Faculty Bibliography

OBJECTIVES/OBJECTIVE:This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA). BACKGROUND:Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization. METHODS:Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as ≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of ≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed. RESULTS:In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease ≥50%, 92.2% with at least single-vessel CAD and no LM disease ≥50%, and only 4.9% without anatomically significant CAD. Results using a ≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance. CONCLUSIONS:CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

Women are under-represented as leaders of cardiovascular randomized controlled trials, representing 1 in 10 lead authors of cardiovascular trials published in high-impact journals. Although the proportion of cardiovascular specialists who are women has increased in recent years, the proportion of cardiovascular clinical trialists who are women has not. This gap, underpinned by systemic sexism, has not been adequately addressed. The benefits of diverse randomized controlled trial leadership extend to patients and professionals. In this position statement, we present strategies adopted by some organizations to end gender inequality in research leadership. We offer an actionable roadmap for early-career researchers, scientists, academic institutions, professional societies, trial sponsors, and journals to follow, with the goal of harnessing the strength of women and under-represented groups as research leaders and facilitating a just culture in the cardiovascular clinical trial enterprise.

BACKGROUND:A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19. METHODS AND RESULTS/RESULTS:Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53-169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61-3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76-2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37-3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11-3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes. CONCLUSIONS:Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.

Guideline-based medical therapy is the foundation of treatment for individuals with coronary artery disease. However, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting may be beneficial in patients with acute coronary syndromes, refractory symptoms, or in other specific scenarios (eg, left main disease and heart failure). While the goal of percutaneous coronary intervention and coronary artery bypass grafting is to achieve complete revascularization, anatomical and ischemic definitions of complete revascularization and their methodology for assessment remain highly variable. Such lack of consensus invariably contributes to the absence of standardized approaches for invasive treatment of coronary artery disease. Herein, we propose a novel, comprehensive, yet pragmatic algorithm with both anatomical and ischemic parameters that aims to provide a systematic method to assess complete revascularization after percutaneous coronary intervention or coronary artery bypass grafting in both clinical practice and clinical trials.

OBJECTIVE:<0.05, |log2foldchange| >0.5) and analyzed using weighted gene co-expression network analysis. Weighted gene co-expression network analysis revealed blood modules enriched for immune activation, secretory granules, and coagulation in patients with PAD. Of these 127 differentially expressed transcripts, 40 were significantly associated with MACLE (log-rank false discovery rate <0.1). MicroRNA-4477b was significantly increased in patients with PAD with subsequent MACLE and in a mouse hindlimb ischemia model. CONCLUSIONS:A whole blood transcript signature identified patients with symptomatic PAD and PAD patients at increased risk of MACLE. A previously uncharacterized transcript microRNA-4477b was overexpressed in prevalent PAD, incident MACLE, and in a mouse hindlimb ischemia model. Our novel transcriptomic signature provides insight into potential mechanisms of patients with severe symptomatic PAD.

Background: In ISCHEMIA, an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality compared with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular endpoints was myocardial infarction. Methods: ISCHEMIA prespecified that the primary and major secondary composite endpoints of the trial be analyzed using two MI definitions. For procedural MI, the primary MI definition used CK-MB as the preferred biomarker whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times URL for PCI and >10 times for CABG. Procedural MI definitions included (i) a category of elevated biomarker only events with much higher biomarker thresholds (ii) new ST segment depression of ≥ 1mm for the primary and ≥ 0.5 mm for the secondary definition and (iii) new coronary dissections ≥ NHLBI grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. Results: Procedural MI's accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive vs conservative strategy using the primary [2.7% vs. 1.1%; adjusted HR 2.98 (95% CI 1.87, 4.73)] and secondary [8.2% vs. 2.0%; adjusted HR 5.04 (95% CI 3.64, 6.97)] MI definitions. Type 1 MI's were less frequent with the invasive vs conservative strategy using the primary [3.40% vs. 6.89%; adjusted HR 0.53 (95% CI 0.41,0.69); p<0.0001], and secondary [3.48% vs 6.89%; adjusted HR 0.53 (95% CI 0.41, 0.69); p<0.0001] definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI compared to no MI using the primary [adjusted HR 3.38 (95% CI 2.03,5.61); p<0.001] or secondary MI definition [adjusted HR 3.52 (2.11, 5.88); p<0.001]. Conclusions: In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and using the secondary MI definition. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01471522.