Faculty Bibliography

IMPORTANCE/UNASSIGNED:Both myocardial infarction (MI) and anemia have deleterious effects on health-related quality of life (QOL). Red blood cell (RBC) transfusion may improve QOL after MI by relieving symptoms and/or increasing functional capacity. OBJECTIVE/UNASSIGNED:To evaluate whether a liberal transfusion strategy compared with a more restrictive transfusion strategy affects QOL in patients with MI and anemia. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This analysis of QOL as a prespecified secondary outcome of the Myocardial Ischemia and Transfusion (MINT) trial, a randomized clinical trial comparing a liberal vs restrictive RBC transfusion strategy, included participants from 144 sites across 6 countries. Hospitalized adults with acute MI and anemia (hemoglobin [Hb] less than 10 g/dL). The MINT trial randomized 3504 patients, and this analysis included those who had QOL data collected and those who died before the 30-day follow-up period. Data were collected from April 2017 to April 2023, and data were analyzed from February 2024 to January 2025. INTERVENTIONS/UNASSIGNED:The MINT trial randomized patients to a restrictive (Hb of 7 to 8 g/dL) or a liberal (Hb of less than 10 g/dL) RBC transfusion strategy. MAIN OUTCOMES AND MEASURES/UNASSIGNED:QOL was measured using the EQ-5D-5L 30 days after randomization. RESULTS/UNASSIGNED:Of 2844 included patients, 1551 (54.5%) were male, and the mean (SD) age was 71.9 (11.5) years. A total of 2525 (88.8%; 1254 [49.7%] in the restrictive group and 1271 [50.3%] in the liberal group) had QOL data, and 319 (11.2%) died before 30-day follow-up. Overall, there were no differences in mean or median scores for any EQ-5D-5L QOL outcome between assigned transfusion strategies at 30 days postrandomization. Although a higher percentage of patients in the liberal compared with the restrictive transfusion group reported no problems compared with any problem in usual activities (506 of 1268 [39.9%] vs 473 of 1247 [37.9%]), mobility (474 of 1270 [37.3%] vs 460 of 1254 [36.7%]), and self-care (858 of 1271 [67.5%] vs 803 of 1254 [64.0%]) domains, none of these differences were statistically significant. Adjusted mixed-effects linear regressions showed no association between assigned transfusion strategy and mean differences in any QOL outcome. Adjusted regressions in several prespecified subgroups showed an association between a liberal transfusion strategy and better QOL scores in domains related to functional capacity, but the effects were only statistically significant in patients with a history of heart failure (Health Today rating: β, 2.06 [95% CI, -0.23 to 4.35] vs -1.44 [95% CI, -3.81 to 0.92]; P = .04). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This secondary analysis of the MINT trial found that in patients with MI and anemia, a liberal transfusion strategy compared with a restrictive transfusion strategy did not affect QOL outcomes 30 days after randomization. This suggests that higher Hb levels maintained with RBC transfusion may not offer significant benefits to QOL overall in patients with MI and anemia. Additional studies may be useful for further examining and validating transfusion's effect on QOL in patients with MI and heart failure. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02981407.

BACKGROUND/UNASSIGNED:Injection of contrast media for rapid measurement of contrast fractional flow reserve (cFFR) obviates the side effects and time requirements of adenosine fractional flow reserve (aFFR) and improves diagnostic performance relative to nonhyperemic pressure ratios. However, studies of cFFR have had variable delivery of contrast. We evaluated the diagnostic performance of cFFR using an automated contrast injector with a standardized volume and rate of delivery of contrast to the reference standard aFFR. METHODS/UNASSIGNED:) and RXi/Navvus FFR microcatheter. The diagnostic performance of cFFR was assessed using a 0.83 cutoff value based on published literature. Optimal cFFR cutoffs were also determined and illustrated using Bland-Altman analysis. RESULTS/UNASSIGNED:A total of 192 lesions from 178 patients were included in the per-protocol analysis (69 with an aFFR ≤0.80 and 109 with an aFFR >0.80). Using a cFFR cutoff value of ≤0.83, the accuracy, sensitivity, and specificity of cFFR were 0.89 (95% CI, 0.83-0.93), 0.70 (95% CI, 0.58-0.81), and 0.99 (95% CI, 0.95-1.00), respectively. The mean difference between cFFR and aFFR was 0.05 (-0.04 to 0.13). A cFFR threshold of ≤0.85 had the highest accuracy in predicting aFFR ≤0.80 with accuracy, sensitivity, and specificity equaling 0.90 (95% CI, 0.84-0.94), 0.87 (95% CI, 0.77-0.94), and 0.91 (95% CI, 0.84-0.95), respectively. CONCLUSIONS/UNASSIGNED:cFFR utilizing standardized parameters for contrast delivery leads to clinically acceptable levels of diagnostic performance compared with traditional aFFR to identify physiologically significant intermediate lesions. Future data evaluating the impact on clinical outcomes of cFFR-guided percutaneous coronary intervention are warranted. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03557385.

BACKGROUND:Patients undergoing atrial fibrillation (AF) ablation have historically been hospitalized overnight or longer postprocedure. National rates of same-day discharge (SDD) following AF ablation remain unknown. METHODS AND RESULTS/RESULTS:<0.0001), surpassing overnight hospitalization in Q1 of 2021. The likelihood of SDD increased significantly over time (odds ratio [OR], 1.26 per quarter-year [95% CI, 1.26-1.26]) with substantial variation across hospitals (median OR, 4.12 [95% CI, 3.48-4.79]). Those discharged the same day were less likely of Black race (OR, 0.71 [95% CI, 0.65-0.78]) and to have persistent AF (OR, 0.85 [95% CI, 0.82-0.88]) and cardiomyopathy (OR, 0.87 [95% CI, 0.84-0.91]). In total, major and overall complication rates were 0.70% and 2.13%, respectively. Major and overall complication rates were 0.03% and 0.19% for SDD and 0.24% and 0.98%, respectively, for overnight hospitalization. CONCLUSIONS:Rates of SDD following AF ablation markedly increased over time, corresponding with onset of the COVID-19 pandemic, with substantial hospital variation. SDD patients had fewer comorbid conditions and were less likely to have persistent AF. Postprocedural complication rates with SDD were low and comparable with patients hospitalized overnight.

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:Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes. METHODS:This study analyzed 3,447 (98.4%) patients randomized in the MINT (Myocardial Ischemia and Transfusion) trial between April 2017 to April 2023. Outcomes for this analysis included 30-day death or recurrent MI, death, and major adverse cardiovascular events (MACE, a composite of death, MI, stroke, and ischemia-driven unscheduled revascularization). Machine learning methods were used to identify baseline patient characteristics that informed the individualized treatment effect of a restrictive versus liberal transfusion strategy for each patient. The expected population risk of an outcome under a scenario in which patients received their optimal treatment, as indicated by the individualized treatment effect, was contrasted with expected risks for universally applying a restrictive strategy or a liberal strategy to all patients. RESULTS:Baseline characteristics did not inform individualized treatment effects on 30-day death and death or MI, suggesting minimal heterogeneity in treatment effect on these outcomes. An algorithm for estimating the individualized treatment effect on 30-day MACE included 12 baseline factors. If all patients received the optimal treatment as indicated by their estimated individualized treatment effect, the predicted risk of 30-day MACE in the sample population was 15.2% (95% CI 14.2%-16.2%). This corresponded to 4.0 (difference: -4.0%, 95% CI -5.8, -2.1) and 2.3 (difference: -2.3%, 95% CI -3.7, -0.9) percentage point risk reductions compared to applying a restrictive or liberal strategy to everyone respectively. CONCLUSIONS:The MINT trial average treatment effect, favoring a liberal strategy, may be optimal to minimize risk of 30-day death and death or MI for acute MI patients with anemia represented in the MINT sample as no individualized treatment effects were estimated on these outcomes. However, individualized transfusion strategy decisions have potential to reduce risk of 30-day MACE. External validation of the MACE algorithm is required before clinical use. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, NCT02981407, https://clinicaltrials.gov/study/NCT02981407.

BACKGROUND/UNASSIGNED:Myocardial injury detected after percutaneous coronary intervention (PCI) is associated with increased mortality. Predictors of post-PCI myocardial injury are not well established. The long-term prognostic relevance of post-PCI myocardial injury remains uncertain. METHODS/UNASSIGNED:Consecutive adults aged ≥18 years with stable ischemic heart disease who underwent elective PCI at NYU Langone Health between 2011 and 2020 were included in a retrospective, observational study. Patients with acute myocardial infarction or creatinine kinase myocardial band (CKMB) or troponin concentrations >99% of the upper reference limit before PCI were excluded. All patients had routine measurement of CKMB concentrations at 1 and 3 hours post-PCI. Post-PCI myocardial injury was defined as a peak CKMB concentration >99% upper reference limit. Linear regression models were used to identify clinical factors associated with post-PCI myocardial injury. Cox proportional hazard models were generated to evaluate relationships between post-PCI myocardial injury and all-cause mortality at long-term follow-up. RESULTS/UNASSIGNED:<0.001). After adjustment for demographics and clinical covariates, post-PCI myocardial injury was associated with an excess hazard for long-term mortality (hazard ratio, 1.46 [95% CI, 1.20-1.78]). CONCLUSIONS/UNASSIGNED:Myocardial injury defined by elevated CKMB early after PCI is common and associated with all-cause, long-term mortality. More complex coronary anatomy is predictive of post-PCI myocardial injury.

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/UNASSIGNED:Blood transfusion may precipitate adverse outcomes, including heart failure (HF), among patients with acute myocardial infarction (MI). This study characterizes the effects of a restrictive or liberal transfusion strategy on outcomes in patients with MI and anemia with and without baseline HF. METHODS/UNASSIGNED:In the MINT trial (Myocardial Ischemia and Transfusion), 3504 patients with MI and anemia (hemoglobin <10 g/dL) were randomized to a restrictive (hemoglobin <8 g/dL) or liberal (hemoglobin <10 g/dL) transfusion strategy. We compared the effects of transfusion strategy on outcomes among patients with and without baseline HF. The primary outcome was death or HF at 30 days. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:A liberal transfusion strategy is safe for patients with MI and anemia, including those with baseline HF. Restrictive transfusion tended to result in worse outcomes, particularly in patients with baseline HF. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.