Publications by authors named "P Damman"

134 Publications

Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial.

JACC Cardiovasc Imaging 2022 Apr 2. Epub 2022 Apr 2.

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

Objectives: The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on coronary vasomotor dysfunction (CVDys), as assessed by repeated coronary function testing (CFT), angina, and quality of life.

Background: Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of CVDys. However, studies substantiating its effect is this patient group are lacking.

Methods: A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36).

Results: In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36.

Conclusions: This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).
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http://dx.doi.org/10.1016/j.jcmg.2022.03.012DOI Listing
April 2022

Implementation of the ESC 0 h/1h algorithm and the HEART score in the emergency department: A prospective cohort study.

Int J Cardiol Heart Vasc 2022 Apr 2;39:100988. Epub 2022 Mar 2.

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

Background: The European Society of Cardiology (ESC) 0 h/1h algorithm is the preferred diagnostic strategy for chest pain patients in the emergency department (ED). It is suggested that adding clinical information to the algorithm improves its diagnostic performance. This study evaluates implementation of the ESC 0 h/1h algorithm in the ED and investigates the potential advantages of combining it with a clinical decision rule, which might be especially relevant in the heterogenous observation category.

Methods: In this prospective cohort study, chest pain patients in whom the ESC 0 h/1h algorithm was applied were enrolled. HEART score components were collected. Diagnostic characteristics were determined for the algorithm with and without addition of the HEART score. Primary endpoint was a composite endpoint at 30-day follow-up, consisting of myocardial infarction and death.

Results: A total of 668 patients were enrolled. The rule-in and rule-out categories consisted of 8.2% and 54.9% of the patients, respectively. Positive predictive value and specificity of the rule-in category were 67.3% and 97.1%, respectively. Negative predictive value (NPV) and sensitivity of the rule-out category were both 100%. In the observation category, a HEART score ≤ 3 yielded a NPV and sensitivity of 97.1% and 93.8%, respectively.

Conclusion: The ESC 0 h/1h algorithm yielded a NPV and sensitivity of 100% for myocardial infarction and death at 30-day follow-up. Addition of the HEART score did not provide clinically relevant advantages. Although the HEART score can be used to guide diagnostic testing in the observation category, a low HEART score did not yield an NPV of > 99%.
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http://dx.doi.org/10.1016/j.ijcha.2022.100988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897680PMC
April 2022

Relation Between Coronary Tortuosity and Vasomotor Dysfunction in Patients Without Obstructed Coronaries?

Front Cardiovasc Med 2021 13;8:804731. Epub 2022 Jan 13.

Radboudumc, Department of Cardiology, Nijmegen, Netherlands.

A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity. To investigate the association between CVDys and coronary tortuosity in patients with ANOCA All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography. In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively). In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.
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http://dx.doi.org/10.3389/fcvm.2021.804731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792852PMC
January 2022

Features of atherosclerosis in patients with angina and no obstructive coronary artery disease.

EuroIntervention 2022 Jan 27. Epub 2022 Jan 27.

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

Background: An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published.

Aims: This study aims to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm.

Methods: From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups, according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability.

Results: ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] versus 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm.

Conclusions: The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.
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http://dx.doi.org/10.4244/EIJ-D-21-00875DOI Listing
January 2022

Acetylcholine Rechallenge: A First Step Toward Tailored Treatment in Patients With Coronary Artery Spasm.

JACC Cardiovasc Interv 2022 01;15(1):65-75

Department of Cardiology and Angiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.

Objectives: The present study aimed to assess the feasibility and clinical value of acetylcholine (ACh) rechallenge for the detection of coexisting epicardial and microvascular spasm and to determine the efficacy of nitroglycerin in these spasm endotypes.

Background: The coexistence of epicardial and microvascular spasm is difficult to identify; thus, its frequency is unknown. Nitroglycerin treatment is equally recommended for both epicardial and microvascular coronary spasm despite contradictory data.

Methods: In this multicenter study, 95 patients with coronary spasm were included to undergo ACh rechallenge, which consisted of repeated ACh provocation 3 minutes after intracoronary nitroglycerin administration using the same dose that previously induced spasm.

Results: In total, 95 patients (age 61 ± 12 years, 69% female) were included. Fifty-five patients (58%) had microvascular spasm, and 40 patients (42%) had epicardial spasm during initial ACh provocation. In 48% of patients with epicardial spasm, ACh rechallenge revealed coexisting nitroglycerin-persistent microvascular spasm. Nitroglycerin administration before ACh rechallenge prevented reinducibility of epicardial spasm in all patients with focal spasm and in 80% of patients with diffuse spasm. Microvascular spasm was prevented in only 20% by prior nitroglycerin administration but was attenuated in another 49% of patients.

Conclusions: This study demonstrates a high frequency of epicardial spasm with coexisting nitroglycerin-persistent microvascular spasm. Intracoronary nitroglycerin was very effective in preventing reinducibility of epicardial spasm, whereas it prevented microvascular spasm in only 20% of patients. ACh rechallenge is a novel method that facilitates the detection of coexisting spasm endotypes and may pave the way towards tailored treatment of vasospastic angina.
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http://dx.doi.org/10.1016/j.jcin.2021.10.003DOI Listing
January 2022
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