Faculty Bibliography

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.

Thrombosis is a major concern in respiratory infections. Our aim was to investigate the magnitude and duration of risk for arterial and venous thrombosis following discharge after respiratory infection. Patients with respiratory infections were identified using the United States Nationwide Readmission Database from 2012 to 2014. Patients admitted with asthma or cellulitis served as comparators. Readmissions for acute myocardial infarction (MI) and venous thromboembolism (VTE) were evaluated at 30 to 180 days. The likelihood of a first thrombotic event after discharge was compared with a 30-day period prior to hospitalization. Among 5,271,068 patients discharged after a respiratory infection, 0.56% and 0.78% were readmitted within 30-days with MI and VTE, respectively. Relative to asthma and cellulitis, respiratory infection was associated with a greater age and sex-adjusted hazard of 30-day readmission for MI (adjusted HR [aHR] 1.48 [95% CI 1.42-1.54] vs. asthma; aHR 1.36 [95% CI 1.31-1.41] vs. cellulitis) and VTE (aHR 1.28 [95% CI 1.24-1.33] vs. asthma; aHR 1.26, [95% CI 1.22-1.30] vs. cellulitis). Risks of MI and VTE attenuated over time. In a crossover-cohort analysis, the odds of MI (OR 1.68 [95% CI 1.62-1.73]) and VTE (OR 3.30 [95% 3.19-3.41]) were higher in the 30 days following discharge after respiratory infection than during the 30-day baseline period. Hospitalization for respiratory infection was associated with increased risks of thrombosis that were highest in the first 30-days after discharge and declined over time.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 6-15% of MI and disproportionately affects women. Scientific statements recommend multi-modality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) to assess mechanisms of MINOCA. Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of MI. If invasive coronary angiography revealed <50% stenosis in all major arteries, multi-vessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and non-ischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intra-plaque cavity or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% of participants undergoing CMR (62/116). A non-ischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome or non-ischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% of the women with multi-modality imaging (98/116), higher than with OCT alone (p<0.001) or CMR alone (p=0.001). An ischemic etiology was identified in 63.8% of women with MINOCA (74/116), a non-ischemic etiology was identified in 20.7% (24/116), and no mechanism was identified in 15.5% (18/116). Conclusions: Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI. Identification of the etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02905357.

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report highlights the findings of the centers, showing how insufficient sleep, sedentariness, and pregnancy-related complications may increase CVD risk in women, as well as presentation and factors associated with myocardial infarction with nonobstructive coronary arteries and heart failure with preserved ejection fraction in women. These projects were augmented by collaborative ancillary studies assessing the relationships between various lifestyle behaviors, including nightly fasting duration, mindfulness, and behavioral and anthropometric risk factors and CVD risk, as well as metabolomic profiling of heart failure with preserved ejection fraction in women. The Go Red for Women Strategically Focused Research Network enhanced the evidence base related to heart disease in women, promoting awareness of the female-specific factors that influence CVD.

Fine particulate air pollution <2.5 μm in diameter (PM_2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM_2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM_2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.