Ventricular septal defect complicating acute myocardial infarction: diagnosis and management. A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the ESC Working Group on Cardiovascular Surgery.

Ventricular septal defects are a rare complication after acute myocardial infarction with a mortality close to 100% if left untreated. However, even surgical or interventional closure is associated with a very high mortality and currently no randomized controlled trials are available addressing the optimal treatment strategy of this disease. This state-of-the-art review and clinical consensus statement will outline the diagnosis, hemodynamic consequences and treatment strategies of ventricular septal defects complicating acute myocardial infarction with a focus on current available evidence and a focus on major research questions to fill the gap in evidence.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Percutaneous Device Closure of Paravalvular Leak: Combined Experience From the United Kingdom and Ireland.

BACKGROUND: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. METHODS: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. RESULTS: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002). CONCLUSION: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.

Geographical miss is associated with vulnerable plaque and increased major adverse cardiovascular events in patients with myocardial infarction.

OBJECTIVES: To determine the incidence, characteristics, and outcomes associated with geographical miss (GM) of plaque. BACKGROUND: GM describes plaques that are incompletely covered following stenting, with GM thought to be associated with worse clinical outcomes. However, the incidence and characteristics of intravascular ultrasound (IVUS)-defined GM plaques have never been studied and the relationship between GM with both short and long-term clinical events is unknown. METHODS: One hundred and seventy patients with stable angina (n = 100) or myocardial infarction (MI) (n = 70) underwent virtual-histology IVUS (VH-IVUS) prior to, and following, percutaneous coronary intervention (PCI). GM was defined as three consecutive uncovered VH frames, either proximal or distal to the stented segment with plaque burden >40%. MACE was defined as a composite of death, myocardial infarction, unplanned revascularization, or hospitalization for angina. RESULTS: In total, 245 plaques underwent PCI with 80 (32.7%) displaying evidence of GM (69 patients). GM was associated with increased plaque volume (p < 0.001), % necrotic core, and dense calcium (both p < 0.001) and VH-defined thin-cap fibroatheroma (VH-TCFA) (p = 0.01). GM was not associated with increased periprocedural MI (p = 0.15) or inflammatory cytokine release. At follow-up, 42 MACE occurred in 28 patients (median 1,115 days). MACE was attributable to 8/80 (10%) plaques with and 7/165 (4.2%) plaques without GM (log-rank p = 0.11). GM was associated with increased MACE in patients presenting with MI (p = 0.015), but not for those with stable angina (p = 0.94). CONCLUSIONS: GM is common after PCI and associated with more vulnerable plaque composition/subtype. GM may confer a worse prognosis in patients undergoing PCI for MI. © 2015 Wiley Periodicals, Inc.

Percutaneous Closure of Paravalvular Leaks: A Systematic Review.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with the implantation of mechanical or bioprosthetic surgical valves and more recently recognized with transcatheter aortic valves implantation (TAVI). A significant number of patients will present with symptoms of congestive heart failure or haemolytic anaemia due to PVL and need further surgical or percutaneous treatment. Until recently, surgery has been the only available therapy for the treatment of clinically significant PVLs despite the significant morbidity and mortality associated with re-operation. Percutaneous treatment of PVLs has emerged as a safe and less invasive alternative, with low complication rates and high technical and clinical success rates. However, it is a complex procedure, which needs to be performed by an experienced team of interventional cardiologists and echocardiographers. This review discusses the current understanding of PVLs, including the utility of imaging techniques in PVL diagnosis and treatment, and the principles, outcomes and complications of transcatheter therapy of PVLs.

Percutaneous closure of postinfarction ventricular septal defect: in-hospital outcomes and long-term follow-up of UK experience.

BACKGROUND: Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative. METHODS AND RESULTS: Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997-2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5-54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0-9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63-1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the following: age (hazard ratio [HR]=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003), creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes (HR=4.18; P=0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12; P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with survival. CONCLUSIONS: Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

BACKGROUND: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). METHODS: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. FINDINGS: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001). INTERPRETATION: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. FUNDING: Chief Scientist Office Scotland and British Heart Foundation.

Ischaemic heart disease - a selected review of recent developments.

PURPOSE OF REVIEW: The purpose of this review is to highlight important and interesting advances in the field of ischaemic heart disease that have occurred over the last 18 months. It is focused on research that is likely to lead to changes in clinical practice. RECENT FINDINGS: There is new evidence on appropriate pharmacotherapy during angioplasty in both stable and unstable patients. The use of pressure wire assessment has been shown to improve patient outcome. The management of patients with ST elevation myocardial infarction (STEMI) is likely to change with a reduction in the use of manual thrombectomy and an increase in the treatment of nonculprit disease. SUMMARY: The optimal duration of dual antiplatelet therapy in percutaneous coronary intervention remains an intensely debated topic with contradictory results from major trials. Pressure wire guided coronary intervention reduces the need for urgent revascularization. The use of fractional flow reserve computed tomography has the potential to revolutionize functional testing. The treatment of patients presenting with ST elevation myocardial infarction is likely to change dramatically. Heparin with bailout glycoprotein IIbIIIa-inhibitor (GPIIbIIIa-I) appears superior to bivalirudin alone, although there is no longer a role for routine manual thrombectomy. Multivessel PCI to establish complete revascularization may become the gold standard in patients presenting with STEMI, although larger trials are needed. Novel therapies are being devised for the treatment of patients with intractable angina, but further work is required in this area.

Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans.

BACKGROUND: Mitochondrial DNA (mtDNA) damage occurs in both circulating cells and the vessel wall in human atherosclerosis. However, it is unclear whether mtDNA damage directly promotes atherogenesis or is a consequence of tissue damage, which cell types are involved, and whether its effects are mediated only through reactive oxygen species. METHODS AND RESULTS: mtDNA damage occurred early in the vessel wall in apolipoprotein E-null (ApoE(-/-)) mice, before significant atherosclerosis developed. mtDNA defects were also identified in circulating monocytes and liver and were associated with mitochondrial dysfunction. To determine whether mtDNA damage directly promotes atherosclerosis, we studied ApoE(-/-) mice deficient for mitochondrial polymerase-γ proofreading activity (polG(-/-)/ApoE(-/-)). polG(-/-)/ApoE(-/-) mice showed extensive mtDNA damage and defects in oxidative phosphorylation but no increase in reactive oxygen species. polG(-/-)/ApoE(-/-) mice showed increased atherosclerosis, associated with impaired proliferation and apoptosis of vascular smooth muscle cells, and hyperlipidemia. Transplantation with polG(-/-)/ApoE(-/-) bone marrow increased the features of plaque vulnerability, and polG(-/-)/ApoE(-/-) monocytes showed increased apoptosis and inflammatory cytokine release. To examine mtDNA damage in human atherosclerosis, we assessed mtDNA adducts in plaques and in leukocytes from patients who had undergone virtual histology intravascular ultrasound characterization of coronary plaques. Human atherosclerotic plaques showed increased mtDNA damage compared with normal vessels; in contrast, leukocyte mtDNA damage was associated with higher-risk plaques but not plaque burden. CONCLUSIONS: We show that mtDNA damage in vessel wall and circulating cells is widespread and causative and indicates higher risk in atherosclerosis. Protection against mtDNA damage and improvement of mitochondrial function are potential areas for new therapeutics.

Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Left Atrial Appendage Occlusion: British Cardiovascular Intervention Society and British Heart Rhythm Society Position Statement.

Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.

Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.

BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

Towards evidence-based percutaneous coronary intervention: the René Laënnec lecture in clinical cardiology.

Percutaneous coronary intervention (PCI) has matured from a pioneering adventure focused on feasibility to a major sub-specialty delivering real clinical results to patients. Despite delivering reductions in mortality and morbidity in the field of acute coronary syndrome and overcoming in-stent restenosis, several challenges still remain. Firstly, we need to adhere to practices supported by established trials: data relating to PCI in stable angina and late reopening of occluded infarct-related vessels suggest that this is not always the case. Secondly, we must develop new trials asking clinically relevant questions in 'real-world' populations that are focused on patient-based outcomes. Finally, given the current global financial crisis, it is now more important than ever that we demonstrate cost-effectiveness in our clinical practice. In these turbulent times, we discuss the challenges ahead for PCI in its journey towards evidence-based practice.

Percutaneous Transcatheter Closure of Post-infarction Ventricular Septal Defect: An Alternative to Surgical Intervention.

Post-infarction ventricular septal defect is a mechanical complication of acute MI. The incidence of this complication is low in the primary percutaneous coronary intervention era. However, the associated mortality is very high at 94% with medical management alone. Open surgical repair or percutaneous transcatheter closure still has an in-hospital mortality >40%. Retrospective comparisons between both closure methods are limited by observation and selection bias. This review addresses the assessment and optimisation of patients prior to repair, the optimal timing of repair, and the limitations in current data. The review considers techniques for percutaneous closure, and finally considers the path that future research should take to improve outcomes for patients.

Percutaneous paravalvular leak closure after transcatheter aortic valve implantation: the international PLUGinTAVI Registry.

BACKGROUND: Data regarding the safety and long-term effectiveness of percutaneous closure of paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) are scarce. AIMS: This study aims to present a large multicentre international experience of percutaneous post-TAVI PVL closure. METHODS: All patients who underwent percutaneous post-TAVI PVL closure in 14 hospitals across Europe and North America between January 2018 and October 2022 were included. RESULTS: Overall, 45 patients (64% male) were enrolled. The median age was 80 years (75-84). Among them, 67% and 33% had self-expanding and balloon-expandable valve implantations, respectively. Baseline post-TAVI PVL was severe in 67% of cases and moderate in the rest. The time from index TAVI to PVL closure procedure was 16.1 (8.7-34.8) months. Most patients were in NYHA Class III and IV (73%) before the procedure, and 40% had referred hospitalisations for heart failure between TAVI and the PVL closure procedure. Successful PVL closure was achieved in 94%, reducing regurgitation to ≤mild in 91% and moderate in the rest. The Amplatzer Valvular Plug III was the most frequently used device (27 cases), followed by the Amplatzer Valvular Plug 4. The incidence of severe adverse events was 11%. None of the patients died during the index hospitalisation. During long-term follow-up (21.7±16.2 months), the all-cause mortality rate was 14%, and patients presented improvement in functional status and a significant reduction in the rate of hospitalisation for heart failure (from 40% to 6%). CONCLUSIONS: Percutaneous PVL closure is a feasible and safe option for treating post-TAVI leaks. Successful PVL reduction to mild or less could be associated with acute and long-lasting improvements in clinical outcomes.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).

Leukocyte telomere length is associated with high-risk plaques on virtual histology intravascular ultrasound and increased proinflammatory activity.

OBJECTIVE: Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. METHODS AND RESULTS: One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01-1.53; P=0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02-1.39; P=0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1ß and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. CONCLUSIONS: Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.

Percutaneous management of paravalvular leaks.

Paravalvular leak (PVL) is a challenging complication of valve replacement surgery that can cause heart failure and haemolysis. Surgical repair is the traditional treatment for severe, symptomatic PVL, but many patients with PVL fall into high-risk categories for redo surgery. Percutaneous techniques for closure of PVL have been increasingly refined over the last decade with availability of approved purpose-specific devices for closure. Percutaneous closure requires a heart team approach, with attention paid to appropriate preprocedural and periprocedural imaging to ensure a successful closure with minimal residual leak or complication. There are limited studies addressing the selection of a percutaneous approach to PVL. No randomised trials comparing surgical and percutaneous repair have been conducted. Large national registries from the UK and Ireland and from Spain have demonstrated that high rates of technical success can be achieved, with mortality comparable with surgical repair. Six retrospective studies comparing surgical and percutaneous approaches have been published. These broadly show comparable technical success between the interventions, with reduced short-term mortality among patients treated percutaneously. Long-term outcomes were similar between both treatment options. Percutaneous repair is an attractive treatment option in many patients due to its reduced invasiveness and quicker recovery period. However, more prospective studies are needed to validate its place in the armamentarium of the heart team.