Michael Magro

Background/Objectives: Despite progress in secondary prevention, people with chronic coronary syndrome (CCS) still face a residual risk of ischemic events. Antithrombotic therapy reduces this risk and helps stabilize chronic cardiovascular disease. Studies have shown that combining low-dose rivaroxaban with aspirin—an approach called dual-pathway inhibition (DPI)—can lower this risk and reduce major adverse cardiovascular events (MACEs). However, researchers have not yet gathered enough real-world data to confirm the efficacy and safety of this strategy. The DUTCH CCS registry aims to collect real-world data on how effective and safe low-dose rivaroxaban combined with aspirin is for patients with CCS in The Netherlands. The study aims to provide insights into the outcomes, benefits, and risks of DPI in a real-world setting, beyond the scope of controlled clinical trials. Methods: The DUTCH CCS registry operates as a national, multicenter, prospective observational study. It enrolls 1000 patients with CCS who receive rivaroxaban (2.5 mg twice daily) and aspirin (80 mg or 100 mg once daily). The study targets individuals at high ischemic risk due to coronary artery disease (CAD) and follows a single-arm design. Researchers will measure the primary efficacy endpoint by tracking MACEs, clinically driven coronary, peripheral, or carotid revascularization, and stent thrombosis over one year. They will assess the primary safety endpoint by recording major bleeding events at one year. The team will collect data at both 3-month and 1-year follow-ups. Conclusions: As an observational study, this registry is not designed to establish causality. However, it seeks to improve our understanding of how DPI performs in real-world secondary prevention for CCS patients. The results may help update treatment guidelines and inform clinical decisions in everyday practice.

Background Patients with non-obstructive coronary artery disease (NOCAD) experience psychological distress and are at risk for major adverse cardiac events with mortality (MACE). We examined the risk of psychosocial distress, including Type D personality, depressive symptoms, anxiety, positive mood, hostility, and health status fatigue and disease specific and generic quality of life for MACE in patients with NOCAD. Methods In the Tweesteden mild stenosis (TWIST) study, 546 patients with NOCAD were followed for 10 years to examine the occurrence of cardiac mortality, a major cardiac event, or non-cardiac mortality in the absence of a cardiac event. Cox proportional hazard models were used to examine the impact of psychosocial distress and health status on the occurrence of MACE while adjusting for age, sex, disease severity, and lifestyle covariates. Sex differences and interactions were explored. Results In total 19% of the patients (mean age baseline = 61, SD 9 years; 52% women) experienced MACE, with an annualized event rate (AER) of 20 events per 1,000 person-years, and a lower risk for women compared to men. Positive mood (HR 0.97, 95%CI 0.95-1.00), fatigue (HR 1.03, 95%CI 1.00-1.06), and physical limitation (HR 0.99, 95%CI 0.98-1.00) were associated with MACE in adjusted models. No significant interactions between sex and psychosocial factors were present. Depressive symptoms were predictive of MACE, but no longer after adjustment. Neither Type D personality, anxiety, hostility, mental health status, or angina frequency and stability were significantly associated with MACE. Conclusions In patients with NOCAD fatigue, low positive mood, and a lower physical limitation score were associated with MACE, without marked sex differences. Type D personality, psychosocial factors, and health status were not predictive of adverse outcomes. Reducing psychosocial distress is a valid intervention goal by itself, though it is less likely to affect MACE in patients with NOCAD.

ST-depression and T-wave inversion are frequently present on the post-resuscitation electrocardiogram (ECG). However, the prognostic value of ischaemic ECG patterns is unknown. In this post-hoc subgroup analysis of the Coronary Angiography after Cardiac arrest (COACT) trial, the first in-hospital post-resuscitation ECG in out-of-hospital cardiac arrest patients with a shockable rhythm was analysed for ischaemic ECG patterns. Ischaemia was defined as ST-depression of ≥0.1 mV, T-wave inversion in ≥2 contiguous leads, or both. The primary endpoint was 90-day survival. Secondary endpoints were rate of acute unstable lesions, levels of serum troponin-T, and left ventricular function. Of the 510 out-of-hospital cardiac arrest patients, 340 (66.7%) patients had ischaemic ECG patterns. Patients with ischaemic ECG patterns had a worse 90-day survival compared with those without [hazard ratio 1.51; 95% confidence interval (CI) 1.08–2.12; P = 0.02]. A higher sum of ST-depression was associated with lower survival (log-rank = 0.01). The rate of acute unstable lesions (14.5 vs. 15.8%; odds ratio 0.90; 95% CI 0.51–1.59) did not differ between the groups. In patients with ischaemic ECG patterns, maximum levels of serum troponin-T (μg/L) were higher [0.595 (interquartile range 0.243–1.430) vs. 0.359 (0.159–0.845); ratio of geometric means 1.58; 1.13–2.20] and left ventricular function (%) was worse (44.7 ± 12.5 vs. 49.9 ± 13.3; mean difference −5.13; 95% CI −8.84 to −1.42). Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival. Post-arrest ischaemic ECG patterns were associated with worse 90-day survival. A higher sum of ST-depression was associated with lower survival. Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival.

Background: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). Methods: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. Results: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9–16.5]; P =0.068; log rank- P =0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5–9.5]; P P P =0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50–30.72]; P =0.013). Conclusions: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02989740.

Background: In patients with out‐of‐hospital cardiac arrest without ST‐segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out‐of‐hospital cardiac arrest. Methods and Results: A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost‐prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND‐36 and collected at 12‐month follow‐up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P =0.86). Generalized linear model: (β, 0.991; 95% CI, 0.894–1.099; P =0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P <0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND‐36 questionnaire did not differ between both groups. Conclusions: The mean total costs between patients with out‐of‐hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl ; Unique identifier: NL4857.

The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99–10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12–12.34; P < 0.001). Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients. Study design and main results.

The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Despite achievement of optimal epicardial coronary flow in the majority of patients treated for ST-segment elevation myocardial infarction (STEMI) by primary percutaneous coronary intervention (PPCI), myocardial no-reflow is a common phenomenon occurring in 5 to 50% of patients. The no-reflow phenomenon is a predictor of infarct size and an independent predictor of mortality both in the short and long term. Prevention of no-reflow is therefore a crucial step in improving prognosis of patients with STEMI. Several strategies including pharmacological and mechanical ones have been developed to improve microvascular perfusion in the setting of a myocardial infarction. Prevention starts by conservation of the microvascular reserve especially in patients at high risk of acute coronary syndromes such as diabetes patients. Optimal glycaemic control and the use of statins have been shown to reduce no-reflow in this context. Reducing ischaemic time by shortening door to balloon times, administration of intracoronary GP IIb/IIIa antagonists during PPCI and the use of manual aspiration thrombectomy have been shown to result in better myocardial perfusion and improved clinical outcome in major trials. In this review we discuss some of these major trials and studies of other therapeutic options that aim to prevent the no-reflow phenomenon.