Publications by authors named "Peter Damman"

80 Publications

Outpatient Management of Patients With Angina With No Obstructive Coronary Arteries: How to Come to a Proper Diagnosis and Therapy.

Front Cardiovasc Med 2021 2;8:716319. Epub 2021 Nov 2.

Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands.

Two-thirds of women and one-third of men who undergo a clinically indicated coronary angiography for stable angina, have no obstructive coronary artery disease (CAD). Coronary vascular dysfunction is a highly prevalent underlying cause of angina in these so called "Angina with No Obstructive Coronary Arteries (ANOCA)" patients, foremost in middle aged women. Coronary vascular dysfunction encompasses various endotypes, namely epicardial and microvascular coronary spasms, impaired vasodilatation, and increased microvascular resistance. ANOCA patients, especially those with underlying coronary vascular dysfunction, have an adverse cardiovascular prognosis, poor physical functioning, and a reduced quality of life. Since standard ischemia detection tests and coronary angiograms are not designed to diagnose coronary vascular dysfunction, this ischemic heart disease is often overlooked and hence undertreated. But adequate diagnosis is vital, so that treatment can be started to reduce symptoms, reduce healthcare costs and improve quality of life and cardiovascular prognosis. The purpose of this review is to give a contemporary overview of ANOCA with focus on coronary vascular dysfunction. We will provide a possible work-up of patients suspected of coronary vascular dysfunction in the outpatient clinical setting, based on the latest scientific insights and international consensus documents. We will discuss the value of ischemia detection testing, and non-invasive and invasive methods to diagnose coronary vascular dysfunction. Furthermore, we will go into pharmacological and non-pharmacological therapeutic options including anti-anginal regimens and lifestyle interventions.
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http://dx.doi.org/10.3389/fcvm.2021.716319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592903PMC
November 2021

Sex Differences in Coronary Function Test Results in Patient With Angina and Nonobstructive Disease.

Front Cardiovasc Med 2021 14;8:750071. Epub 2021 Oct 14.

Department of Cardiology, Radboudumc, Nijmegen, Netherlands.

Invasive coronary function testing (CFT) has become the recommended diagnostic tool to assess the various endotypes of coronary vasomotor dysfunction in patients with angina and no obstructive coronary artery disease (ANOCA), which has implications for therapy and prognosis. Although the expanding performance of CFT is leading to increased knowledge of coronary vasomotor dysfunction, little is known about sex-related differences in the results of comprehensive CFT. We conducted a prospective study of all consecutive patients with ANOCA that underwent clinically indicated CFT in a tertiary interventional from February 2019 to February 2021. CFT consisted of acetylcholine testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose CMD. CMD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) < 2.0. In total, 228 women and 38 men underwent CFT. No differences in traditional risk factors were seen, but women had a higher prevalence of migraine (45 vs. 14%, = 0.001). Men more often had a history of percutaneous coronary intervention (12 vs. 49%, = 0.001). We found no difference in clinical presentation. Coronary vasomotor dysfunction was present in 95% of men and 88% of women ( = 0.25), but males show more often epicardial spasm and less microvascular spasm than women (63 vs. 42% and 29 vs. 40% respectively, = 0.039). Impaired CFR was more prevalent among females (6 vs 20%, = 0.033). IMR [median of 23 (15-32) vs. 19 (13-25), = 0.08] did not differ between the sexes. Men undergoing CFT show a comparable prevalence of coronary vascular dysfunction as women. However, men have a higher prevalence of epicardial spasm and a lower prevalence of microvascular spasm compared with women. An impaired CFR was more often present in women, with an equally impairment of IMR.
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http://dx.doi.org/10.3389/fcvm.2021.750071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551605PMC
October 2021

Coronary CT angiography for improved assessment of patients with acute chest pain and low-range positive high-sensitivity troponins: study protocol for a prospective, observational, multicentre study (COURSE trial).

BMJ Open 2021 10 18;11(10):e049349. Epub 2021 Oct 18.

Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Introduction: Current evaluation of patients suspected of a non-ST-elevation acute coronary syndrome (NSTE-ACS) involves the use of algorithms that incorporate clinical information, electrocardiogram (ECG) and high-sensitivity cardiac troponins (hs-troponins). While primarily designed to rule out NSTE-ACS safely, these algorithms can also be used for rule in of NSTE-ACS in some patients. Still, in a substantial number of patients, these algorithms do not provide a conclusive work-up. These patients often present with an atypical clinical profile and low-range positive hs-troponin values without a characteristic rise or fall pattern. They represent a heterogeneous group of patients with various underlying conditions; only a fraction (30%-40%) will eventually be diagnosed with a myocardial infarction. Uncertainty exists about the optimal diagnostic strategy and their management depends on the clinical perspective of the treating physician ranging from direct discharge to admission for invasive coronary angiography. Coronary CT angiography (CCTA) is a non-invasive test that has been shown to be safe, fast and reliable in the evaluation of coronary artery disease. In this study, we will determine the usefulness of CCTA in patients with acute chest pain and low-range positive hs-troponin values.

Methods And Analysis: A prospective, double-blind, observational, multicentre study conducted in the Netherlands. Patients aged 30-80 years presenting to the emergency department with acute chest pain and a suspicion of NSTE-ACS, a normal or non-diagnostic ECG and low-range positive hs-troponins will be scheduled to undergo CCTA. The primary outcome is the diagnostic accuracy of CCTA for the diagnosis of NSTE-ACS at discharge, in terms of sensitivity and negative predictive value.

Ethics And Dissemination: This study was approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2017-506). Written informed consent to participate will be obtained from all participants. This study's findings will be published in a peer-reviewed journal.

Trial Registration Number: ClinicalTrials.gov (NCT03129659).
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http://dx.doi.org/10.1136/bmjopen-2021-049349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524275PMC
October 2021

Assessing Microvascular Dysfunction in Angina With Unobstructed Coronary Arteries: JACC Review Topic of the Week.

J Am Coll Cardiol 2021 Oct;78(14):1471-1479

Radboudumc, Nijmegen, the Netherlands. Electronic address:

Coronary microvascular dysfunction is a highly prevalent condition of both structural and functional coronary disorders in patients with angina and nonobstructive coronary artery disease (ANOCA). Current diagnostic modalities to assess microvascular function are related to prognosis, but these modalities have several technical shortcomings and lack the opportunity to determine true coronary blood flow and microvascular resistance. Intracoronary continuous thermodilution assessment of absolute coronary flow (Q) and microvascular resistance (R) was recently shown to be safe and feasible in ANOCA. Further exploration and implementation could lead to a better understanding and treatment of patients with ANOCA. This review discuss the coronary pathophysiology of microvascular dysfunction, provides an overview of noninvasive and invasive diagnostics, and focuses on the novel continuous thermodilution method. Finally, how these measurements of absolute Q and R could be integrated and how this would affect future clinical care are discussed.
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http://dx.doi.org/10.1016/j.jacc.2021.08.028DOI Listing
October 2021

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

Stress dynamic CT perfusion in the evaluation of acute coronary syndrome.

Eur Heart J 2021 May 17. Epub 2021 May 17.

Department of Medical Imaging and Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.

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http://dx.doi.org/10.1093/eurheartj/ehab259DOI Listing
May 2021

Quantification of Absolute Myocardial Flow and Resistance by Continuous Thermodilution in Patients with Ischemia and Nonobstructive Coronary Artery Disease (INOCA).

J Vis Exp 2021 04 24(170). Epub 2021 Apr 24.

Radboud University Medical Center;

In approximately half of the patients undergoing coronary angiography for angina pectoris or for signs or symptoms suggestive of ischemic heart disease, no obstructive coronary artery disease is angiographically visible. The majority of these patients with angina or ischemia and no obstructive coronary artery disease (INOCA) have an underlying coronary vasomotor dysfunction, and current consensus documents recommend diagnostic invasive coronary vasomotor function testing (CFT). During CFT, a variety of vasomotor dysfunction endotypes can be assessed, including vasospastic coronary dysfunction (epicardial or microvascular vasospasm), and/or microvascular vasodilatory dysfunction, including impaired vasodilatory capacity and increased microvascular resistance. The quantification of the continuous thermodilution derived absolute coronary blood flow and resistance might be a better measure compared to the currently used standard physiologic measures. This article provides an overview of this continuous thermodilution method.
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http://dx.doi.org/10.3791/62066DOI Listing
April 2021

Diagnostic necessity of cardiac MRI in myocardial infarction with no obstructive coronary arteries: an illustration.

Eur Heart J 2021 Apr 14. Epub 2021 Apr 14.

Department of Cardiology, Radboudumc, Nijmegen, Netherlands.

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http://dx.doi.org/10.1093/eurheartj/ehab195DOI Listing
April 2021

How is angina related to coronary microvascular dysfunction? A tip of the veil lifted.

Int J Cardiol 2021 07 9;334:26-27. Epub 2021 Apr 9.

Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.03.076DOI Listing
July 2021

Vasomotor dysfunction in patients with angina and nonobstructive coronary artery disease is dominated by vasospasm.

Int J Cardiol 2021 06 10;333:14-20. Epub 2021 Mar 10.

Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; University of Milano-Bicocca, Milan, Italy.

Background: Coronary vasomotor dysfunction, comprising endotypes of coronary spasm and/or impaired microvascular dilatation (IMD), is common in patients with angina and no obstructive coronary arteries (ANOCA). However, there are discrepant reports regarding the prevalence of these endotypes. The objective of this study was to determine the prevalence of coronary vasomotor dysfunction in patients with ANOCA, underlying endotypes, and differences in clinical characteristics.

Methods: Prospective registry of patients with ANOCA that underwent clinically indicated invasive coronary function testing (CFT), including acetylcholine spasm testing (2-200 μg) to diagnose coronary spasm, and adenosine testing (140 μg/kg/min) to diagnose IMD, defined as an index of microvascular resistance ≥25 and/or coronary flow reserve <2.0.

Results: Of the 111 patients that completed CFT (88% female, mean age 54 years), 96 (86%) showed vasomotor dysfunction. The majority 93 (97%) had coronary spasm, 63% isolated and 34% combined with IMD. Isolated IMD was rare, occurring in only 3 patients (3%). Hypertension was more prevalent in patients with vasomotor dysfunction compared to those without (39% vs. 7%, p = 0.02). Obesity and a higher severity of angiographic atherosclerotic disease were more prevalent in patients with coronary spasm compared to those without (61% vs. 28%; 40% vs. 0%, respectively, both p < 0.01). No differences in angina characteristics were observed between patients with and without vasomotor dysfunction or between endotypes.

Conclusions: Coronary vasomotor dysfunction is highly prevalent in patients with ANOCA, especially epicardial or microvascular vasospasm, whereas isolated IMD was rare. Performing a CFT without acetylcholine testing should be strongly discouraged.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.079DOI Listing
June 2021

Absolute Coronary Blood Flow Measured by Continuous Thermodilution in Patients With Ischemia and Nonobstructive Disease.

J Am Coll Cardiol 2021 02;77(6):728-741

Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Background: Intracoronary continuous thermodilution is a novel technique to quantify absolute coronary flow (Q) and resistance (R) and has potential advantages over current methods such as coronary flow reserve (CFR) and index of microvascular resistance (IMR). However, no data are available in patients with ischemia and nonobstructive coronary artery disease (INOCA).

Objectives: This study aimed to assess the relationship of Q and R with the established CFR/IMR in INOCA patients, to explore the potential of absolute Q, and to predict self-reported angina.

Methods: Consecutive INOCA patients (n = 84; 87% women; mean age 56 ± 8 years) underwent coronary function testing, including acetylcholine (ACH) provocation testing, adenosine (ADE) testing (CFR/IMR), and continuous thermodilution (absolute Q and R) with saline-induced hyperemia.

Results: ACH testing was abnormal (ACH+) in 87%, and ADE testing (ADE+) in 38%. The median absolute Q was 198 ml/min, and the median absolute R was 416 WU. The absolute R was higher in patients with ADE+ versus ADE- (495 WU vs. 375 WU; p = 0.04) but did not differ between patients with ACH+ versus ACH- (421 WU vs. 409 WU; p = 0.74). Low Q and high R were associated with severe angina (odds ratio: 3.09; 95% confidence interval: 1.16 to 8.28; p = 0.03; and odds ratio: 2.60; 95% confidence interval: 0.99 to 6.81; p = 0.05), respectively.

Conclusions: In this study, absolute R was higher in patients with abnormal CFR/IMR, whereas both Q and R were unrelated to coronary vasospasm. Q and R were associated with angina, although their exact predictive value should be determined in larger studies.
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http://dx.doi.org/10.1016/j.jacc.2020.12.019DOI Listing
February 2021

Pre-Emptive OCT-Guided Angioplasty of Vulnerable Intermediate Coronary Lesions: Results from the Prematurely Halted PECTUS-Trial.

J Interv Cardiol 2020 3;2020:8821525. Epub 2020 Dec 3.

Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands.

Objectives: To assess the safety and efficacy of pre-emptive treatment of optical coherence tomography- (OCT-) derived vulnerable, non-flow-limiting, non-culprit lesions in patients with myocardial infarction (MI).

Background: Intracoronary imaging with OCT can aid in the decision to treat non-flow-limiting lesions by identifying vulnerable plaques. Pre-emptive treatment of these lesions might improve patient outcome by "sealing" these plaques. Bioresorbable vascular scaffolds (BVS) have theoretical benefit for this treatment because they dissolve completely over time.

Methods: In patients presenting with MI, non-culprit lesions with a fractional flow reserve ≥0.8 were imaged with OCT. Vulnerable plaques were randomised to either percutaneous coronary intervention (PCI) with bioresorbable vascular scaffold (BVS) placement or optimal medicinal therapy (OMT). The primary outcome was a composite of all-cause mortality, non-fatal MI, and unplanned revascularisation at 1-year follow-up.

Results: The trial was stopped prematurely after retraction from the market of the Absorb BVS. At that time, a total of 34 patients were randomised. At two years, the composite endpoint occurred 3 times (18.8%) in the BVS group and 1 time (6.3%) in the OMT group. Apart from one elective PCI for stable angina in the OMT group, no target lesions in any group were revascularised.

Conclusions: Pre-emptive stenting of vulnerable plaques had no evident benefit compared to conservative treatment. However, due to the low number of included patients, no definite conclusions could be drawn. Identifying and potentially treating vulnerable plaques remains an important target for future research. This trial is registered under https://www.trialregister.nl/trial/NL4177 on 08-12-2015.
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http://dx.doi.org/10.1155/2020/8821525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737444PMC
April 2021

Antithrombotic PreTreatment and Invasive Strategies in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome.

J Clin Med 2020 Aug 9;9(8). Epub 2020 Aug 9.

Department of Cardiology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

In the current era, the antithrombotic treatment of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) includes standard aspirin, and one of the potent P2Y inhibitors ticagrelor or prasugrel. The optimal timing of ticagrelor has not been adequately studied, while prasugrel is only recommended after coronary angiography prior to PCI. The invasive strategy, including indication and timing of angiography, depends on risk stratification and a mortality benefit has been shown in selected high-risk NSTE-ACS undergoing early (<24 h) intervention.
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http://dx.doi.org/10.3390/jcm9082578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464603PMC
August 2020

Optimal Medical Therapy Prescription in Patients with Acute Coronary Syndrome in the Netherlands: A Multicenter Pilot Registry.

Am J Cardiovasc Drugs 2021 Mar;21(2):219-229

Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Unlike neighboring countries, the Netherlands does not have a national acute coronary syndrome (ACS) registry to evaluate quality of care.

Objective: We conducted a pilot registry in two hospitals to assess the prescription of guideline-recommended therapies in Dutch patients with ACS.

Methods: We included all consecutive patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (n = 1309) admitted to two Dutch percutaneous coronary intervention centers between March 2015 and February 2016. We collected follow-up medication use and reasons for discontinuation at discharge and 1, 6, and 12 months post-discharge. We assessed the use of optimal medical therapy (OMT), defined as the combined prescription of aspirin, P2Y12 inhibitors, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

Results: OMT prescription was 43.2% at discharge, 60.1% at 1 month, and 28.7% at 12 months. At 1 month, OMT prescription was significantly lower in patients with NSTEMI (51.8 vs. 65.7% for STEMI; p < 0.001). OMT prescription was lower in women (6 months: 55.4 vs. 62.0%, p = 0.036) and in elderly patients.

Conclusion: In this pilot study that aimed to extend a national Dutch ACS registry to patients with STEMI and NSTEMI, OMT prescription was comparable to that in other local registries, was lower in women and patients with NSTEMI, and decreased with increasing age.
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http://dx.doi.org/10.1007/s40256-020-00427-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956932PMC
March 2021

Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction.

Cardiovasc Res 2020 03;116(4):787-805

Department of Cardiology, Radboud University Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands.

Early mechanical reperfusion of the epicardial coronary artery by primary percutaneous coronary intervention (PCI) is the guideline-recommended treatment for ST-elevation myocardial infarction (STEMI). Successful restoration of epicardial coronary blood flow can be achieved in over 95% of PCI procedures. However, despite angiographically complete epicardial coronary artery patency, in about half of the patients perfusion to the distal coronary microvasculature is not fully restored, which is associated with increased morbidity and mortality. The exact pathophysiological mechanism of post-ischaemic coronary microvascular dysfunction (CMD) is still debated. Therefore, the current review discusses invasive and non-invasive techniques for the diagnosis and quantification of CMD in STEMI in the clinical setting as well as results from experimental in vitro and in vivo models focusing on ischaemic-, reperfusion-, and inflammatory damage to the coronary microvascular endothelial cells. Finally, we discuss future opportunities to prevent or treat CMD in STEMI patients.
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http://dx.doi.org/10.1093/cvr/cvz301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061278PMC
March 2020

Early intravenous beta-blockers in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A patient-pooled meta-analysis of randomized clinical trials.

Eur Heart J Acute Cardiovasc Care 2020 Aug 14;9(5):469-477. Epub 2019 Feb 14.

Department of Cardiology, Radboud University Medical Center, The Netherlands.

Background: Conflicting evidence is available on the efficacy and safety of early intravenous beta-blockers before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. We performed a patient-pooled meta-analysis of trials comparing early intravenous beta-blockers with placebo or routine care in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Aim: The aim of this study was to evaluate the clinical and safety outcomes of intravenous beta-blockers in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Methods: Four randomized trials with a total of 1150 patients were included. The main outcome was one-year death or myocardial infarction. Secondary outcomes included biomarker-based infarct size, left ventricular ejection fraction during follow-up, ventricular tachycardia, and a composite safety outcome (cardiogenic shock, symptomatic bradycardia, or hypotension) during hospitalization.

Results: One-year death or myocardial infarction was similar among beta-blocker (4.2%) and control patients (4.4%) (hazard ratio: 0.96 (95% confidence interval: 0.53-1.75, =0.90, =0%). No difference was observed in biomarker-based infarct size. One-month left ventricular ejection fraction was similar, but left ventricular ejection fraction at six months was significantly higher in patients treated with early intravenous beta-blockade (52.8% versus 50.0% in the control group, =0.03). No difference was observed in the composite safety outcome or ventricular tachycardia during hospitalization.

Conclusion: In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, the administration of early intravenous beta-blockers was safe. However, there was no difference in the main outcome of one-year death or myocardial infarction with early intravenous beta-blockers. A larger clinical trial is warranted to confirm the definitive efficacy of early intravenous beta-blockers.
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http://dx.doi.org/10.1177/2048872619830609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672673PMC
August 2020

Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry.

Eur Heart J Cardiovasc Pharmacother 2019 07;5(3):127-138

Department of Cardiology, Isala Klinieken, Dokter van Heesweg 2, Zwolle, The Netherlands.

Aims: Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes.

Methods And Results: Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14-0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor.

Conclusion: In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.
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http://dx.doi.org/10.1093/ehjcvp/pvy030DOI Listing
July 2019

Trends in optimal medical therapy prescription and mortality after admission for acute coronary syndrome: a 9-year experience in a real-world setting.

Eur Heart J Cardiovasc Pharmacother 2018 04;4(2):102-110

Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands.

Aims: Optimal medical therapy (OMT) is recommended in acute coronary syndrome (ACS) patients. Few studies present temporal trends of OMT prescription and its impact on outcomes in a real-world setting. We aimed to evaluate OMT prescription in a real-world ACS population and its relation to mortality during almost a decade.

Methods And Results: Consecutive ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (NSTEMI) patients (n = 9202) admitted to a single Dutch tertiary hospital between 2006 and 2014 were included and followed for drug prescription and mortality up to 1 year. Optimal medical therapy was defined as prescription of aspirin, P2Y12inhibitors, statin, beta-blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Optimal medical therapy prescription was 43.7% at discharge, 46.6% at 30-days, and 25.5% at 1-year. Optimal medical therapy prescription at discharge was lower among NSTEMI patients (34.5% vs. 49.2%, P < 0.001). Optimal medical therapy prescription at discharge, 30-days and 1-year and mortality outcomes did not change during the study period. After adjustment for baseline and admission characteristics, OMT at discharge was associated with a reduction in mortality in patients who survived hospitalization for the index event [adjusted hazard ratio: 0.66, 95% confidence interval (0.46-0.93)].

Conclusions: In this single-centre observational registry with >9000 patients reflecting almost a decade of ACS care, <50% of patients were on OMT at discharge. Prescription of OMT and mortality outcomes remained stable during the study period. After adjustment, OMT prescription at discharge was associated with reduced mortality in ACS survivors. Further contemporary randomized studies are warranted to determine the role of beta-blockers and ACEi/ARBs in ACS patients with preserved left ventricular ejection fraction.
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http://dx.doi.org/10.1093/ehjcvp/pvy005DOI Listing
April 2018

Transcatheter closure of an iatrogenic aorta-right ventricular fistula after transfemoral aortic valve implantation.

Eur Heart J Case Rep 2017 Dec 20;1(2):ytx019. Epub 2017 Dec 20.

Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, F3-155, 1105 AZ, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1093/ehjcr/ytx019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177075PMC
December 2017

Five-year follow-up of the endothelial progenitor cell capturing stent versus the paxlitaxel-eluting stent in de novo coronary lesions with a high risk of coronary restenosis.

Catheter Cardiovasc Interv 2018 06 4;91(7):1212-1218. Epub 2017 Sep 4.

Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Objectives: To assess the long-term safety and clinical efficacy of the Genous endothelial progenitor cell capturing stent (ECS) compared with the TAXUS Liberté paclitaxel-eluting stent (PES) in lesions with a high risk of restenosis.

Background: Instead of the use of cytotoxic or cytostatic drugs in drug-eluting stents, a "pro-healing" approach in ECS may overcome impeded healing response due to delayed functional endothelialization of the stent struts.

Methods: In the prospective, randomized TRIAS pilot study 193 patients with coronary artery lesions carrying a high risk of restenosis were included (ECS: n = 98, PES: n = 95). The primary focus of this analysis was target vessel failure (TVF) at 5 years. Dual antiplatelet therapy was prescribed for ≥1 month after ECS and for ≥6 months after PES.

Results: At 5 years follow-up, no significant differences were found in TVF (ECS 24% vs. PES 29%, risk difference 95% confidence interval (RDCI) -17.3% to 7.4%). Between 2 and 5 years after the index procedure, low numbers of TVF were observed in ECS compared with PES (ECS 4% vs. PES 16%, RDCI -20.8% to -2.3%). There was no definite stent thrombosis in ECS compared with four patients in the PES group.

Conclusion: This is the first randomized study providing very long-term clinical efficacy and safety of the ECS in lesions carrying a high risk of restenosis. At 5 years follow-up, TVF rates in ECS group are numerically lower compared with PES due to an increase of events between 2 and 5 years after the index procedure.
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http://dx.doi.org/10.1002/ccd.27249DOI Listing
June 2018

Timing of revascularisation for acute coronary syndrome.

Lancet 2017 08 1;390(10096):717-718. Epub 2017 Aug 1.

Heart Center, Academic Medical Center-University of Amsterdam, 1105 AZ Amsterdam, Netherlands.

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http://dx.doi.org/10.1016/S0140-6736(17)31632-XDOI Listing
August 2017

Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial.

J Am Coll Cardiol 2017 Apr;69(15):1883-1893

Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Background: The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years.

Objectives: The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T.

Methods: The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization.

Results: Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001).

Conclusions: In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients.
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http://dx.doi.org/10.1016/j.jacc.2017.02.023DOI Listing
April 2017

ST-elevation no myocardial infarction.

J Thromb Thrombolysis 2017 Apr;43(3):426-427

Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA.

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http://dx.doi.org/10.1007/s11239-016-1454-0DOI Listing
April 2017

Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes: a twelve-year experience from SWEDEHEART.

EuroIntervention 2016 Oct;12(9):1108-1116

Uppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Aims: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.

Methods And Results: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.

Conclusions: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.
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http://dx.doi.org/10.4244/EIJY15M11_05DOI Listing
October 2016

Older coronary thrombus is an independent predictor of 1-year mortality in acute myocardial infarction.

Eur J Clin Invest 2016 Jun 15;46(6):501-10. Epub 2016 Apr 15.

Department of Medical Sciences, Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Background: We have previously shown that older thrombus is associated with a twofold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients.

Methods: The study population (n = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (n = 870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models.

Results: Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1 year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement.

Conclusions: The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration.
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http://dx.doi.org/10.1111/eci.12619DOI Listing
June 2016

Influence of chronic kidney disease on anticoagulation levels and bleeding after primary percutaneous coronary intervention in patients treated with unfractionated heparin.

J Thromb Thrombolysis 2016 Apr;41(3):441-51

Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD-defined as creatinine clearance <60 ml/min). It is currently unknown at which UFH bolus dose persistent prolongation of activated partial thromboplastin time (aPTT) occurs in ST-segment elevation myocardial infarction (STEMI) patients with CKD. We investigated the effect of different UFH bolus doses on the first aPTT measured within 6 and 12 h after PPCI in 1071 STEMI patients with and without CKD undergoing primary percutaneous coronary intervention (PPCI) between 1-1-2003 and 31-07-2008. In the first 6 h after PPCI, aPTT ratio was 5.1 for patients with CKD versus 3.4 for those without (p < 0.001). The proportion of patients with markedly high aPTTs (aPTT ratio ≥ 4 times control) increased with increasing heparin bolus and beyond 130 IU/kg there was a marked difference between patients with and without CKD (74.1 and 42.3 % respectively, p < 0.001). By multivariable analysis, CKD was associated with an increased risk of markedly high aPTTs (odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.27-3.27), driven largely by an increased risk of aPTT prolongation in patients treated with UFH boluses ≥130 IU/kg (OR 3.69; 95 % CI 1.85-7.36; p for interaction = 0.009). In conclusion, CKD is associated with severe persistent aPTT prolongation in STEMI patients undergoing PPCI, possibly due to impaired plasma protein binding and reduced UFH elimination. A lower heparin bolus dose might result in lower aPTTs and less bleeding complications in patients with CKD undergoing PPCI.
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http://dx.doi.org/10.1007/s11239-015-1255-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799790PMC
April 2016

Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes.

Am Heart J 2014 Oct 13;168(4):522-9. Epub 2014 Jul 13.

Department of Cardiology and Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Background: A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS.

Methods: Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis.

Results: Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39).

Conclusions: In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.
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http://dx.doi.org/10.1016/j.ahj.2014.06.025DOI Listing
October 2014

Predictors and permanency of cardiac conduction disorders and necessity of pacing after transcatheter aortic valve implantation.

Pacing Clin Electrophysiol 2014 Nov 17;37(11):1520-9. Epub 2014 Jul 17.

Department of Cardiology, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands.

Background: Transcatheter aortic valve implantation (TAVI) with the Medtronic-CoreValve bioprosthesis (CoreValve Inc., Irvine, CA, USA) is associated with a high incidence of new-onset left bundle branch block (LBBB) and cardiac conduction disorders (CCDs) requiring permanent pacemaker (PPM) implantation. Our objective was to investigate the predictors and permanency of CCDs after TAVI and specifically to evaluate the necessity for pacing.

Methods: In this single-center study, we included patients who underwent TAVI with the Medtronic-CoreValve bioprosthesis. Electrocardiographic evaluation was performed pre- and post-TAVI and at follow-up. Pacemaker follow-up data were obtained and analyzed.

Results: We included 121 patients (age 81 ± 8 years). LBBB developed in 47 patients, for which prosthesis size (26 mm; odds ratio [OR]: 4.1, 95% confidence interval [CI]: 1.32-12.34, P = 0.01) and prosthesis depth (OR: 1.3, 95% CI: 1.09-1.57, P = 0.004) were independent predictors. In 19%, this new-onset LBBB was temporary. Requirement for a PPM occurred in 23 patients, for which mitral annular calcification (MAC; OR: 1.3, 95% CI: 1.05-1.56, P = 0.02) and preexisting right bundle branch block (RBBB; OR: 8.5, 95%CI: 1.61-44.91, P = 0.01) were independent predictors. At follow-up, 52% of the patients were continuously paced, but 22% of the patients had adequate atrioventricular conduction without the necessity for pacing. In the other 26% of the patients there was intermittent pacing.

Conclusion: There is a high incidence of new-onset LBBB and PPM implantation following TAVI with a Medtronic-CoreValve bioprosthesis. Prosthesis depth and size were predictors for new LBBB, while MAC and preexistent RBBB were predictors for PPM implantation. In approximately one fifth of the patients, new-onset LBBB and the necessity for pacing are only temporary.
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http://dx.doi.org/10.1111/pace.12460DOI Listing
November 2014
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