharge kit. The standardized GP discharge letter and treatment algorithm have been selected as the highest priority solutions for development.ConclusionThese initiatives have the potential to improve adherence to guidelines and patient management after ACS. Show less
Background: Factor V Leiden (FVL) and factor II c.*97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear.... Show moreBackground: Factor V Leiden (FVL) and factor II c.*97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. Objectives: This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians.Methods: We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis & GE;50% in at least 1 main coronary ar-tery or branch. Controls were age-and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modi-fication by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed.Results: The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]).Conclusion: FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic car-diovascular risk factors. Show less
Treskes, R.W.; Akker-van Marle, M.E. van den; Winden, L. van; Keulen, N. van; Velde, E.T. van der; Beeres, S.; ... ; Schalij, M.J. 2022
Background: Smartphone compatible wearables have been released on the consumers market, enabling remote monitoring. Remote monitoring is often named as a tool to reduce the cost of care.Objective:... Show moreBackground: Smartphone compatible wearables have been released on the consumers market, enabling remote monitoring. Remote monitoring is often named as a tool to reduce the cost of care.Objective: The primary purpose of this paper is to describe a cost-utility analysis of an eHealth intervention compared to regular follow-up in patients with acute myocardial infarction (AMI).Methods: In this trial, of which clinical results have been published previously, patients with an AMI were randomized in a 1:1 fashion between an eHealth intervention and regular follow-up. The remote monitoring intervention consisted of a blood pressure monitor, weight scale, electrocardiogram device, and step counter. Furthermore, two in-office outpatient clinic visits were replaced by e-visits. The control group received regular care. The differences in mean costs and quality of life per patient between both groups during one-year follow-up were calculated.Results: Mean costs per patient were euro 2417 +/- 2043 (US $2657 +/- 2246) for the intervention and euro 2888 +/- 2961 (US $3175 +/- 3255) for the control group. This yielded a cost reduction of euro 471 (US $518) per patient. This difference was not statistically significant (95% CI - euro 275 to euro 1217; P=.22, US $-302 to $1338). The average quality-adjusted life years in the first year of follow-up was 0.74 for the intervention group and 0.69 for the control (difference -0.05, 95% CI -0.09 to -0.01; P=.01).Conclusions: eHealth in the outpatient clinic setting for patients who suffered from AMI is likely to be cost-effective compared to regular follow-up. Further research should be done to corroborate these findings in other patient populations and different care settings. Show less
Cabezas, J.M.M.; Bingen, B.O.; Amri, I. al; Scherptong, R.W.C. 2022
OBJECTIVES This study sought to evaluate the ability of uni-and bipolar electrograms collected with a multielectrode catheter with smaller electrodes to: 1) delineate scar; and 2) determine local... Show moreOBJECTIVES This study sought to evaluate the ability of uni-and bipolar electrograms collected with a multielectrode catheter with smaller electrodes to: 1) delineate scar; and 2) determine local scar complexity. BACKGROUND Early reperfusion results in variable endocardial scar, often overlaid with surviving viable myocardium. Although bipolar voltage (BV) mapping is considered the pillar of substrate-based ablation, the role of unipolar voltage (UV) mapping has not been sufficiently explored. It has been suggested that bipolar electrograms collected with small electrode catheters can better identify complex scar geometries. METHODS Twelve swine with early reperfusion infarctions were mapped with the 48-electrode OctaRay catheter and a conventional catheter during sinus rhythm. BV electrograms with double components were identified. Transmural (n = 933) biopsy specimens corresponding to mapping points were obtained, histologically assessed, and classified by scar geometry. RESULTS OctaRay UV (UVOcta) and BV (BVOcta) amplitude were associated with the amount of viable myocardium at a given location, with a stronger association for UVOcta (R2 = 0.767 vs 0.473). Cutoff values of 3.7 mV and 1.0 mV could delineate scar (area under the curve: 0.803 and 0.728 for UVOcta and BVOcta, respectively). The morphology of bipolar electrograms collected with the OctaRay catheter more frequently identified areas with 2 layers of surviving myocardium than electrograms collected with the conventional catheter (84% vs 71%). CONCLUSIONS UV mapping can generate a map to delineate the area of interest when using a multielectrode catheter. Within this area of interest, the morphology of bipolar electrograms can identify areas in which a surviving epicardial layer may overlay a poorly coupled, potentially arrhythmogenic, endocardium. (C) 2022 by the American College of Cardiology Foundation. Show less
Bezhaeva, T.; Karper, J.; Quax, P.H.A.; Vries, M.R. de 2022
Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function... Show moreActivation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure. Show less
Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association... Show moreBackground: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 x 10(-4) in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 x 10(-8)). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice. Show less
Despite the increasing success of interventional coronary reperfusion strategies, mortality related to acute myocardial infarction (MI) is still substantial. MI is defined as sudden death of... Show moreDespite the increasing success of interventional coronary reperfusion strategies, mortality related to acute myocardial infarction (MI) is still substantial. MI is defined as sudden death of myocardial tissue caused by an ischemic episode. Ischaemia leads to adverse remodelling in the affected myocardium, inducing metabolic and ionic perturbations at a single cell level, ultimately leading to cell death. The adult mammalian heart has limited regenerative capacity to replace lost cells. Identifying and enhancing physiological cardioprotective processes may be a promising therapy for patients with MI. Studies report an increasing amount of evidence stating the intricacy of the pathophysiology of the infarcted heart. Besides apoptosis, other cellular phenotypes have emerged as key players in the ischemic myocardium, in particular senescence, inflammation, and dedifferentiation. Furthermore, some cardiomyocytes in the infarct border zone uncouple from the surviving myocardium and dedifferentiate, while other cells become senescent in response to injury and start to produce a pro-inflammatory secretome. Enhancing electric coupling between cardiomyocytes in the border zone, eliminating senescent cells with senolytic compounds, and upregulating cardioprotective cellular processes like autophagy, may increase the number of functional cardiomyocytes and therefore enhance cardiac contractility. This review describes the different cellular phenotypes and pathways implicated in injury, remodelling, and regeneration of the myocardium after MI. Moreover, we discuss implications of the complex pathophysiological attributes of the infarcted heart in designing new therapeutic strategies. Show less
Rokeakh, R.; Nesterova, T.; Ushenin, K.; Polyakova, E.; Sonin, D.; Galagudza, M.; ... ; Solovyova, O. 2021
Species-specific computer models of the heart are a novel powerful tool in studies of life-threatening cardiac arrhythmias. Here, we develop such a model aimed at studying infarction injury in a... Show moreSpecies-specific computer models of the heart are a novel powerful tool in studies of life-threatening cardiac arrhythmias. Here, we develop such a model aimed at studying infarction injury in a rat heart, the most common experimental system to investigate the effects of myocardial damage. We updated the Gattoni2016 cellular ionic model by fitting its parameters to experimental data using a population modeling approach. Using four selected cellular models, we studied 2D spiral wave dynamics and found that they include meandering and break-up. Then, using an anatomically realistic ventricular geometry and fiber orientation in the rat heart, we built a model with a post-infarction scar to study the electrophysiological effects of myocardial damage. A post-infarction scar was simulated as an inexcitable obstacle surrounded by a border zone with modified cardiomyocyte properties. For cellular models, we studied the rotation of scroll waves and found that, depending on the model, we can observe different types of dynamics: anchoring, self-termination or stable rotation of the scroll wave. The observed arrhythmia characteristics coincide with those measured in the experiment. The developed model can be used to study arrhythmia in rat hearts with myocardial damage from ischemia reperfusion and to examine the possible arrhythmogenic effects of various experimental interventions. Show less
Phosphorylcholine is a pro-inflammatory epitope exposed on apoptotic cells, and phosphorylcholine monoclonal immunoglobulin (Ig)G antibodies (PC-mAb) have anti-inflammatory properties. In this... Show morePhosphorylcholine is a pro-inflammatory epitope exposed on apoptotic cells, and phosphorylcholine monoclonal immunoglobulin (Ig)G antibodies (PC-mAb) have anti-inflammatory properties. In this study, we hypothesize that PC-mAb treatment reduces adverse cardiac remodelling and infarct size (IS) following unreperfused transmural myocardial infarction (MI). Unreperfused MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery in hypercholesterolaemic APOE*3-Leiden mice. Three weeks following MI, cardiac magnetic resonance (CMR) imaging showed a reduced LV end-diastolic volume (EDV) by 21% and IS by 31% upon PC-mAb treatment as compared to the vehicle control group. In addition, the LV fibrous content was decreased by 27% and LV wall thickness was better preserved by 47% as determined by histological analysis. Two days following MI, CCL2 concentrations, assessed by use of ELISA, were decreased by 81% and circulating monocytes by 64% as assessed by use of FACS analysis. Additionally, local leucocyte infiltration determined by immunohistological analysis showed a 62% decrease after three weeks. In conclusion, the local and systemic inflammatory responses are limited by PC-mAb treatment resulting in restricted adverse cardiac remodelling and IS following unreperfused MI. This indicates that PC-mAb holds promise as a therapeutic agent following MI limiting adverse cardiac remodelling. Show less
Following acute occlusion of a coronary artery causing myocardial ischemia and implementing first-line treatment involving rapid reperfusion, a dynamic and balanced inflammatory response is... Show moreFollowing acute occlusion of a coronary artery causing myocardial ischemia and implementing first-line treatment involving rapid reperfusion, a dynamic and balanced inflammatory response is initiated to repair and remove damaged cells. Paradoxically, restoration of myocardial blood flow exacerbates cell damage as a result of myocardial ischemia-reperfusion (MI-R) injury, which eventually provokes accelerated apoptosis. In the end, the infarct size still corresponds to the subsequent risk of developing heart failure. Therefore, true understanding of the mechanisms regarding MI-R injury, and its contribution to cell damage and cell death, are of the utmost importance in the search for successful therapeutic interventions to finally prevent the onset of heart failure. This review focuses on the role of innate immunity, chemokines, cytokines, and inflammatory cells in all three overlapping phases following experimental, mainly murine, MI-R injury known as the inflammatory, reparative, and maturation phase. It provides a complete state-of-the-art overview including most current research of all post-ischemic processes and phases and additionally summarizes the use of immunomodulatory therapies translated into clinical practice. Show less
Naruse, Y.; Riva, M. de; Watanabe, M.; Wijnmaalen, A.P.; Venlet, J.; Timmer, M.; ... ; Zeppenfeld, K. 2021
Background J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict... Show moreBackground J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict ventricular tachycardia (VT) recurrence after radiofrequency catheter ablation (RFCA) is unknown. Of interest, patients with a wide QRS-complex have been excluded from clinical studies on J-waves, although a J-wave like pattern has been described for wide QRS.Methods We retrospectively included 168 patients (67 +/- 10 years; 146 men) who underwent RFCA of post-infarct VT. J-wave pattern were defined as J-point elevation >= 0.1 mV in at least two leads irrespective of QRS width. fQRS was defined as various RSR` pattern in patients with narrow QRS and more than two R wave in those with wide QRS. The primary endpoint was VT recurrence after RFCA up to 24 months.Results J-wave pattern and fQRS were present in 27 and 28 patients, respectively. Overlap of J-wave pattern and fQRS was observed in nine. During a median follow-up of 20 (interquartile range 9-24) months, 46 (27%) patients had VT recurrence. Kaplan-Meier curves revealed that both J-wave pattern and fQRS were associated with VT recurrence. Multivariate Cox regression analysis demonstrated that the presence of J-wave pattern (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.45-5.58; P = .002) and greater number of induced VT (HR 1.29; 95% CI 1.15-1.45; P < .001) were the independent predictors of VT recurrence.Conclusions A J-wave pattern-but not fQRS-is independently associated with an increased risk of post-infarct VT recurrence after RFCA irrespective of QRS width. This simple non-invasive parameter may identify patients who require additional treatment. Show less
Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a severe vascular disorder caused by mutations in the TGF beta/BMP co-receptor endoglin. Endoglin haploinsufficiency results in vascular... Show moreHereditary hemorrhagic telangiectasia type 1 (HHT1) is a severe vascular disorder caused by mutations in the TGF beta/BMP co-receptor endoglin. Endoglin haploinsufficiency results in vascular malformations and impaired neoangiogenesis. Furthermore, HHT1 patients display an impaired immune response. To date it is not fully understood how endoglin haploinsufficient immune cells contribute to HHT1 pathology. Therefore, we investigated the immune response during tissue repair in Eng+/- mice, a model for HHT1. Eng+/- mice exhibited prolonged infiltration of macrophages after experimentally induced myocardial infarction. Moreover, there was an increased number of inflammatory M1-like macrophages (Ly6C(high)/CD206(-)) at the expense of reparative M2-like macrophages (Ly6C(low)/CD206(+)). Interestingly, HHT1 patients also showed an increased number of inflammatory macrophages. In vitro analysis revealed that TGF beta-induced differentiation of Eng+/- monocytes into M2-like macrophages was blunted. Inhibiting BMP signaling by treating monocytes with LDN-193189 normalized their differentiation. Finally, LDN treatment improved heart function after MI and enhanced vascularization in both wild type and Eng+/- mice. The beneficial effect of LDN was also observed in the hind limb ischemia model. While blood flow recovery was hampered in vehicle-treated animals, LDN treatment improved tissue perfusion recovery in Eng+/- mice. In conclusion, BMPR kinase inhibition restored HHT1 macrophage imbalance in vitro and improved tissue repair after ischemic injury in Eng+/- mice. Show less
Introduction Emergency department (ED) overcrowding is a major healthcare problem associated with worse patient outcomes and increased costs. Attempts to reduce ED overcrowding of patients with... Show moreIntroduction Emergency department (ED) overcrowding is a major healthcare problem associated with worse patient outcomes and increased costs. Attempts to reduce ED overcrowding of patients with cardiac complaints have so far focused on in-hospital triage and rapid risk stratification of patients with chest pain at the ED. The Hollands-Midden Acute Regional Triage-Cardiology (HART-c) study aimed to assess the amount of patients left at home in usual ambulance care as compared with the new prehospital triage method. This method combines paramedic assessment and expert cardiologist consultation using live monitoring, hospital data and real-time admission capacity. Methods and analysis Patients visited by the emergency medical services (EMS) for cardiac complaints are included. EMS consultation consists of medical history, physical examination and vital signs, and ECG measurements. All data are transferred to a newly developed platform for the triage cardiologist. Prehospital data, in-hospital medical records and real-time admission capacity are evaluated. Then a shared decision is made whether admission is necessary and, if so, which hospital is most appropriate. To evaluate safety, all patients left at home and their general practitioners (GPs) are contacted for 30-day adverse events. Ethics and dissemination The study is approved by the LUMC's Medical Ethics Committee. Patients are asked for consent for contacting their GPs. The main results of this trial will be disseminated in one paper. Discussion The HART-c study evaluates the efficacy and feasibility of a prehospital triage method that combines prehospital patient assessment and direct consultation of a cardiologist who has access to live-monitored data, hospital data and real-time hospital admission capacity. We expect this triage method to substantially reduce unnecessary ED visits. Show less
Phosphorylcholine monoclonal immunoglobulin G antibody attenuates the immediate post-ischemic inflammatory response by reducing the proinflammatory chemokine (C-C motif) ligand 2 chemokine and... Show morePhosphorylcholine monoclonal immunoglobulin G antibody attenuates the immediate post-ischemic inflammatory response by reducing the proinflammatory chemokine (C-C motif) ligand 2 chemokine and circulating Ly-6C(hi) monocytes. This subsequently enhances the post-ischemic repair process, resulting in limited adverse cardiac remodeling and preservation of cardiac function. Therefore, phosphorylcholine monoclonal immunoglobulin G antibody therapy may be a valid therapeutic approach against myocardial ischemia-reperfusion injury. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
Abou, R.; Prihadi, E.A.; Goedemans, L.; Geest, R. van der; Mahdiui, M. el; Schalij, M.J.; ... ; Delgado, V. 2020
Aims Left ventricular (LV) mechanical dispersion (MD) may result from heterogeneous electrical conduction and is associated with adverse events. The present study investigated (i) the association... Show moreAims Left ventricular (LV) mechanical dispersion (MD) may result from heterogeneous electrical conduction and is associated with adverse events. The present study investigated (i) the association between LV MD and the extent of LV scar as assessed with contrast-enhanced cardiac magnetic resonance (CMR) and (ii) the prognostic implications of LV MD in patients after ST-segment elevation myocardial infarction.Methods and results LV MD was calculated by echocardiography and myocardial scar was analysed on CMR data retrospectively. Infarct core and border zone were defined as >50% and 35-50% of maximal signal intensity, respectively. Patients were followed for the occurrence of the combined endpoint (all-cause mortality and appropriate implantable cardioverter-defibrillator therapy). In total, 96 patients (87% male, 57 +/- 10 years) were included. Median LV MD was 53.5 ms [interquartile range (IQR) 43.4-62.8]. On CMR, total scar burden was 11.4% (IQR 3.8-17.1%), infarct core tissue 6.2% (IQR 2.0-12.7%), and border zone was 3.5% (IQR 1.5-5.7%). Correlations were observed between LV MD and infarct core (r= 0.517, P < 0.001), total scar burden (r= 0.497, P < 0.001), and border zone (r=0.298, P=0.003). In total, 14 patients (15%) reached the combined endpoint. Patients with LV MD >53.5 ms showed higher event rates as compared to their counterparts. Finally, LV MD showed the highest area under the curve for the prediction of the combined endpoint.Conclusion LV MD is correlated with LV scar burden. In addition, patients with prolonged LV MD showed higher event rates. Finally, LV MD provided the highest predictive value for the combined endpoint when compared with other parameters. Show less
Aims High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to... Show moreAims High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions.Methods and results Within the ICONIC study, a nested case-control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (>= 50%) and non-obstructive (<50%) diameter stenosis, with HRP defined as >= 2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5-525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P < 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26-2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61-3.25, P = 0.42).Conclusions While HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP. Show less