Faculty Bibliography

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.

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: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.

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.

Cardiogenic shock (CS) is critical end-organ hypoperfusion attributable to reduced cardiac output. Acute ST-segment-elevation myocardial infarction with CS (AMI-CS) has high mortality. Clinical research is challenging in such patients as they often cannot provide consent, lack available legal representatives, and require initiation of therapy. Multiple trials have enrolled patients with AMI-CS outside the United States under deferred consent. Trials in the United States have enrolled patients with out-of-hospital cardiac arrest under exception from informed consent (EFIC). However, AMI-CS has a longer therapeutic window to initiate treatment than out-of-hospital cardiac arrest, and more patients or their representatives can engage in treatment decisions. We provide a rationale for how a trial enrolling patients with AMI-CS could qualify for conduct using EFIC by meeting each criterion specified in US human subject regulations. AMI-CS is a life-threatening situation, available treatments are unsatisfactory, and collection of valid evidence is necessary. Obtaining informed consent is often not feasible, and trial participation could benefit subjects. Only enrolling consented patients is impracticable and could reduce the study's generalizability. We propose a therapeutic window of 30 minutes within the study intervention must be initiated, with consent sought within 15 minutes, respecting any refusal or objection to enrollment, and otherwise enrollment under EFIC. A trial could enroll patients with AMI-CS under EFIC and can involve both patients and their representatives. Successful use of EFIC in trials of other interventions in patients with CS or enrolling patients with other acute cardiovascular conditions could increase the available evidence base to improve care.

BACKGROUND:In the COMPLETE (Complete vs Culprit-Only Revascularization to Treat Multi-Vessel Disease After Early PCI for STEMI) trial, complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) reduced important outcomes compared with culprit-only percutaneous coronary intervention. Whether clinical outcomes in STEMI patients with MVD are influenced by the presence of a left anterior descending (LAD) nonculprit lesion (NCL) remains unknown. OBJECTIVES/OBJECTIVE:This study sought to compare: 1) cardiovascular outcomes among patients with an NCL in the proximal/mid-LAD to patients with an NCL in other locations; and 2) the benefit of NCL revascularization in patients with and without a proximal/mid-LAD NCL. METHODS:The COMPLETE trial enrolled patients presenting with STEMI and MVD to angiography-guided complete revascularization vs a culprit lesion-only strategy. All coronary angiograms were evaluated in a central core laboratory. In this prespecified subanalysis, treatment effect according to proximal/mid-NCL location was determined for the coprimary outcomes of: 1) cardiovascular death or new myocardial infarction; and 2) cardiovascular death, new myocardial infarction, or ischemia-driven revascularization. Cox proportional hazards models were performed with an interaction term for treatment allocation and NCL location. RESULTS:Of the 4,041 subjects in COMPLETE, 1,666 patients had a proximal/mid-LAD NCL (41.2%). The first coprimary outcome occurred in 8.5% (2.9%/y) of patients with a proximal/mid-LAD NCL vs 9.9% (3.4%/y) in those without (adjusted HR: 0.83; 95% CI: 0.67-1.03). Complete revascularization had a similar benefit in reducing the first coprimary outcome for patients with a proximal/mid-LAD NCL (7.7% vs 9.2%; HR: 0.85; 95% CI: 0.61-1.18) and those without (8.0% vs 11.9%; HR: 0.65; 95% CI: 0.50-0.86), with no differential treatment effect (interaction P = 0.235) CONCLUSIONS: Among patients presenting with STEMI and multivessel CAD, those with a proximal/mid-LAD NCL had similar event rates to those without. The benefit of complete revascularization between the groups was similar, with no evidence of heterogeneity.