Faculty Bibliography

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

BACKGROUND:Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation. METHODS:Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation. RESULTS:Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia. CONCLUSIONS:Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

Background/UNASSIGNED:The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. Patients with cardiovascular risk factors or established cardiovascular disease are more likely to experience severe or critical COVID-19 illness and myocardial injury is a key extra-pulmonary manifestation. These patients frequently present with ST-elevation on an electrocardiogram (ECG) due to multiple etiologies including obstructive, non-obstructive, and/or angiographically normal coronary arteries. The incidence of ST-elevation myocardial infarction (STEMI) mimics in COVID-19 positive hospitalized patients, and the association with morbidity and mortality is unknown. Understanding the natural history and appropriate management of COVID-19 patients presenting with ST elevation is essential to inform patient management decisions and protect healthcare workers. Methods/UNASSIGNED:The Society for Cardiovascular Angiography and Interventions (SCAI) and The Canadian Association of Interventional Cardiology (CAIC) in conjunction with the American College of Cardiology Interventional Council have collaborated to create a multi-center observational registry, North American COVID-19 ST-Segment Elevation Myocardial Infarction (NACMI). This registry will enroll confirmed COVID-19 patients and persons under investigation (PUI) with new ST-segment elevation or new onset left bundle branch block (LBBB) on the ECG with clinical suspicion of myocardial ischemia. We will compare demographics, clinical findings, outcomes and management of these patients with a historical control group of over 15,000 consecutive STEMI activation patients from the Midwest STEMI Consortium using propensity matching. The primary clinical outcome will be in- hospital major adverse cardiovascular events (MACE) defined as composite of all-cause mortality, stroke, recurrent MI, and repeat unplanned revascularization in COVID-19 confirmed or PUI. Secondary outcomes will include the following: reporting of etiologies of ST Elevation; cardiovascular mortality due to myocardial infarction, cardiac arrest and /or shock; individual components of the primary outcome; composite primary outcome at one year; as well as ECG and angiographic characteristics. Conclusion/UNASSIGNED:The multicenter NACMI registry will collect data regarding ST elevation on ECG in COVID-19 patients to determine the etiology and associated clinical outcomes. The collaboration and speed with which this registry has been created, refined, and promoted serves as a template for future research endeavors.

BACKGROUND:The number of patients treated for aortic valve disease in the United States is increasing rapidly. Transcatheter aortic valve replacement (TAVR) is supplanting surgical aortic valve replacement (SAVR) and medical therapy (MT). The economic implications of these trends are unknown. Therefore, we undertook to determine the costs, inpatient days, and number of admissions associated with treating aortic valve disease with SAVR, TAVR, or MT. METHODS:Using the Nationwide Readmissions Database, we identified patients with aortic valve disease admitted 2012 to 2016 for SAVR, TAVR, and disease symptoms (congestive heart failure, unstable angina, non-ST-elevation myocardial infarction, syncope). Patients not undergoing SAVR or TAVR were classified as receiving MT. Beginning with the index admission, we estimated inpatient costs, days, and admissions over 6 months. RESULTS:<0.01 for all). TAVR index admission costs decreased over time to become similar to SAVR costs by 2016. CONCLUSIONS:Aggregate costs were higher for TAVR than SAVR and were significantly more expensive than MT alone. However, TAVR costs decreased over time while SAVR and MT costs remained unchanged.

Background: Exposure to low-dose ionizing radiation is associated with malignancies. Lead garment specifications in the cardiac catheterization laboratory are not currently regulated, potentially resulting in unprotected areas.
Method(s): Interventional cardiology attendings and fellows wore 7 dosimeters, one externally on the thyroid shield and six inside the lead apron: bilateral axilla, chest wall, and pelvis. Radiation protection included a lower table-mounted lead drape, upper ceiling-mounted lead shield, and use of 7.5 frames per second during fluoroscopy. All procedures were performed with operators standing to the right of the patient. The primary endpoint was operator radiation exposure to the left versus right axilla. Radiation exposures in millirem (mrem) per participant over the study period are shown as median [interquartile range] and compared between left- and right-sided measures using paired Wilcoxon tests.
Result(s): Nine participants (66% female) wore dosimeters during 231 cases. Transradial coronary angiography was selected in 81.1% of cases and PCI was performed in 32.1%. A sterile radiation drape placed on the patient abdomen was used in 18.6% of cases. Median dose area product and fluoroscopy time for the participants ranged from 29.0-60.5 Gy cm² and 6.2-13.5 minutes, respectively. Radiation exposure at the left axilla was higher than the right axilla (5 vs. 0.9 mrem, p=0.018) but did not differ between left or right chest wall and left or right pelvis (Figure).
Conclusion(s): This analysis demonstrates insufficient protection in the left axillary area. The use of additional left axillary protection should be evaluated. (Figure Presented)

BACKGROUND:Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. METHODS:In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. RESULTS:=0.001). CONCLUSIONS:Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT02594111, NCT01709981.

Background Patients with chronic kidney disease (CKD) have poor short-term outcomes after transcatheter aortic valve replacement (TAVR). Methods Retrospective review identified 575 consecutive patients not on hemodialysis (HD) who underwent TAVR at a single center between September 2014 and January 2017. Patients were stratified by pre-procedural glomerular filtration rate (GFR) [>60 (n=297), 30-60 (n=242), and <30 (n=36)]. Outcomes were defined by VARC-2 criteria. Median follow-up was 811 days. Results Transfemoral artery access (TFA), used in 98.8%, and VARC-2 defined procedural success, achieved in 81.4%, did not differ between groups. However, rates of peri-procedural stroke (0.7%, 2.1%, 11.1%; p<0.001) and acute kidney injury (0%, 1.7%, 8.3%; p<0.001) were higher with lower GFR. When compared to GFR >60, risk of all-cause mortality was higher with GFR 30-60 (Hazard ratio (HR) 1.61 [1.00-2.59]) and GFR <30 (HR 2.41 [1.06-5.49]). After adjustment for differences in baseline and procedural characteristics, all-cause mortality remained higher with GFR <60 (adjusted HR 1.67 [1.03-2.70]) compared with GFR >60. Rate of long-term all-cause mortality was higher with lower GFR (10.1%, 16.5%, 19.4%). Kaplan-Meier mortality estimates are shown. Conclusion Few patients with a pre-procedural GFR <30 but not HD undergo TAVR. Despite high use of TFA and no difference in procedural success rate, long-term all-cause mortality after TAVR is higher in patients with pre-procedural CKD. [Figure presented]
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OBJECTIVES/OBJECTIVE:Investigation of novel vertical radiation shield (VRS) in reducing operator radiation exposure. BACKGROUND:Radiation exposure to the operator remains an occupational health hazard in the cardiac catheterization laboratory (CCL). METHODS:A mannequin simulating an operator was placed near a computational phantom, simulating a patient. Measurement of dose equivalent and Air Kerma located the angle with the highest radiation, followed by a common magnification (8 in.) and comparison of horizontal radiation absorbing pads (HRAP) with or without VRS with two different: CCL, phantoms, and dosimeters. Physician exposure was subsequently measured prospectively with or without VRS during clinical procedures. RESULTS:Dose equivalent and Air Kerma to the mannequin was highest at left anterior oblique (LAO)-caudal angle (p < .005). Eight-inch magnification increased mGray by 86.5% and μSv/min by 12.2% compared to 10-in. (p < .005). Moving 40 cm from the access site lowered μSv/min by 30% (p < .005). With LAO-caudal angle and 8-in. magnification, VRS reduced μSv/min by 59%, (p < .005) in one CCL and μSv by 100% (p = .016) in second CCL in addition to HRAP. Prospective study of 177 procedures with HRAP, found VRS lowered μSv by 41.9% (μSv: 15.2 ± 13.4 vs. 26.2 ± 31.4, p = .001) with no difference in mGray. The difference was significant after multivariate adjustment for specified variables (p < .001). CONCLUSIONS:Operator radiation exposure is significantly reduced utilizing a novel VRS, HRAP, and distance from the X-ray tube, and consideration of lower magnification and avoiding LAO-caudal angles to lower radiation for both operator and patient.