Acute coronary syndrome (ACS) mostly arises from so-called vulnerable coronary plaques, particularly prone for rupture. Vulnerable plaques comprise a specific type of plaque, called the thin-cap fibroatheroma (TFCA). A TCFA is characterized by a large lipid-rich necrotic core, a thin fibrous cap, inflammation, neovascularization, intraplaque hemorrhage, microcalcifications or spotty calcifications, and positive remodeling. Vulnerable plaques are often not visible during coronary angiography. However, different plaque features can be visualized with the use of intracoronary imaging techniques, such as intravascular ultrasound (IVUS), potentially with the addition of near-infrared spectroscopy (NIRS), or optical coherence tomography (OCT). Non-invasive imaging techniques, such as computed tomography coronary angiography (CTCA), cardiovascular magnetic resonance (CMR) imaging, and nuclear imaging, can be used as an alternative for these invasive imaging techniques. These invasive and non-invasive imaging modalities can be implemented for screening to guide primary or secondary prevention therapies, leading to a more patient-tailored diagnostic and treatment strategy. Systemic pharmaceutical treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Additionally, ongoing studies are investigating whether modification of vulnerable plaque features with local invasive treatment options leads to plaque stabilization and subsequent cardiovascular risk reduction.

Background: The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on Occlusions After STEMI) trial was the first and only randomized trial investigating chronic total occlusion (CTO) percutaneous coronary intervention (PCI) early after primary PCI for ST‐segment–elevation myocardial infarction, compared with medical therapy for the CTO. We performed a 10‐year follow‐up of EXPLORE to investigate long‐term safety and clinical impact of CTO PCI after ST‐segment–elevation myocardial infarction, compared with no‐CTO PCI. Methods and Results: In EXPLORE, 302 patients post‐ST‐segment–elevation myocardial infarction with concurrent CTO were randomized to CTO PCI within ≈1 week or no‐CTO PCI. We performed an extended clinical follow‐up for the primary end point of major adverse cardiac events, consisting of cardiovascular death, coronary artery bypass grafting, or myocardial infarction. Secondary end points included all‐cause death, angina, and dyspnea. Median follow‐up was 10 years (interquartile range, 8–11 years). The primary end point occurred in 25% of patients with CTO PCI and in 24% of patients with no‐CTO PCI (hazard ratio [HR], 1.11 [95% CI, 0.70–1.76]). Cardiovascular mortality was higher in the CTO PCI group (HR, 2.09 [95% CI, 1.10–2.50]), but all‐cause death was similar (HR, 1.53 [95% CI, 0.93–2.50]). Dyspnea relief was more frequent after CTO PCI (83% versus 65%, P =0.005), with no significant difference in angina. Conclusions: This 10‐year follow‐up of patients post‐ST‐segment–elevation myocardial infarction randomized to CTO PCI or no‐CTO PCI demonstrated no clinical benefit of CTO PCI in major adverse cardiac events or overall mortality. However, CTO PCI was associated with a higher cardiovascular mortality compared with no‐CTO PCI. Our long‐term data support a careful weighing of effective symptom relief against an elevated cardiovascular mortality risk in CTO PCI decisions. Registration: URL: https://www.trialregister.nl ; Unique identifier: NTR1108.

Patients with non-obstructive lipid-rich plaques (LRPs) on combined intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) are at high risk for future events. Local pre-emptive percutaneous treatment of LRPs with a paclitaxel-eluting drug-coated balloon (PE-DCB) may be a novel therapeutic strategy to prevent future adverse coronary events without leaving behind permanent coronary implants. In this pilot study, we aim to investigate the safety and feasibility of pre-emptive treatment with a PE-DCB of non-culprit non-obstructive LRPs by evaluating the change in maximum lipid core burden in a 4 mm segment (maxLCBImm4) after 9 months of follow up. Therefore, patients with non-ST-segment elevation acute coronary syndrome underwent 3-vessel IVUS-NIRS after treatment of the culprit lesion to identify additional non-obstructive non-culprit LRPs, which were subsequently treated with PE-DCB sized 1:1 to the lumen. We enrolled 45 patients of whom 20 patients (44%) with a non-culprit LRP were treated with PE-DCB. After 9 months, repeat coronary angiography with IVUS-NIRS will be performed. The primary endpoint at 9 months is the change in maxLCBImm4 in PE-DCB-treated LRPs. Secondary endpoints include clinical adverse events and IVUS-derived parameters such as plaque burden and luminal area. Clinical follow-up will continue until 1 year after enrollment. In conclusion, this first-in-human study will investigate the safety and feasibility of targeted pre-emptive PE-DCB treatment of LRPs to promote stabilization of vulnerable coronary plaque at risk for developing future adverse events.

Background: Chronic total coronary occlusions (CTO) substantially increase the risk for sudden cardiac death. Among patients with chronic ischemic heart disease at risk for sudden cardiac death, an implantable cardioverter defibrillator (ICD) is the favored therapy for primary prevention of sudden cardiac death. This study sought to investigate the impact of CTOs on the risk for appropriate ICD shocks and mortality within a nationwide prospective cohort. Methods and Results: This is a subanalysis of the nationwide Dutch‐Outcome in ICD Therapy (DO‐IT) registry of primary prevention ICD recipients in The Netherlands between September 2014 and June 2016 (n=1442). We identified patients with chronic ischemic heart disease (n=663) and assessed available coronary angiograms for CTO presence (n=415). Patients with revascularized CTOs were excluded (n=79). The primary end point was the composite of all‐cause mortality and appropriate ICD shocks. Clinical follow‐up was conducted for at least 2 years. A total of 336 patients were included, with an average age of 67±9 years, and 20.5% was female (n=69). An unrevascularized CTO was identified in 110 patients (32.7%). During a median follow‐up period of 27 months (interquartile range, 24–32), the primary end point occurred in 21.1% of patients with CTO (n=23) compared with 11.9% in patients without CTO (n=27; P =0.034). Corrected for baseline characteristics including left ventricular ejection fraction, and the presence of a CTO was an independent predictor for the primary end point (hazard ratio, 1.82 [95% CI, 1.03–3.22]; P =0.038). Conclusions: Within this nationwide prospective registry of primary prevention ICD recipients, the presence of an unrevascularized CTO was an independent predictor for the composite outcome of all‐cause mortality and appropriate ICD shocks.