Gladys N. Janssens

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

BACKGROUND Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated. HYPOTHESIS We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI. DESIGN In a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment. SUMMARY The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival.

Rationale and design of the Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) trial

Background Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off‐target properties, such as improved endothelial‐dependent vasomotion and increased adenosine plasma levels. Methods The HI‐TECH study (NCT02587260) is a multinational, randomized, open‐label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5‐day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty‐six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group. Conclusion The HI‐TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post‐ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Effects of Ticagrelor, Prasugrel, or Clopidogrel at Steady State on Endothelial Function

Ticagrelor is a nonthienopyridine direct and reversible P2Y12 platelet receptor antagonist, and unlike prasugrel or clopidogrel inhibits, at least partially, the sodium-independent equilibrative nucleoside transporter 1 [(1)][1]. This ticagrelor-mediated off-target effect has potential to improve

Body Mass Index Is Associated With Microvascular Endothelial Dysfunction in Patients With Treated Metabolic Risk Factors and Suspected Coronary Artery Disease

Background Obesity is key feature of the metabolic syndrome and is associated with high cardiovascular morbidity and mortality. Obesity is associated with macrovascular endothelial dysfunction, a determinant of outcome in patients with coronary artery disease. Here, we compared the influence of obesity on microvascular endothelial function to that of established cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolemia, and smoking in patients with suspected coronary artery disease. Methods and Results Endothelial function was assessed during postocclusive reactive hyperemia of the brachial artery and downstream microvascular beds in 108 patients who were scheduled for coronary angiography. In all patients, microvascular vasodilation was assessed using peripheral arterial tonometry; laser Doppler flowmetry and digital thermal monitoring were performed. Body mass index was significantly associated with decreased endothelium‐dependent vasodilatation measured with peripheral arterial tonometry (r=0.23, P=0.02), laser Doppler flowmetry (r=0.30, P<0.01), and digital thermal monitoring (r=0.30, P<0.01). In contrast, hypertension, hypercholesterolemia, and smoking had no influence on microvascular vasodilatation. Especially in diabetic patients, endothelial function was not significantly reduced (control versus diabetes mellitus, mean±SEM or median [interquartile range], peripheral arterial tonometry: 1.90±0.20 versus 1.67±0.20, P=0.19, laser Doppler flowmetry: 728% [interquartile range, 427–1110] versus 589% [interquartile range, 320–1067] P=0.28, and digital thermal monitoring: 6.6±1.0% versus 2.5±1.7%, P=0.08). In multivariate linear regression analysis, body mass index was the only risk factor that significantly attenuated endothelium‐dependent vasodilatation using all 3 microvascular function tests. Conclusions Higher body mass index is associated with reduced endothelial function in patients with suspected coronary artery disease, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.

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

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in developed countries. Both resuscitation care and intensive care management for patients after OHCA has notably improved over the years.

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

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.