Publications by authors named "Martijn Meuwissen"

84 Publications

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

Phasic Flow Patterns of Right versus Left Coronary Arteries in Patients Undergoing Clinical Physiological Assessment.

EuroIntervention 2021 Aug 3. Epub 2021 Aug 3.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest this is less pronounced or even reversed in the right coronary artery.

Aims: This study aims to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment.

Methods: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) Study. 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis.

Results: On average, coronary flow was higher in diastole both at rest and during hyperaemia both in the RCA and LCA (mean diastolic-to-systolic velocity ratio was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest , LCAhyp , RCArest and RCAhyp , p<0.001 for between vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom = 1.55 ± 0.35, RCAco-dom =1.40 ± 0.27, RCAnon-dom = 1.35, (SD not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases (97.9%) overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had negligible impact on DSVR in both RCA and LCA (DSVR x hyperaemic stenosis resistance R 2 = 0.018, p=0.03 and DSVR x coronary flow reserve R 2 <0.001, p=0.98).

Conclusions: In patients with CAD undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.
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http://dx.doi.org/10.4244/EIJ-D-21-00189DOI Listing
August 2021

Use of Lithotripsy in a Calcified Saphenous Vein Graft.

JACC Case Rep 2020 Oct 23;2(12):1891-1894. Epub 2020 Sep 23.

Amphia Hospital, Breda, the Netherlands.

Percutaneous coronary interventions in saphenous vein grafts can pose a variety of challenges, such as severely calcified lesions. If these lesions are nondilatable, lithotripsy can arguably be a proper tool for lesion preparation. We present a case in which a nondilatable, calcified saphenous vein graft was successfully treated using Shockwave lithotripsy. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.07.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299138PMC
October 2020

Identification of anatomic risk factors for acute coronary events by optical coherence tomography in patients with myocardial infarction and residual nonflow limiting lesions: rationale and design of the PECTUS-obs study.

BMJ Open 2021 07 7;11(7):e048994. Epub 2021 Jul 7.

Department of Cardiology, Radboudumc, Nijmegen, The Netherlands

Introduction: In patients with myocardial infarction, the decision to treat a nonculprit lesion is generally based on its physiological significance. However, deferral of revascularisation based on nonischaemic fractional flow reserve (FFR) values in these patients results in less favourable outcomes compared with patients with stable coronary artery disease, potentially caused by vulnerable nonculprit lesions. Intravascular optical coherence tomography (OCT) imaging allows for in vivo morphological assessment of plaque 'vulnerability' and might aid in the detection of FFR-negative lesions at high risk for recurrent events.

Methods And Analysis: The PECTUS-obs study is an international multicentre prospective observational study that aims to relate OCT-derived vulnerable plaque characteristics of nonflow limiting, nonculprit lesions to clinical outcome in patients with myocardial infarction. A total of 438 patients presenting with myocardial infarction (ST-elevation myocardial infarction and non-ST-elevation myocardial infarction) will undergo OCT-imaging of any FFR-negative nonculprit lesion for detection of plaque vulnerability. The primary study endpoint is a composite of major adverse cardiovascular events (all-cause mortality, nonfatal myocardial infarction or unplanned revascularisation) at 2-year follow-up. Secondary endpoints will be the same composite at 1-year and 5-year follow-up, target vessel failure, target vessel revascularisation, target lesion failure and target lesion revascularisation.

Ethics And Dissemination: This study has been approved by the Medical Ethics Committee of the region Arnhem-Nijmegen. The results of this study will be disseminated in a main paper and additional papers with subgroup analyses.

Trial Registration Number: NCT03857971.
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http://dx.doi.org/10.1136/bmjopen-2021-048994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264896PMC
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

A case report: adenosine triggered myocardial infarction during myocardial perfusion stress test imaging in a diabetic patient.

Eur Heart J Case Rep 2021 Apr 30;5(4):ytab133. Epub 2021 Apr 30.

Department of Cardiology, Amphia Hospital, Breda, Amphia Ziekenhuis, Molengracht 21, 4818 CK, Breda, The Netherlands.

Background: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) can in general be used safely in daily clinical practice. However, under the right circumstances, it can lead to serious complications.

Case Summary: A 68-year-old female patient with diabetes and a history of inferior ST-elevation myocardial infarction 8 years earlier, visited our outpatient clinic with atypical chest discomfort. In order to assess whether this is due to myocardial ischaemia, MPI-SPECT was ordered. As it was suspected she would not achieve sufficient exercise levels, pharmacologic stress using adenosine was arranged. During the scan, she developed acute myocardial infarction. Subsequent urgent coronary angiography demonstrated a subtotal stenosis in the proximal left anterior descending coronary artery which was successfully stented. She was still free from angina 4 months later.

Discussion: The combination of a reduced systemic and coronary perfusion pressure in the presence of an exhausted coronary autoregulation, may be a starting point for local geometrical changes that initiate the classic cascade of thrombus formation and acute occlusion of coronary arteries during MPI-SPECT. This illustrates the need for continuous patient and electrocardiogram monitoring.
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http://dx.doi.org/10.1093/ehjcr/ytab133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086418PMC
April 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

Time course of coronary flow capacity impairment in ST-segment elevation myocardial infarction.

Eur Heart J Acute Cardiovasc Care 2020 May 26. Epub 2020 May 26.

Amsterdam University Medical Centres - location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, The Netherlands.

Background: Microvascular dysfunction in the setting of ST-elevated myocardial infarction (STEMI) plays an important role in long-term poor clinical outcome. Coronary flow reserve (CFR) is a well-established physiological parameter to interrogate the coronary microcirculation. Together with hyperaemic average peak flow velocity, CFR constitutes the coronary flow capacity (CFC), a validated risk stratification tool in ischaemic heart disease with significant prognostic value. This mechanistic study aims to elucidate the time course of the microcirculation as reflected by alterations in microcirculatory physiological parameters in the acute phase and during follow-up in STEMI patients.

Methods: We assessed CFR and CFC in the culprit and non-culprit vessel in consecutive STEMI patients at baseline (n = 98) and after one-week (n = 64) and six-month follow-up (n = 65).

Results: A significant trend for culprit CFC in infarct size as determined by peak troponin T (p = 0.004), time to reperfusion (p = 0.038), the incidence of final Thrombolysis In Myocardial Infarction 3 flow (p = 0.019) and systolic retrograde flow (p = 0.043) was observed. Non-culprit CFC linear contrast analysis revealed a significant trend in C-reactive protein (p = 0.027), peak troponin T (p < 0.001) and heart rate (p = 0.049). CFC improved both in the culprit and the non-culprit vessel at one-week (both p < 0.001) and six-month follow-up (p = 0.0013 and p < 0.001) compared with baseline.

Conclusion: This study demonstrates the importance of microcirculatory disturbances in the setting of STEMI, which is relevant for the interpretation of intracoronary diagnostic techniques which are influenced by both culprit and non-culprit vascular territories. Assessment of non-culprit vessel CFC in the setting of STEMI might improve risk stratification of these patients following coronary reperfusion of the culprit vessel.
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http://dx.doi.org/10.1177/2048872620918706DOI Listing
May 2020

Interdisciplinary management of acute ischaemic stroke: Current evidence training requirements for endovascular stroke treatment. Position Paper from the ESC Council on Stroke and the European Association for Percutaneous Cardiovascular Interventions with the support of the European Board of Neurointervention.

Eur Heart J 2021 01;42(4):298-307

Cardiocenter, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

This ESC Council on Stroke/EAPCI/EBNI position paper summarizes recommendations for training of cardiologists in endovascular treatment of acute ischaemic stroke. Interventional cardiologists adequately trained to perform endovascular stroke interventions could complement stroke teams to provide the 24/7 on call duty and thus to increase timely access of stroke patients to endovascular treatment. The training requirements for interventional cardiologists to perform endovascular therapy are described in details and should be based on two main principles: (i) patient safety cannot be compromised, (ii) proper training of interventional cardiologists should be under supervision of and guaranteed by a qualified neurointerventionist and within the setting of a stroke team. Interdisciplinary cooperation based on common standards and professional consensus is the key to the quality improvement in stroke treatment.
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http://dx.doi.org/10.1093/eurheartj/ehaa833DOI Listing
January 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

Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL.

J Am Heart Assoc 2020 07 14;9(14):e016130. Epub 2020 Jul 14.

Department of Cardiovascular Medicine Tsuchiura Kyodo General Hospital Tsuchiura Ibaraki Japan.

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect -Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian-Dutch-English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively; <0.001). Compared with the conventional cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR, an ischemic CFC defined as moderately to severely reduced CFC showed higher diagnostic accuracy with higher specificity to predict a >50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR (<0.05). Multivariate analysis revealed lesions with ischemic CFC to be the independent predictor of a significant coronary flow increase after percutaneous coronary intervention (odds ratio, 10.7; 95% CI, 4.6-24.8; <0.001). Conclusions CFC showed significant improvement of identification of lesions that benefit from revascularization compared with CFR with respect to coronary flow increase. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820.
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http://dx.doi.org/10.1161/JAHA.120.016130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660740PMC
July 2020

Objective Identification of Intermediate Lesions Inducing Myocardial Ischemia Using Sequential Intracoronary Pressure and Flow Measurements.

J Am Heart Assoc 2020 07 23;9(13):e015559. Epub 2020 Jun 23.

Department of Interventional Cardiology Amsterdam Cardiovascular Sciences Heart Center Amsterdam UMC-location AMC University of Amsterdam The Netherlands.

Background Although ischemic heart disease has a complex and multilevel origin, the diagnostic approach is mainly focused on focal obstructive disease as assessed by pressure-derived indexes. The prognostic relevance of coronary flow over coronary pressure has been suggested and implies that identification of relevant perfusion abnormalities by invasive physiology techniques is critical for the correct identification of patients who benefit from coronary revascularization. The purpose of this study was to evaluate the diagnostic potential of a sequential approach using pressure-derived indexes instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and coronary flow reserve (CFR) measurements to determine the number of intermediate lesions associated with flow abnormalities after initial pressure measurements. Methods and Results A total of 366 intermediate lesions were assessed with simultaneous intracoronary pressure and flow velocity measurements. Contemporary clinical iFR, FFR, and CFR cut points for myocardial ischemia were applied. A total of 118 (32%) lesions were FFR+ and 136 (37%) lesions were iFR+. Subsequent CFR assessment resulted for FFR in a total of 91 (25%) FFR+/CFR+ and for iFR a total of 111 (30%) iFR+/CFR+ lesions. An iFR, FFR, and invasive flow velocity assessment approach would have yielded 20% of lesions (74 of 366) as ischemic. Conclusions Ultimately, 20% of intermediate lesions are associated with flow abnormalities after applying a pressure and flow velocity sequential approach. If iFR is borderline, FFR has limited additional value, in contrast with CFR. These results emphasize the use of coronary physiology in assessing stenosis severity but may also further question the contemporary reputation of a pressure-based approach as a gold standard for the detection of myocardial ischemia in ischemic heart disease.
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http://dx.doi.org/10.1161/JAHA.119.015559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670511PMC
July 2020

Time course of coronary flow capacity impairment in ST-segment elevation myocardial infarction.

Eur Heart J Acute Cardiovasc Care 2020 May 26:2048872620918706. Epub 2020 May 26.

Amsterdam University Medical Centres - location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, The Netherlands.

Background: Microvascular dysfunction in the setting of ST-elevated myocardial infarction (STEMI) plays an important role in long-term poor clinical outcome. Coronary flow reserve (CFR) is a well-established physiological parameter to interrogate the coronary microcirculation. Together with hyperaemic average peak flow velocity, CFR constitutes the coronary flow capacity (CFC), a validated risk stratification tool in ischaemic heart disease with significant prognostic value. This mechanistic study aims to elucidate the time course of the microcirculation as reflected by alterations in microcirculatory physiological parameters in the acute phase and during follow-up in STEMI patients.

Methods: We assessed CFR and CFC in the culprit and non-culprit vessel in consecutive STEMI patients at baseline ( = 98) and after one-week ( = 64) and six-month follow-up ( = 65).

Results: A significant trend for culprit CFC in infarct size as determined by peak troponin T ( = 0.004), time to reperfusion ( = 0.038), the incidence of final Thrombolysis In Myocardial Infarction 3 flow ( = 0.019) and systolic retrograde flow ( = 0.043) was observed. Non-culprit CFC linear contrast analysis revealed a significant trend in C-reactive protein ( = 0.027), peak troponin T ( < 0.001) and heart rate ( = 0.049). CFC improved both in the culprit and the non-culprit vessel at one-week (both  < 0.001) and six-month follow-up ( = 0.0013 and  < 0.001) compared with baseline.

Conclusion: This study demonstrates the importance of microcirculatory disturbances in the setting of STEMI, which is relevant for the interpretation of intracoronary diagnostic techniques which are influenced by both culprit and non-culprit vascular territories. Assessment of non-culprit vessel CFC in the setting of STEMI might improve risk stratification of these patients following coronary reperfusion of the culprit vessel.
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http://dx.doi.org/10.1177/2048872620918706DOI Listing
May 2020

Coronary Artery Perforation After Shockwave Intravascular Lithotripsy.

JACC Case Rep 2020 Feb 19;2(2):247-249. Epub 2020 Feb 19.

Department of Cardiology, Amphia Ziekenhuis, Breda, the Netherlands.

Severely calcified coronary lesions remain a challenge in current percutaneous coronary interventions. Shockwave intravascular lithotripsy (Shockwave Medical, Inc., Santa Clara, California) is an alternative for rotational atherectomy in such lesions that supports stent deliverability and achieves optimal results. We describe a case of coronary artery perforation after use of this lithotripsy device. ().
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http://dx.doi.org/10.1016/j.jaccas.2019.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298537PMC
February 2020

Impact of clinical and haemodynamic factors on coronary flow reserve and invasive coronary flow capacity in non-obstructed coronary arteries: a patient-level pooled analysis of the DEBATE and ILIAS studies.

EuroIntervention 2021 Apr 2;16(18):e1503-e1510. Epub 2021 Apr 2.

Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.

Aims: Coronary flow reserve (CFR) is a physiological index for the assessment of myocardial flow impairment due to focal or microcirculatory coronary artery disease (CAD). Coronary flow capacity (CFC) is another flow-based concept in diagnosing ischaemic heart disease, based on hyperaemic average peak velocity (hAPV) and CFR. We evaluated clinical and haemodynamic factors which potentially influence CFR and CFC in non-obstructed coronary arteries.

Methods And Results: Intracoronary Doppler flow velocity measurements to obtain CFR and CFC were performed after inducing hyperaemia in 390 non-obstructed vessels of patients who were scheduled for elective percutaneous coronary intervention (PCI) of another vessel. Akaike's information criterion (AIC) revealed age, female gender, history of myocardial infarction, hypercholesterolaemia, diastolic blood pressure, oral nitrates and rate pressure product as independent predictors of CFR and CFC. After regression analysis, age and female gender were associated with lower CFR and age was associated with worse CFC in angiographically non-obstructed vessels.

Conclusions: Age and female gender are associated with lower CFR, and age with worse CFC in an angiographically non-obstructed coronary artery. CFC seems to be less sensitive to variations in clinical and haemodynamic parameters than CFR and is therefore a promising tool in contemporary clinical decision making in the cardiac catheterisation laboratory.
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http://dx.doi.org/10.4244/EIJ-D-19-00774DOI Listing
April 2021

Contribution of Age-Related Microvascular Dysfunction to Abnormal Coronary: Hemodynamics in Patients With Ischemic Heart Disease.

JACC Cardiovasc Interv 2020 01;13(1):20-29

Amsterdam UMC, University of Amsterdam, Heart Center, Department of Interventional Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.

Objectives: This study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis.

Background: Impairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function.

Methods: Intracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients). In 172 patients, Doppler measurements were also performed in unobstructed vessels. Associations of coronary hemodynamics with aging were studied in both the stenosed and unobstructed arteries.

Results: Aging was associated with a progressive increase in minimal microvascular resistance and a progressive decrease in hyperemic flow in both obstructed and nonobstructed coronary arteries. As such, coronary flow reserve decreased with advancing age. Epicardial stenosis severity assessed by resting Pd/Pa, basal stenosis resistance index, and hyperemic stenosis resistance index was equivalent across age groups. By contrast, fractional flow reserve increased with advancing age. Consequently, the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of concomitant focal epicardial and diffuse or microvascular disease (relative risk: 1.6; 95% confidence interval: 1.1 to 2.3; p = 0.017) increased with advancing age, whilst the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of non-flow-limiting stenosis with a healthy microcirculation decreased (relative risk: 0.7; 95% CI: 0.5 to 1.0; p = 0.022).

Conclusions: Aging is associated with progressive pan-myocardial impairment of coronary vasodilatory capacity due to an increase in minimal microvascular resistance. Concomitant aging-related impairment in microvascular function impacts the pathophysiology of ischemic heart disease in the individual patient and is not adequately identified by hyperemic coronary pressure measurements alone.
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http://dx.doi.org/10.1016/j.jcin.2019.08.052DOI Listing
January 2020

Artificial Intelligence for Aortic Pressure Waveform Analysis During Coronary Angiography: Machine Learning for Patient Safety.

JACC Cardiovasc Interv 2019 10 25;12(20):2093-2101. Epub 2019 Sep 25.

Department of Cardiology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

Objectives: This study developed a neural network to perform automated pressure waveform analysis and allow real-time accurate identification of damping.

Background: Damping of aortic pressure during coronary angiography must be identified to avoid serious complications and make accurate coronary physiology measurements. There are currently no automated methods to do this, and so identification of damping requires constant monitoring, which is prone to human error.

Methods: The neural network was trained and tested versus core laboratory expert opinions derived from 2 separate datasets. A total of 5,709 aortic pressure waveforms of individual heart beats were extracted and classified. The study developed a recurrent convolutional neural network to classify beats as either normal, showing damping, or artifactual. Accuracies were reported using the opinions of 2 independent core laboratories.

Results: The neural network was 99.4% accurate (95% confidence interval: 98.8% to 99.6%) at classifying beats from the testing dataset when judged against the opinions of the internal core laboratory. It was 98.7% accurate (95% confidence interval: 98.0% to 99.2%) when judged against the opinions of an external core laboratory not involved in neural network training. The neural network was 100% sensitive, with no beats classified as damped misclassified, with a specificity of 99.8%. The positive predictive and negative predictive values were 98.1% and 99.5%. The 2 core laboratories agreed more closely with the neural network than with each other.

Conclusions: Arterial waveform analysis using neural networks allows rapid and accurate identification of damping. This demonstrates how machine learning can assist with patient safety and the quality control of procedures.
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http://dx.doi.org/10.1016/j.jcin.2019.06.036DOI Listing
October 2019

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

Diastolic-systolic velocity ratio to detect coronary stenoses under physiological resting conditions: a mechanistic study.

Open Heart 2019;6(1):e000968. Epub 2019 Mar 1.

Imperial College London, London, UK.

Objective: Diastolic-systolic velocity ratio (DSVR) is a resting index to assess stenoses in the left anterior descending artery (LAD). DSVR can be measured by echocardiographic or intracoronary Doppler flow velocity. The objective of this cohort study was to elucidate the fundamental rationale underlying the decreased DSVR in coronary stenoses.

Methods: In cohort 1, simultaneous measurements of intracoronary Doppler flow velocity and pressure were acquired in the LAD of 228 stable patients. Phasic stenosis resistance, microvascular resistance and total vascular resistance (defined as stenosis and microvascular resistance combined) were studied during physiological resting conditions. Stenoses were classified according to severity by strata of 0.10 fractional flow reserve (FFR) units.

Results: DSVR was decreased in stenoses with lower FFR. Stenosis resistance was equal in systole and diastole for every FFR stratum. Microvascular resistance was consistently higher during systole than diastole. In lower FFR strata, stenosis resistance as a percentage of the total vascular resistance increases both during systole and diastole. The difference between the stenosis resistance as a percentage of total vascular resistance during systole and diastole increases for lower FFR strata, with an accompanying rise in diastolic-systolic resistance ratio. A significant inverse correlation was observed between DSVR and the diastolic-systolic resistance ratio (r=0.91, p<0.001). In cohort 2 (n=23), DSVR was measured both invasively and non-invasively by transthoracic echocardiography, yielding a good correlation (r=0.82, p<0.001).

Conclusions: The rationale by which DSVR is decreased distal to coronary stenoses is dependent on a comparatively higher influence of the increased stenosis resistance on total vascular resistance during diastole than systole.
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http://dx.doi.org/10.1136/openhrt-2018-000968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443135PMC
February 2021

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

Relationship between FFR, CFR and coronary microvascular resistance - Practical implications for FFR-guided percutaneous coronary intervention.

PLoS One 2019 7;14(1):e0208612. Epub 2019 Jan 7.

CREATIS, INSERM U1206, Université Lyon 1, INSA Lyon, Villeurbanne, France.

Objective: The aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.

Methodology: FFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.

Results: Hyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x - 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.

Conclusion: The FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208612PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322913PMC
September 2019

Pressure-derived estimations of coronary flow reserve are inferior to flow-derived coronary flow reserve as diagnostic and risk stratification tools.

Int J Cardiol 2019 Mar 7;279:6-11. Epub 2018 Nov 7.

Heart Center, Amsterdam UMC, AMC, Amsterdam, the Netherlands.

Background: Pressure-derived coronary flow reserve (CFR) and pressure-bounded CFR (CFR) enable simple estimation of CFR from routine pressure measurements, but have been inadequately validated. We sought to compare CFR and CFR against flow-derived CFR (CFR) in terms of diagnostic accuracy, as well as regarding their comparative prognostic relevance.

Methods: We evaluated 453 intermediate coronary lesions with intracoronary pressure and flow measurements. CFR was defined as hyperemic flow/baseline flow. The lower bound (CFR) and upper bound of CFR were defined as √[(ΔP) / (ΔP)] and [(ΔP) / (ΔP)], respectively. Long-term follow-up (median: 11.8-years) was performed in 153 lesions deferred from treatment to document the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, myocardial infarction and target vessel revascularization. CFR < 2.0 was considered abnormal.

Results: CFR was normal or abnormal in 56.7% of stenoses, and indeterminate in 43.3% of stenoses. There was a poor diagnostic agreement between CFR and CFR with CFR (overall agreement: 45.5% and 71.6% of vessels, respectively). There was equivalent risk for long-term MACE for lesions with abnormal versus normal CFR (Breslow p = 0.562), whereas vessels with abnormal CFR were significantly associated with increased long-term MACE (Breslow p < 0.001). For vessels where CFR was abnormal or normal, there was equivalent risk for long-term MACE for vessels with abnormal versus normal CFR (Breslow p = 0.194), whereas vessels with abnormal CFR were associated with increased MACE rates over time (Breslow p < 0.001).

Conclusions: Pressure-derived estimations of CFR poorly agree with flow-derived measurements of CFR, which may explain the inferior association with long-term MACE as compared to flow-derived CFR.
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http://dx.doi.org/10.1016/j.ijcard.2018.11.013DOI Listing
March 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

Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial.

BMJ 2018 Oct 2;363:k3793. Epub 2018 Oct 2.

Thoraxcenter, Erasmus Medisch Centrum, Rotterdam, Netherlands.

Objective: To show that limiting dual antiplatelet therapy (DAPT) to six months in patients with event-free ST-elevation myocardial infarction (STEMI) results in a non-inferior clinical outcome versus DAPT for 12 months.

Design: Prospective, randomised, multicentre, non-inferiority trial.

Setting: Patients with STEMI treated with primary percutaneous coronary intervention (PCI) and second generation zotarolimus-eluting stent.

Participants: Patients with STEMI aged 18 to 85 that underwent a primary PCI with the implantation of second generation drug-eluting stents were enrolled in the trial. Patients that were event-free at six months after primary PCI were randomised at this time point.

Interventions: Patients that were taking DAPT and were event-free at six months were randomised 1:1 to single antiplatelet therapy (SAPT) (ie, aspirin only) or to DAPT for an additional six months. All patients that were randomised were then followed for another 18 months (ie, 24 months after the primary PCI).

Main Outcome Measures: The primary endpoint was a composite of all cause mortality, any myocardial infarction, any revascularisation, stroke, and thrombolysis in myocardial infarction major bleeding at 18 months after randomisation.

Results: A total of 1100 patients were enrolled in the trial between 19 December 2011 and 30 June 2015. 870 were randomised: 432 to SAPT versus 438 to DAPT. The primary endpoint occurred in 4.8% of patients receiving SAPT versus 6.6% of patients receiving DAPT (hazard ratio 0.73, 95% confidence interval 0.41 to 1.27, P=0.26). Non-inferiority was met (P=0.004 for non-inferiority), as the upper 95% confidence interval of 1.27 was smaller than the prespecified non-inferiority margin of 1.66.

Conclusions: DAPT to six months was non-inferior to DAPT for 12 months in patients with event-free STEMI at six months after primary PCI with second generation drug-eluting stents.

Trial Registration: Clinicaltrials.gov NCT01459627.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167608PMC
http://dx.doi.org/10.1136/bmj.k3793DOI Listing
October 2018

Paclitaxel-eluting balloon versus everolimus-eluting stent in patients with diabetes mellitus and in-stent restenosis: Insights from the randomized DARE trial.

Catheter Cardiovasc Interv 2019 02 19;93(2):216-221. Epub 2018 Sep 19.

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

Objectives: To investigate the relative performance of treatment with a paclitaxel-eluting balloon (PEB) compared with an everolimus-eluting stent (EES) for in-stent restenosis (ISR) in patients with diabetes mellitus (DM).

Background: ISR remains a challenge in contemporary clinical practice, particularly in patients with DM.

Methods: In the multicenter randomized DARE trial, patients with BMS or DES ISR were randomized in a 1:1 fashion to treatment with a PEB or an EES. Patients underwent angiographic follow-up after 6 months. For the purpose of this analysis, the relative performance of PEB versus EES in diabetic patients was investigated.

Results: Of 278 patients enrolled in DARE, 88 (32%) had DM, of whom 46 were randomized to EES and 42 to PEB treatment. Of patients with DM, 48 (55%) had DES-ISR. Angiographic follow-up was available in 30 patients (72%) in the PEB group and 36 patients (78%) in the DES group. There were no differences in terms of 6-months minimal lumen diameter in diabetic patients treated with EES (1.46 ± 0.66 mm) versus PEB (1.78 ± 0.58 mm, P = 0.15). Adverse events at one year follow-up were similar in both groups, with Major Adverse Events (MAE, death, target vessel MI, or TVR) occurring in 17.4% in the EES group versus 11.9% in the PEB group, P = 0.44.

Conclusions: In patients with ISR and DM, use of a PEB resulted in similar 6-months in-segment minimal lumen diameter and comparable rates of MAE. In-segment late loss at 6 months was significantly lower in the PEB arm. Although larger trials in DM patients with ISR are necessary, PEB is a promising treatment option obviating the need for additional stent implantation.
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http://dx.doi.org/10.1002/ccd.27814DOI Listing
February 2019

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

JACC Cardiovasc Interv 2018 08;11(15):1437-1449

Klinikum Oldenburg, European Medical School, Carl von Ossietzky University, Oldenburg, Germany.

Objectives: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS).

Background: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization.

Methods: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year.

Results: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04).

Conclusions: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.
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http://dx.doi.org/10.1016/j.jcin.2018.05.029DOI Listing
August 2018

Comprehensive physiological evaluation of epicardial and microvascular coronary domains using vascular conductance and zero flow pressure.

EuroIntervention 2019 Feb 8;14(15):e1593-e1600. Epub 2019 Feb 8.

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

Aims: Assessment of the coronary circulation has been based largely on pressure ratios (epicardial) and resistance (micro-vessels). Simultaneous assessment of epicardial (CEPI) and microvascular conductance (CMICRO) provides an intuitive approach using the same units for both coronary domains and expressing the actual deliverability of blood. The aim of this study was to develop a novel integral method for assessing the functional severity of epicardial and microvascular disease.

Methods And Results: We performed intracoronary pressure and Doppler flow velocity measurements in 403 vessels in 261 patients with stable coronary artery disease. Hyperaemic mid-to-late diastolic pressure and flow velocity (PV) relationships were calculated. The slope of the aortic PV indicates the overall conductance and the slope of the distal PV relationship represents CMICRO. The intercept with the x-axis represents zero-flow pressure (Pzf). CEPI was derived from microvascular and overall conductance. Median CEPI was higher compared to CMICRO (4.2 [2.1-8.0] versus 1.3 [1.0-1.7] cm/s/mmHg, p<0.001). CMICRO was independent of stenosis severity (1.3 [1.0-1.7] in FFR ≤0.80 versus 1.4 [1.0-1.8] in FFR >0.8, p=0.797). ROC curves (using FFR and HSR concordant vessels as standard) demonstrated an excellent ability of CEPI to characterise significant stenoses (AUC 0.93). When CEPI
Conclusions: A comprehensive assessment of separate CEPI and CMICRO was feasible. CEPI has a remarkable diagnostic efficiency to detect a clinically relevant stenosis. When CEPI
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February 2019

Impact of Routine Invasive Physiology at Time of Angiography in Patients With Multivessel Coronary Artery Disease on Reclassification of Revascularization Strategy: Results From the DEFINE REAL Study.

JACC Cardiovasc Interv 2018 02;11(4):354-365

Department of Cardiovascular Sciences, Policlinico Umberto I Roma, Rome, Italy. Electronic address:

Objectives: This study sought to prospectively assess the impact of routine invasive physiology at the time of angiography on reclassification of therapeutic management of multivessel disease (MVD) patients, and to assess how implementation of instantaneous wave-free ratio (iFR) alters the process.

Background: Routine invasive physiology in intermediate coronary lesions at the time of diagnostic angiography, primarily in patients with single-vessel disease and using fractional flow reserve (FFR), reclassifies coronary revascularization management in 26% to 44% of patients. The role of invasive physiology in patients with MVD is unclear.

Methods: In 18 centers, 484 patients undergoing diagnostic angiography disclosing MVD with lesions >40% by visual assessment were included. Investigators were asked to prospectively define their initial management strategy based on angiography and clinical information. Invasive physiology (FFR or iFR driven) was then performed and final strategy defined. Initial and final vessel, patient, procedural, and overall management were described. Reclassification was defined as the difference between initial and final strategy.

Results: The majority of patients were clinically stable (82.2%). Two- and 3-vessel disease was present in 73.3% and 26.7% of patients, respectively. Lesions investigated were "intermediate" with median percent stenosis, median FFR, and median iFR at 60% (interquartile range [IQR]: 50% to 70%), 0.84 (IQR: 0.78 to 0.90), and 0.92 (IQR: 0.85 to 0.96), respectively. Vessel management was reclassified by physiology in 30.0% (249 of 828) of vessels. Patient and overall management were reclassified in 26.9% (130 of 484) and 45.7% (211 of 484) of patients, respectively. Reclassification rates were high irrespective of initial management (optimal medical therapy, percutaneous coronary intervention, or coronary artery bypass grafting), and performance and results of pre-procedural noninvasive tests. Reclassification of overall management in particular increased with the number of vessels investigated (1 vessel: 37.3%; 2 vessels: 45.0%; 3 vessels: 66.7%; p = 0.002). Incorporating iFR in the decision process was associated with investigation of more vessels (p = 0.04) and higher reclassification (p = 0.0001).

Conclusions: In patients with MVD and intermediate coronary lesions, invasive physiology at time of angiography reclassifies revascularization strategy in a large proportion of cases (26.9%) and investigation of more vessels is associated with higher reclassification rates.
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February 2018
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