Publications by authors named "Jorrit S Lemkes"

23 Publications

  • Page 1 of 1

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Cardiology, Amphia Hospital, Breda, The Netherlands. Department of Intensive Care Medicine, Amphia Hospital, Breda, The Netherlands. Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands. Department of Intensive Care Medicine, Rijnstate Hospital, Arnhem, The Netherlands. Department of Cardiology, HAGA Hospital, Den Haag, The Netherlands. Department of Intensive Care Medicine, HAGA Hospital, Den Haag, The Netherlands. Department of Cardiology, Maasstad Hospital, Rotterdam, The Netherlands. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maasstad Hospital, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maastricht University Medical Center, University Maastricht, Maastricht, The Netherlands. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Cardiology, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Cardiology, OLVG, Amsterdam, The Netherlands. Department of Intensive Care Medicine, OLVG, Amsterdam, The Netherlands. Department of Cardiology, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Intensive Care Medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. Department of Cardiology, Scheper Hospital, Emmen, The Netherlands. Department of Cardiology, Haaglanden Medical Center, Den Haag, The Netherlands. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands. Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands. Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. Department of Epidemiology and Data Science, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands.

Objectives: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

Design: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

Setting: Nineteen hospitals in The Netherlands.

Patients: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

Interventions: None.

Measurements And Main Results: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

Conclusions: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.
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http://dx.doi.org/10.1097/CCM.0000000000005271DOI Listing
September 2021

Residual Quantitative Flow Ratio to Estimate Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

J Interv Cardiol 2021 31;2021:4339451. Epub 2021 Aug 31.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Objectives: Quantitative flow ratio (QFR) computes fractional flow reserve (FFR) based on invasive coronary angiography (ICA). Residual QFR estimates post-percutaneous coronary intervention (PCI) FFR. This study sought to assess the relationship of residual QFR with post-PCI FFR.

Methods: Residual QFR analysis, using pre-PCI ICA, was attempted in 159 vessels with post-PCI FFR. QFR lesion location was matched with the PCI location to simulate the performed intervention and allow computation of residual QFR. A post-PCI FFR < 0.90 was used to define a suboptimal PCI result.

Results: Residual QFR computation was successful in 128 (81%) vessels. Median residual QFR was higher than post-PCI FFR (0.96 Q1-Q3: 0.91-0.99 vs. 0.91 Q1-Q3: 0.86-0.96, < 0.001). A significant correlation and agreement were observed between residual QFR and post-PCI FFR ( = 0.56 and intraclass correlation coefficient = 0.47, < 0.001 for both). Following PCI, an FFR < 0.90 was observed in 54 (42%) vessels. Specificity, positive predictive value, sensitivity, and negative predictive value of residual QFR for assessment of the PCI result were 96% (95% confidence interval (CI): 87-99%), 89% (95% CI: 72-96%), 44% (95% CI: 31-59%), and 70% (95% CI: 65-75%), respectively. Residual QFR had an accuracy of 74% (95% CI: 66-82%) and an area under the receiver operating characteristic curve of 0.79 (95% CI: 0.71-0.86).

Conclusions: A significant correlation and agreement between residual QFR and post-PCI FFR were observed. Residual QFR ≥ 0.90 did not necessarily commensurate with a satisfactory PCI (post-PCI FFR ≥ 0.90). In contrast, residual QFR exhibited a high specificity for prediction of a suboptimal PCI result.
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http://dx.doi.org/10.1155/2021/4339451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426071PMC
August 2021

Cangrelor Use in Routine Practice: A Two-Center Experience.

J Clin Med 2021 Jun 26;10(13). Epub 2021 Jun 26.

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands.

Cangrelor is the first and only intravenous P2Y-inhibitor and is indicated when (timely) administration of an oral P2Y inhibitor is not feasible in patients undergoing percutaneous coronary intervention (PCI). Our study evaluated the first years of cangrelor use in two Dutch tertiary care centers. Cangrelor-treated patients were identified using a data-mining algorithm. The cumulative incidences of all-cause death, myocardial infarction, definite stent thrombosis and major bleeding at 48 h and 30 days were assessed using Kaplan-Meier estimates. Predictors of 30-day mortality were identified using uni- and multivariable Cox regression models. Between March 2015 and April 2021, 146 patients (median age 63.7 years, 75.3% men) were treated with cangrelor. Cangrelor was primarily used in ST-segment elevation myocardial infarction (STEMI) patients (84.2%). Approximately half required cardiopulmonary resuscitation (54.8%) or mechanical ventilation (48.6%). The cumulative incidence of all-cause death was 11.0% and 25.3% at 48 h and 30 days, respectively. Two cases (1.7%) of definite stent thrombosis, both resulting in myocardial infarction, occurred within 30 days, but after 48 h. No other cases of recurrent myocardial infarction transpired within 30 days. Major bleeding occurred in 5.6% and 12.5% of patients within 48 h and 30 days, respectively. Cardiac arrest at presentation was an independent predictor of 30-day mortality (adjusted hazard ratio 5.20, 95%-CI: 2.10-12.9, < 0.01). Conclusively, cangrelor was used almost exclusively in STEMI patients undergoing PCI. Even though cangrelor was used in high-risk patients, its use was associated with a low rate of stent thrombosis.
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http://dx.doi.org/10.3390/jcm10132829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269409PMC
June 2021

Left ventricular function, strain, and infarct characteristics in patients with transient ST-segment elevation myocardial infarction compared to ST-segment and non-ST-segment elevation myocardial infarctions.

Eur Heart J Cardiovasc Imaging 2021 Jul 1. Epub 2021 Jul 1.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Aims: This study aims to explore cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) function, strain, and infarct size characteristics in patients with transient ST-segment elevation myocardial infarction (TSTEMI) compared to patients with ST-segment and non-ST-segment elevation myocardial infarctions (STEMI and NSTEMI, respectively).

Methods And Results: In total, 407 patients were enrolled in this multicentre observational prospective cohort study. All patients underwent CMR examination 2-8 days after the index event. CMR cine imaging was performed for functional assessment and late gadolinium enhancement to determine infarct size and identify microvascular obstruction (MVO). TSTEMI patients demonstrated the highest LV ejection fraction and the most preserved global LV strain (longitudinal, circumferential, and radial) across the three groups (overall P ≤ 0.001). The CMR-defined infarction was less frequently observed in TSTEMI than in STEMI patients [77 (65%) vs. 124 (98%), P < 0.001] but was comparable with NSTEMI patients [77 (65%) vs. 66 (70%), P = 0.44]. A remarkably smaller infarct size was seen in TSTEMI compared to STEMI patients [1.4 g (0.0-3.9) vs. 13.5 g (5.3-26.8), P < 0.001], whereas infarct size was not significantly different from that in NSTEMI patients [1.4 g (0.0-3.9) vs. 2.1 g (0.0-8.6), P = 0.06]. Whilst the presence of MVO was less frequent in TSTEMI compared to STEMI patients [5 (4%) vs. 53 (31%), P < 0.001], no significant difference was seen compared to NSTEMI patients [5 (4%) vs. 5 (5%), P = 0.72].

Conclusion: TSTEMI yielded favourable cardiac LV function, strain, and infarct-related scar mass compared to STEMI and NSTEMI. LV function and infarct characteristics of TSTEMI tend to be more similar to NSTEMI than STEMI.
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http://dx.doi.org/10.1093/ehjci/jeab114DOI Listing
July 2021

Transient ST-elevation myocardial infarction versus persistent ST-elevation myocardial infarction. An appraisal of patient characteristics and functional outcome.

Int J Cardiol 2021 08 15;336:22-28. Epub 2021 May 15.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, the Netherlands; Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, the Netherlands. Electronic address:

Background: Up to 24% of patients presenting with ST-elevation myocardial infarction (STEMI) show resolution of ST-elevation and symptoms before revascularization. The mechanisms of spontaneous reperfusion are unclear. Given the more favorable outcome of transient STEMI, it is important to obtain further insights in differential aspects.

Methods: We compared 251 patients who presented with transient STEMI (n = 141) or persistent STEMI (n = 110). Clinical angiographic and laboratory data were collected at admission and in subset of patients additional index hemostatic data and at steady-state follow-up. Cardiac magnetic resonance imaging (CMR) was performed at 2-8 days to assess myocardial injury.

Results: Transient STEMI patients had more cardiovascular risk factors than STEMI patients, including more arterial disease and higher cholesterol values. Transient STEMI patients showed angiographically more often no intracoronary thrombus (41.1% vs. 2.7%, P < 0.001) and less often a high thrombus burden (9.2% vs. 40.0%, P < 0.001). CMR revealed microvascular obstruction less frequently (4.2% vs. 34.6%, P < 0.001) and smaller infarct size [1.4%; interquartile range (IQR), 0.0-3.7% vs. 8.8%; IQR, 3.9-17.1% of the left ventricle, P < 0.001] with a better preserved left ventricular ejection fraction (57.8 ± 6.7% vs. 52.5 ± 7.6%, P < 0.001). At steady state, fibrinolysis was higher in transient STEMI, as demonstrated with a reduced clot lysis time (89 ± 20% vs. 99 ± 25%, P = 0.03).

Conclusions: Transient STEMI is a syndrome with less angiographic thrombus burden and spontaneous infarct artery reperfusion, resulting in less myocardial injury than STEMI. The presence of a more effective fibrinolysis in transient STEMI patients may explain these differences and might provide clues for future treatment of STEMI.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.018DOI Listing
August 2021

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

Resuscitation 2021 07 28;164:93-100. Epub 2021 Apr 28.

Department of Intensive care medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands.

Background: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Methods: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32).

Conclusion: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Clinical Trial Registration: Netherlands Trial Register number, NTR4973.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.020DOI Listing
July 2021

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Data Brief 2020 Dec 12;33:106521. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Center, University Maastricht, Maastricht, the Netherlands.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.
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http://dx.doi.org/10.1016/j.dib.2020.106521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691722PMC
December 2020

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy.

Resuscitation 2021 01 12;158:14-22. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Centre, University Maastricht, Maastricht, the Netherlands.

Background: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear.

Objectives: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI).

Methods: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes.

Results: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93).

Conclusion: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival.

Clinical Trial Registration Number: Netherlands trial register (NTR) 4973.
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http://dx.doi.org/10.1016/j.resuscitation.2020.10.026DOI Listing
January 2021

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation: One-Year Outcomes of the COACT Randomized Clinical Trial.

JAMA Cardiol 2020 Dec;5(12):1358-1365

Department of Cardiology, Scheper Hospital, Emmen, the Netherlands.

Importance: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking.

Objective: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy.

Design, Setting, And Participants: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019.

Interventions: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery.

Main Outcomes And Measures: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year.

Results: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64).

Conclusions And Relevance: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes.

Trial Registration: trialregister.nl Identifier: NTR4973.
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http://dx.doi.org/10.1001/jamacardio.2020.3670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489423PMC
December 2020

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial.

J Am Heart Assoc 2020 03 3;9(5):e014411. Epub 2020 Mar 3.

Department of Cardiology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam Cardiovascular Sciences Amsterdam the Netherlands.

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements including calculation of the reactive hyperemia index and clinical follow-up were obtained up to 1.5 years. Major adverse clinical events and bleedings were scored. An intention to treat and a per-protocol analysis were performed. There were no between-group differences in platelet inhibition and endothelial function. At 1 year the reactive hyperemia index in the ticagrelor group was 0.66±0.26 versus 0.61±0.28 in the prasugrel group (=0.31). Platelet inhibition was lower at 1 month versus 1 year in the total study population (61% [42%-81%] versus 83% [61%-95%]; <0.001), and per-protocol platelet inhibition was higher in patients randomized to ticagrelor versus prasugrel at 1 year (91% [83%-97%] versus 82% [65%-92%]; =0.002). There was an improvement in intention to treat endothelial function in patients randomized to ticagrelor (=0.03) but not in patients randomized to prasugrel (=0.88). Major adverse clinical events (10% versus 14%; =0.54) and bleedings (47% versus 63%; =0.10) were similar in the intention-to-treat analysis in both groups. Conclusions Platelet inhibition at 1 year was higher in the ticagrelor group, without an accompanying increase in bleedings. Endothelial function improved over time in ticagrelor patients, while it did not change in the prasugrel group. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02422888.
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http://dx.doi.org/10.1161/JAHA.119.014411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335553PMC
March 2020

1-Year Outcomes of Delayed Versus Immediate Intervention in Patients With Transient ST-Segment Elevation Myocardial Infarction.

JACC Cardiovasc Interv 2019 11 2;12(22):2272-2282. Epub 2019 Sep 2.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Objectives: The aim of the present study was to determine the effect of a delayed versus an immediate invasive approach on final infarct size and clinical outcome up to 1 year.

Background: Up to 24% of patients with acute coronary syndromes present with ST-segment elevation myocardial infarction (STEMI) but show complete resolution of ST-segment elevation and symptoms before revascularization. Current guidelines do not clearly state whether these patients with transient STEMI should be treated with a STEMI-like or non-ST-segment elevation acute coronary syndrome-like intervention strategy.

Methods: In this multicenter trial, 142 patients with transient STEMI were randomized 1:1 to either delayed or immediate coronary intervention. Cardiac magnetic resonance imaging was performed at 4 days and at 4-month follow-up to assess infarct size and myocardial function. Clinical follow-up was performed at 4 and 12 months.

Results: In the delayed (22.7 h) and the immediate (0.4 h) invasive groups, final infarct size as a percentage of the left ventricle was very small (0.4% [interquartile range: 0.0% to 2.5%] vs. 0.4% [interquartile range: 0.0% to 3.5%]; p = 0.79), and left ventricular function was good (mean ejection fraction 59.3 ± 6.5% vs. 59.9 ± 5.4%; p = 0.63). In addition, the overall occurrence of major adverse cardiac events, consisting of death, recurrent infarction, and target lesion revascularization, up to 1 year was low and not different between both groups (5.7% vs. 4.4%, respectively; p = 1.00).

Conclusions: At follow-up, patients with transient STEMI have limited infarction and well-preserved myocardial function in general, and delayed or immediate revascularization has no effect on functional outcome and clinical events up to 1 year.
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http://dx.doi.org/10.1016/j.jcin.2019.07.018DOI Listing
November 2019

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. Reply.

N Engl J Med 2019 07;381(2):189-190

Amsterdam University Medical Center, Amsterdam, the Netherlands

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http://dx.doi.org/10.1056/NEJMc1906523DOI Listing
July 2019

ST-resolution and spontaneous reperfusion in patients with transient ST-segment elevation myocardial infarction.

Eur Heart J 2019 08;40(29):2465

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1093/eurheartj/ehz333DOI Listing
August 2019

Myocardial Blood Flow and Coronary Flow Reserve During 3 Years Following Bioresorbable Vascular Scaffold Versus Metallic Drug-Eluting Stent Implantation: The VANISH Trial.

JACC Cardiovasc Interv 2019 05 24;12(10):967-979. Epub 2019 Apr 24.

Department of Cardiology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands. Electronic address:

Objectives: The randomized clinical VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion: A Randomized [O]HO PET/CT Study) trial was conducted to assess quantitative myocardial blood flow (MBF) during resting, hyperemia, and cold pressor testing (CPT) with positron emission tomographic perfusion imaging after the implantation of a bioresorbable everolimus-eluting scaffold compared with a drug-eluting stent.

Background: Long-term resorption of the bioresorbable everolimus-eluting scaffold reinstates normal vessel geometry, allowing natural regeneration of the newly formed endothelium with revival of vasomotor function.

Methods: Sixty patients (18 to 65 years of age) with single-vessel disease and type A or B1 lesions were randomized in a 1-to-1 fashion. Approximately 1 month, 1 year, and 3 years after device implantation, patients underwent [O]HO cardiac positron emission tomography. The primary endpoint was the interaction of device type and evolution over time of hyperemic MBF, coronary flow reserve, or CPT reserve. At 3-year follow-up, control invasive coronary angiography with optical coherence tomography was performed.

Results: Fifty-nine (98%), 56 (93%), and 51 (85%) patients successfully completed 1-month, 1-year, and 3-year follow-up positron emission tomography, respectively, and no culprit vessel events were registered during follow-up time. The primary study endpoint (i.e., interaction between device type and time) was nonsignificant for hyperemic MBF, CPT reserve, and coronary flow reserve (p > 0.05 for all). In all patients, hyperemic MBF decreased from 1 to 3 years (p = 0.02), while coronary flow reserve was lower at 3-year follow-up compared with 1-month and 1-year follow-up (p = 0.03 for both). After 3 years, percentage area stenosis measured with optical coherence tomography was higher within the bioresorbable everolimus-eluting scaffold compared with the drug-eluting stent (p = 0.03).

Conclusions: The hypothesized beneficial effects of scaffold resorption did not translate to improved MBF during maximal hyperemia or endothelium-dependent vasodilation by CPT.
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http://dx.doi.org/10.1016/j.jcin.2019.03.004DOI Listing
May 2019

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

N Engl J Med 2019 Apr 18;380(15):1397-1407. Epub 2019 Mar 18.

From the Departments of Cardiology (J.S.L., G.N.J., N.W.H., N.R.), Intensive Care Medicine (P.W.G.E., H.M.O.-S.), and Epidemiology and Biostatistics (P.M.V.), Amsterdam University Medical Center VUmc, the Departments of Cardiology (J.P.H.) and Intensive Care Medicine (A.P.J.V.), Amsterdam University Medical Center AMC, and the Departments of Cardiology (M.A.V.) and Intensive Care Medicine (B.B.), Onze Lieve Vrouwe Gasthuis, Amsterdam, the Thorax Center, Erasmus Medical Center (L.S.D.J., E.A.D.), and the Departments of Cardiology (G.J.V.) and Intensive Care Medicine (B.J.W.E.), Maasstad Hospital, Rotterdam, the Departments of Cardiology (M. Meuwissen) and Intensive Care Medicine (T.A.R.), Amphia Hospital, Breda, the Departments of Cardiology (H.A.B.) and Intensive Care Medicine (M.J.B.), Rijnstate Hospital, Arnhem, the Departments of Cardiology (G.B.B.) and Intensive Care Medicine (R.B.), Haga Hospital, and the Department of Cardiology, Haaglanden Medical Center (P.V.O.), The Hague, the Departments of Cardiology (P.H.) and Intensive Care Medicine (I.C.C.H.), University of Groningen, Groningen, the Departments of Cardiology (M.V.) and Intensive Care Medicine (J.J.H.), University Medical Center Utrecht, Utrecht, the Departments of Intensive Care Medicine (A.B.) and Cardiology (M.S.), Medisch Spectrum Twente, Enschede, the Departments of Cardiology (C.C., N.R.) and Intensive Care Medicine (H.H.), Radboud University Medical Center, Nijmegen, the Departments of Cardiology (T.A.C.M.H.) and Intensive Care Medicine (W.R.), Noordwest Ziekenhuisgroep, Alkmaar, the Departments of Intensive Care Medicine (T.S.R.D.) and Cardiology (H.J.G.M.C.), Maastricht University Medical Center, Maastricht, the Department of Cardiology, Scheper Hospital, Emmen (G.A.J.J.), the Department of Cardiology, Isala Hospital, Zwolle (M.T.M.G.), the Department of Cardiology, Tergooi Hospital, Blaricum (K.P.), and the Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg (M. Magro) - all in the Netherlands.

Background: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain.

Methods: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit.

Results: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points.

Conclusions: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).
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http://dx.doi.org/10.1056/NEJMoa1816897DOI Listing
April 2019

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel.

Circulation 2019 01;139(5):636-646

Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands (M.A.H.v.L., N.W.v.d.H., G.N.J., H.E., A.N., J.S.L., G.A.d.W., A.C.v.R., R.N., N.v.R.).

Background: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy.

Methods: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month.

Results: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel.

Conclusions: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035931DOI Listing
January 2019

Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial.

Eur Heart J 2019 01;40(3):283-291

Department of Cardiology, Amsterdam UMC, VU University Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.

Aims: Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR).

Methods And Results: In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography.

Conclusion: Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.
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http://dx.doi.org/10.1093/eurheartj/ehy651DOI Listing
January 2019

Letter by Lemkes et al Regarding Article, "Emergency Coronary Angiography After Out-of-Hospital Cardiac Arrest: Is It Essential or Futile?"

Circ Cardiovasc Interv 2018 08;11(8):e007118

Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands (J.S.L., G.N.J., N.v.R.).

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.118.007118DOI Listing
August 2018

Coronary angiography and percutaneous coronary intervention after out-of-hospital cardiac arrest: major leaps towards improved survival?

J Thorac Dis 2017 Jan;9(1):5-7

Department of Cardiology, Institute of Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.

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http://dx.doi.org/10.21037/jtd.2017.01.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303092PMC
January 2017

Coronary angiography after cardiac arrest: Rationale and design of the COACT trial.

Am Heart J 2016 Oct 14;180:39-45. Epub 2016 Jul 14.

Department of Cardiology, VU University Medical Centre, Amsterdam, the Netherlands.

Background: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated.

Hypothesis: We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI.

Design: In a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment.

Summary: The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival.
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http://dx.doi.org/10.1016/j.ahj.2016.06.025DOI Listing
October 2016

Evaluation of myocardial blood flow and coronary flow reserve after implantation of a bioresorbable vascular scaffold versus metal drug-eluting stent: an interim one-month analysis of the VANISH trial.

EuroIntervention 2016 Aug 5;12(5):e584-94. Epub 2016 Aug 5.

Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.

Aims: A randomised clinical trial of bioresorbable vascular scaffold (BVS) vs. metal drug-eluting stent (DES) was initiated, using positron emission tomography (PET) perfusion imaging to assess the effects of both treatments on (hyperaemic) myocardial blood flow (MBF) and coronary flow reserve (CFR) over a three-year period (VANISH trial). In the present study, early, i.e., after one month, MBF and CFR are reported.

Methods And Results: Sixty patients (45 men [75%], 55±7 years) with a documented single-vessel type A or B1 lesion were included in this single-blind randomised clinical trial. Patients were randomised to implantation of a BVS or DES in a one-to-one fashion. Approximately one month after percutaneous coronary intervention, patients underwent [15O]H2O PET to assess (hyperaemic) MBF, cold pressor test MBF, and CFR. One patient refused PET perfusion at one-month follow-up (in the DES arm). MBF of the treated myocardial territory during rest, CPT, and hyperaemia were not different in BVS-treated patients as compared to DES-treated patients (1.02±0.28 vs. 0.96±0.24 mL·min-1·g-1, p=0.38, 1.20±0.38 vs. 1.08±0.23 mL·min-1·g-1, p=0.16, and 3.04±0.80 vs. 3.33±0.77 mL·min-1·g-1, p=0.16, respectively). CFR of the treated myocardial territory was significantly lower in the BVS-treated patients (3.09±0.94 vs. 3.57±0.85, p<0.05).

Conclusions: No differences in PET-derived absolute myocardial perfusion were observed between BVS-treated patients as compared to DES-treated patients at one-month follow-up. CFR was attenuated in BVS-treated patients, although still within the normal range.
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http://dx.doi.org/10.4244/EIJV12I5A98DOI Listing
August 2016

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

Circ Cardiovasc Interv 2015 Mar;8(3):e001786

From the Departments of Cardiology (P.F.A.T., G.A.d.W., M.R.H., L.F.H.J.R., I.D., P.S.B., R.P.A., R.N., C.P.A., J.S.L., Y.E.A., K.M.M., J.G.F.B., A.C.v.R., A.M.B., P.K., N.v.R.), Epidemiology and Biostatistics (M.W.H.), Radiology and Nuclear Medicine (A.A.L., P.G.R.), and Molecular Cell Biology and Immunology (A.J.G.H.), VU University Medical Center, Amsterdam, The Netherlands; and Cardiovascular Institute, Hospital Clinico San Carlos/Complutense University, Madrid, Spain (M.E.-P., A.Q., C.B., J.E.).

Background: A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET).

Methods And Results: Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04).

Conclusions: Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow.

Clinical Trial Registration Url: http://www.trialregister.nl. Unique identifier: NTR3164.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.114.001786DOI Listing
March 2015

Conscious sedation for EUS of the esophagus and stomach: a double-blind, randomized, controlled trial comparing midazolam with placebo.

Gastrointest Endosc 2003 Jun;57(7):842-7

Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: Patients undergoing EUS usually receive intravenously administered sedative medication. A double-blind, prospective, randomized trial was conducted to compare midazolam with a placebo for EUS of the esophagus and stomach and to assess patient tolerance and endoscopic feasibility.

Methods: A total of 111 patients were randomized to receive midazolam or a placebo. Patients used a visual analogue scale to score pre-EUS anxiety and tolerance for the procedure. Endoscopists used a visual analogue scale to score ease of echoendoscope introduction and overall patient cooperation. Subsequent to EUS, patients were asked if they were willing to undergo the procedure under the same conditions.

Results: The patients' visual analogue scale scores indicated that tolerance for the introduction of the echoendoscope and the procedure overall were both significantly better in the midazolam group. Overall patient tolerance was predicted by sedation (p < 0.001) and pre-EUS anxiety (p = 0.024). Endoscopists' visual analogue scale scores showed that ease of echoendoscope introduction was significantly better in the midazolam group. There was no significant difference in overall patient cooperation during the procedure. There were no significant differences in introduction time, total procedure time, or patients' willingness to undergo the procedure under the same conditions.

Conclusions: EUS of the esophagus and stomach without intravenous sedation is feasible for endoscopists and patients. Patients prefer intravenous administration of midazolam. Assessment of anxiety before EUS may indicate whether administration of midazolam can improve tolerance for the individual patient.
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http://dx.doi.org/10.1016/s0016-5107(03)70018-2DOI Listing
June 2003
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