Faculty Bibliography

Therapeutic anticoagulation is essential to prevent and treat venous and arterial thromboembolism. The available agents target coagulation factors involved in thrombus formation but are associated with an increased risk of bleeding. Factor XI plays a minor role in haemostasis but contributes substantially to thrombus expansion, making it an attractive target to mitigate bleeding while maintaining antithrombotic efficacy. Various novel inhibitors, including antisense oligonucleotides, monoclonal antibodies and small molecules, have been developed. Phase II trials in orthopaedic surgery showed dose-dependent reductions in venous thromboembolism without significantly increasing bleeding compared with enoxaparin. In the first phase III trial of a small-molecule inhibitor of activated factor XI in patients with atrial fibrillation, asundexian was associated with a reduction in bleeding but also a higher risk of stroke, compared with apixaban. Factor XI inhibitors appear safe and hold promise for secondary prevention in myocardial infarction and ischaemic stroke, with ongoing phase III trials assessing their broader efficacy and safety. This Review discusses the rationale, pharmacology, evidence and future directions of factor XI inhibitors across various clinical settings.

BACKGROUND:Cardiogenic shock (CS) is a common complication of acute coronary syndrome (ACS) and is associated with significant morbidity and mortality. Revascularization has been shown to reduce mortality in ACS-CS. Patients with cancer are at high risk of ACS and CS. However, patients with cancer are often undertreated with invasive procedures and outcomes of patients with cancer and ACS-CS have not been thoroughly characterized. METHODS:Patients with ACS-CS from 2014 to 2020 with and without cancer were identified using the National Readmission Database (NRD). Primary outcome was death at 90-days. Secondary outcomes were 90-day cardiovascular (CV) and bleeding readmissions, and index hospitalization major bleeding and thrombotic complications. Patients with cancer were compared to patients without cancer using multivariable logistic and Cox proportional hazards regression. Temporal trends in revascularization among patients with and without cancer were examined. Effect of revascularization among patients with cancer and ACS-CS was assessed using propensity score weighting (PSW). RESULTS:A total of 140,205 patients were identified, of whom 6118 (4.4 %) with cancer were identified. Patients with cancer were less likely to undergo percutaneous coronary intervention (45.5 % vs 53.5 %) or be managed with mechanical circulatory support (36.6 % vs 46.0 %). After multivariable logistic regression, there was no difference in primary outcome (adjusted OR 0.98, 95 % CI 0.92-1.06) but patients with cancer had higher risk of 90-day CV (HR 1.11, 95 % CI 1.01-1.22) and bleeding readmissions (HR 1.39, 95 % CI 1.10-1.76). Among patients with cancer and ACS-CS, revascularization was associated with lower primary outcome (OR 0.54, 95 % CI 0.50-0.58) and 90-day CV readmission (HR 0.68, 95 % CI 0.59-0.77) after PSW. CONCLUSIONS:Among patients with ACS-CS, patients with cancer have similar 90-day death but higher risk of 90-day CV and bleeding readmissions. Additionally, revascularization was associated with improved outcomes among patients with cancer and ACS-CS. Further studies are needed to optimize patient selection for invasive management among patients with cancer.

BACKGROUND:The COMPLETE trial demonstrated a reduction in cardiovascular (CV) death or new myocardial infarction (MI) after complete, rather than culprit-only, revascularisation in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). However, it is unknown whether this benefit varies according to baseline left ventricular ejection fraction (LVEF). AIMS/OBJECTIVE:We aimed to determine the effects of complete versus culprit-only revascularisation according to LVEF. METHODS:Baseline LVEF was available for 2,214 of 4,041 randomised patients. The effect of both strategies on the first co-primary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischaemia-driven revascularisation (IDR) was determined within the prespecified LVEF ranges of <45% (N=660) and ≥45% (N=1,554). An analysis of clinical outcomes by LVEF according to thirds was also conducted. RESULTS:Patients with LVEF <45% experienced a significantly higher incidence of the first co-primary outcome compared with those with LVEF ≥45% (4.2%/year vs 2.8%/year; hazard ratio [HR] 1.51, 95% confidence interval [CI]: 1.15-1.98; p=0.003). Compared with a culprit-only strategy, complete revascularisation consistently reduced the first co-primary outcome in patients with LVEF <45% (3.0%/year vs 5.5%/year; HR 0.55, 95% CI: 0.36-0.86) and those with LVEF ≥45% (2.4%/year vs 3.2%/year; HR 0.74, 95% CI: 0.52-1.04; interaction p=0.31). Complete revascularisation also consistently reduced the second co-primary outcome in patients with LVEF <45% (3.5%/year vs 7.3%/year; HR 0.49, 95% CI: 0.33-0.74) and those with LVEF ≥45% (2.7%/year vs 6.3%/year; HR 0.44, 95% CI: 0.33-0.60; interaction p=0.67). Consistent results were observed for both co-primary outcomes when LVEF was further stratified into categories of LVEF ≤35%, 36-49% and ≥50%. CONCLUSIONS:Among patients presenting with STEMI and MVD, those with reduced LVEF are at higher risk of ischaemic events than patients with preserved LVEF. There is a consistent benefit of complete revascularisation regardless of baseline LVEF.

BACKGROUND:The volume of percutaneous coronary intervention (PCI) at ambulatory surgical centers (ASC) is expected to increase. METHODS:We surveyed US interventional cardiologists with a 58-question, anonymous online survey to evaluate their knowledge of and perspectives on ASC PCI. RESULTS:A total of 114 interventional cardiologists (9 fellows) responded. Participants were most commonly between 45 and 54 years old (33%). Most participants identified as male (95%), white (58%), non-Hispanic (95%), and with an academic affiliation (61%); 13 participants (11%) were PCI operators at an ASC. Most participants (59%) were in support of ASC PCI, 63% were very confident in their ability to decide if a patient is well-suited for ASC PCI, and 43% were not familiar with national and state-level laws/regulations of ASC PCI. Perceived benefits of ASC PCI included positive patient experience (69%), greater efficiency (79%), and lower costs for patients (50%) and institutions (53%). Participants reported a high level of concern about private equity involvement in ASC PCI (58%), occurrence of adverse events away from the hospital (47%), lower quality of care (39%), inappropriate patient selection (40%), inadequate regulatory standards (35%), and institutional pressures (47%). Supporters of ASC PCI reported a better self-assessed knowledge of it and perceived more benefits with fewer concerns. CONCLUSIONS:Most survey participants expressed support for ASC PCI, citing benefits such as improved patient experience, greater efficiency, and reduced costs. However, participants expressed concern for private equity involvement and the risk of adverse events occurring away from the hospital setting.

BACKGROUND:Increased vessel tortuosity may hinder the success of transradial procedures. Longer thin-walled, hydrophilic sheaths ≥ 75 cm can be placed into the ascending aorta and have the potential to avoid femoral access crossover. METHODS:We studied consecutive cases of patients undergoing left heart catheterization (LHC) where a 75 cm long thin-walled, hydrophilic sheath was used from 1/1/22 to 9/30/24. Patient and procedural characteristics were collected. Procedural data included indication, contrast load, radiation dose, procedural time, procedural complications, and the need to convert to femoral access. RESULTS:Our study sample included 71 patients (mean age 69, 45% male). Comorbidities included hypertension (82%), hyperlipidemia (76%), and congestive heart failure (30%). Previous coronary artery disease was present in 31% of patients, and 20% of patients had undergone previous percutaneous coronary intervention (PCI). Indications for LHC included symptoms of stable ischemic heart disease (21%), abnormal non-invasive ischemic testing (52%), acute coronary syndrome (18%), and pre-operative evaluation for surgery (8%). The reason to switch to the long thin-walled, hydrophilic sheath was inability to engage the coronaries due to subclavian/brachiocephalic artery tortuosity (86%) or radial artery spasm (14%). After switching to the long thin-walled, hydrophilic sheath, 62/71 (87%) cases successfully engaged the coronaries without converting to femoral access. The mean procedure time was 36 min for diagnostic LHC cases (n = 46) and 72 min for PCI cases (n = 25). No procedural complications occurred. CONCLUSION/CONCLUSIONS:This case series suggests that use of the long thin-walled, hydrophilic radial sheaths can avoid femoral access crossover in selected cases.

BACKGROUND:A contemporary, comprehensive risk score for the prediction of in-hospital fatal and nonfatal adverse events after percutaneous coronary intervention has been recently developed, albeit its external validation in patients with acute coronary syndrome is lacking. The objective of this study is to validate the Mayo Clinic integer risk score in a large cohort of patients with acute coronary syndrome undergoing percutaneous coronary intervention from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. METHODS:The risk score is composed of a common set of 23 clinical and procedural variables (model A) and 18 preprocedural variables (model B). The primary objective was to appraise the receiver-operator characteristics of both models for in-hospital mortality, bleeding, contrast-associated acute kidney injury, and stroke. The impact of risk score categories on 1-year outcomes was also investigated. RESULTS:Among the 6724 patients undergoing percutaneous coronary intervention in the MATRIX trial, the receiver-operator characteristics-area under the curves for in-hospital mortality, bleeding, contrast-associated acute kidney injury, and stroke were 0.88 (95% CI, 0.85-0.91), 0.66 (95% CI, 0.63-0.69), 0.70 (95% CI, 0.67-0.72), and 0.65 (95% CI, 0.52-0.78) for model A and 0.88 (95% CI, 0.84-0.92), 0.63 (95% CI, 0.60-0.66), 0.66 (95% CI, 0.63-0.69), and 0.65 (95% CI, 0.52-0.78) for model B, respectively. Mortality (model A), bleeding, and stroke risks were well calibrated, whereas mortality (model B) and contrast-associated acute kidney injury risk were underestimated. There was a gradual risk increase for 1-year mortality and bleeding as a function of the risk score tertile using both models. CONCLUSIONS:The risk score identifies patients with acute coronary syndrome at incremental risk of in-hospital mortality, bleeding, contrast-associated acute kidney injury, and stroke, representing a valuable tool for mitigation of modifiable risk factors. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01433627.

The reduction in bleeding and vascular complications in radial access compared with femoral access has been repeatedly demonstrated over the past decade of observational and randomized studies. This review summarizes the data and underscores the role of radial approach in reducing bleeding, vascular complications, and mortality in ST-segment elevation myocardial infarction. In addition, the review notes the potential for increased time to reperfusion and provides guidance on implementation of transradial primary percutaneous coronary interventions.

IMPORTANCE/UNASSIGNED:Previous data suggest that the time changes associated with daylight savings time (DST) may be associated with an increased incidence of acute myocardial infarction (AMI). OBJECTIVE/UNASSIGNED:To determine whether the incidence of patients presenting with AMI is greater during the weeks during or after DST and compare the in-hospital clinical events between the week before DST and after DST. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study examined patients enrolled in the Chest Pain MI Registry from 2013 to 2022. The study included patients who presented 1 week before DST, during the week of DST, or 1 week after DST (spring or fall) and assessed incidence of AMI, in-hospital mortality, stroke, and clinical outcomes during those times and compared the DST weeks with the week before or after. Data were analyzed from March 2024 to May 2025. MAIN OUTCOME AND MEASURE/UNASSIGNED:The main outcome was in-hospital mortality rate. The incidence ratio (IR) of AMI cases was calculated using the observed number of patients with AMI in the DST week divided by the number of patients with AMI who arrived 1 week before or after DST. RESULTS/UNASSIGNED:The final cohort included 168 870 patients (median [IQR] age, 65 [56-75] years, 57 023 females [33.8%]; 111 847 males [66.2%]) at 1124 hospitals during the study period. There were 28 678 patients (17.0%) with AMI treated during spring DST, 28 596 (16.9%) the week before, and 28 169 (16.7%) the week after. There were 27 942 patients (16.5%) with AMI treated during fall DST, 27 365 (16.2%) the week before, and 28 120 (16.7%) the week after. Patient characteristics were similar for the spring and fall DST analyses (spring and fall DST median [IQR] age across groups: 65 [56-74] years and 65 [56-75] years, respectively), and there were 28 725 females (33.6%) in the spring and 28 298 females (33.9%) in the fall. There was no significant difference in the incidence of AMI for the following time periods: spring DST week vs 1 week prior, spring DST week vs 1 week after, fall DST week vs 1 week prior, and fall DST week vs 1 week after. There were no significant differences in adjusted in-hospital outcomes for the 1 week before or after fall or spring DST. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study found no significant difference in the incidence rates of AMI in DST weeks compared with the week before or after. Additionally, there were no differences in in-hospital clinical outcomes.

BACKGROUND/UNASSIGNED:Studies suggest percutaneous coronary intervention (PCI) guided by intracoronary imaging (ICI) results in larger balloon/stent diameters and longer stents. Whether this occurs in real-world PCI is poorly understood. METHODS/UNASSIGNED:De novo PCIs performed at 48 nonfederal Michigan hospitals between July 2019 and June 2022 were evaluated with regression modeling to evaluate associations between ICI-guided PCI and balloon/stent dimensions. The association between ICI-guided PCI and coronary dissection/perforation was assessed using adjusted odds ratios. RESULTS/UNASSIGNED:=0.33 for trend, respectively). CONCLUSIONS/UNASSIGNED:In real-world practice, ICI-guided PCI was associated with larger stent/balloon diameters and longer stents. While ICI use was associated with dissections and perforations, there was no significant increase in the rate of these complications despite significant increases in ICI use and stent/balloon sizes during the study period. Further research is needed to evaluate the association between ICI use and procedural complications.