Midwest Clinical and Translational Research Meeting of CSCTR and MWAFMR

Bio-engineering1 E-cigarette content alters mitochondrial and biophysical properties of lung endothelium

Mounica Bandela

James Lee

Steven Dudek

The University of Illinois at Chicago

Introduction/Background

Cigarette smoking (CS) is the major cause of Chronic Obstructive Pulmonary Disease (COPD). E-cigarettes are considered by some as a safer alternative; however, inhalation of nicotine-containing e-cigarettes can also cause pathophysiologic changes, and ‘vaping’ of some substances has led to severe lung damage. Our group has previously identified the effect of CS or e-cigarettes in lung endothelial apoptosis and mitochondrial dysfunction.

Objective(s)

This study seeks to characterize the effects of CS or E-cig in lung endothelial dysfunction.

Methods

An important marker of mitochondrial dysfunction is excess mitochondrial ROS (mitoROS), and its production in lung ECs was assessed using MitoSOX reagent. Cytoskeleton rearrangement of ECs upon e-cigarette was assessed by immunofluorescence. Lung EC was exposed to E-cigarette extract (50 µg/ml), resulting in disruption of endothelial permeability assessed by Electric Cell Substrate Impedance (ECIS) and Transwell assay. Atomic Force Microscopy (AFM) was used to probe the biomechanical responses of the manipulated ECs upon e-cigarette challenge.

Results

Blocking mitoROS with Mito-TEMPO (10 µM, 3 h), a cell-permeable antioxidant, decreased mitochondrial superoxide production. We next assessed the role of Mito-TEMPO on E-cigarette-induced endothelial permeability. Pretreatment with Mito-TEMPO provided barrier protection upon e-cigarette challenge. These results suggest a key role of mitoROS in e-cigarette-induced endothelial permeability. E-cigarette exposure induces cytoskeleton rearrangement leading to gap formation in lung EC, as well as alters elastic properties of ECs as measured by AFM.

Conclusion

This study provides novel mitochondrial and biophysical characterization of the effects of e-cigarette exposure on lung EC and advances our understanding of its pathophysiologic effects.

Cardiology/cardiovascular disease2 Procedural outcomes of the use of a mixed reality head mounted display in the cardiac cathterization laboratory

Johnny Chahine1

Stephen George2

Jason Bartos1

Ganesh Raveendran1

Sergey Gurevich1

1University of Minnesota

2Regions Hospital

Introduction/Background

Mixed reality (MR) head-mounted displays (HMDs) have been traditionally deployed as a teaching aid or for reference of patient data, but not for real-time live guidance of procedures.

Objective(s)

To compare the use of MR-HMDs versus standard displays in the cardiac catheterization laboratory.

Methods

There were 294 coronary angiograms (CAs) and right heart catheterizations (RHCs) performed at the University of Minnesota between August 2019 and January 2020 were included in the retrospective observational study. The study was approved by the facility’s Institutional Review Board. The study group (MR-HMD guided) included 62 procedures (33 RHCs, 29 CAs), and the control group (standard display guided) included 232 procedures (164 RHCs, 68 CAs). The study endpoints included procedure time, fluoroscopy time, contrast volume, and procedure-related complications (stroke, myocardial infarction, death, acute kidney injury, or vascular complications).

Results

The mean age was 62.45 years ± 13.5 and 41.5% were female. The median procedure time was significantly lower in the study group (20 minutes (IQR 14–30) vs. 25 minutes (IQR 18–36), p=0.038). There were no significant differences in median fluoroscopy time (1.45 minutes (IQR 0.68–4.93) vs. 1.3 minutes (IQR 0.8–3.1), p=0.84) or median contrast volume used (50 mL (IQR 40–68) vs. 50 mL (IQR 36–67), p=0.87) (figure 1). There was no difference in complications (n=1, 1.6% in the study group vs. n=2, 0.9%, p=0.51).

Abstract 2 Figure 1Abstract 2 Figure 1Abstract 2 Figure 1

Procedural characteristics with the use of a mixed reality head mounted display

Conclusion

The use of MR-HMD in the cardiac catheterization laboratory is safe and may decrease procedure time.

3 Systematic error resulting in a lead reversal epidemic in the emergency room: an underestimated consequence of the global pandemic

Mohammad Al Bataineh

Abdallah Mansour

Mary Dohrmann

University of Missouri Columbia

Introduction/Background

Electrocardiogram (ECG) lead reversal is a well-known phenomenon that can involve limb and precordial leads. It can occur due to a reversal of the lead placement site at the patient level or a reversal of the lead connection at the machine, the latter being less common, but leading to wide-ranging and often subtle ECG changes that are difficult to discover. A series of precordial lead reversals originating from a single machine in the emergency room (ER) resulted in unnecessary evaluation and medical costs.

Objective(s)

The aim of this retrospective evaluation is to highlight a potential systematic error that could affect multiple patients and to highlight the importance of the interpreter’s meticulous assessment of repeated lead reversals in ECGs.

Methods

Over a period of five weeks, multiple ECGs were found to have V1-V2 lead reversal, resulting in errors in interpretation by the computer software for the ECG machine. The ECGs were traced back to a single machine in the ER. A total of 414 ECGs were affected, 44 of which had an interpretation of ‘septal infarct’ by the confirming physician for the ECG. Individual chart review was undertaken of the 44 patients.

Results

Of the 44 charts reviewed, the lead reversal directly resulted in one emergent coronary angiogram and four admissions with extensive cardiac workup (echocardiograms, stress tests, blood tests). Multiple other patients were referred for further outpatient evaluation. Two independent providers deemed the resultant workup clinically inappropriate if the knowledge of the reversal was present at the time of decision-making. Root-cause analysis was carried out, and it was discovered that the leads of the ER machine were switched at the hub during a routine cleaning session. The misplaced leads at their origin from the ECG machine remained undetected for weeks due to a lack of routine technical monitoring since the global pandemic began in March 2020.

Conclusion

The burden of the global pandemic goes beyond direct physical damage caused by the disease. Systematic errors are more common due to staff shortages and shifting priorities. In this series of lead reversals, the shortage of staff to complete scheduled maintenance of equipment resulted in a costly error. Routine technical rounds and meticulous evaluation of repeated lead reversal patterns in ECGs from the same geographical workspace can help identify such errors and reduce the financial burden of health care.

4 Effectiveness of the angiovac system in removal of intravascular masses: a single center experience

Austin Nickell

Phanindra Antharam

Orlin Sergev

Neville Alberto

Dubert Guerrero

University of North Dakota

Introduction/Background

Cardiovascular diseases including endocarditis, deep vein thrombosis, and septic emboli remain highly significant diseases, resulting in numerous hospitalizations and deaths each year. In addition to anticoagulation and thrombolytic therapies that are used for acute and chronic management of these conditions, surgical debridement and thrombectomy can also be performed. Despite the wide prevalence of these techniques, critically ill and hemodynamically unstable patients are often not viable candidates for these procedures owing to the stress placed on the body during sternotomy. An alternative to these invasive procedures is the Angiovac system designed by AngioDynamics in Latham, NY. Performed either percutaneously or open, this minimally invasive technique has been shown as an effective replacement for the removal and filtration of acute thrombi or emboli. This single-centered, retrospective study focuses on patient presenting comorbidities and indications for the procedure as well as post-procedural outcomes.

Objective(s)

To explore the clinical indications, efficacy, and safety of AngioVac for thrombectomy and removal of intravascular masses including vegetations of right sided endocarditis.

Methods

A total of 33 patients who underwent an AngioVac procedure at Sanford Health between March 2014 and October 2019 was reviewed. Data were collected on preexisting comorbidities, indication of procedure, length of hospital stay, and post-operative outcomes.

Results

There were a total of 33 patients (male: 22/33, 67%) with a median age of 47 years (18–82) who underwent an AngioVac procedure at Sanford Health. The most common indications for the procedure were endocarditis (24/33, 73%); intracardiac mass (5/33, 15%); and deep vein thrombosis or pulmonary embolism (2/33, 6%). Post-procedural blood transfusion was required in nearly half (15/33, 45%). Almost all patients (31/33, 94%) required intraoperative vasopressor use. The median length of hospital stay after the procedure was 10 days with interquartile range (IQR) of 18 to 8. Nearly all patients (32/33, 97%) were directed to the ICU following the procedure with an average length of stay of 8 days (IQR = 13–3). The most common complications seen after the procedure were shock requiring vasopressors, (13/33, 39%), pleural effusion (9/33, 27%), and sepsis (4/33, 12%). There was also a single occurrence of 30-day mortality deemed unrelated to the procedure. The success rate seen in the single-centered experience was 85% (28/33).

Conclusion

The AngioVac procedure offered a less invasive option to high risk surgical patients presenting with right sided endocarditis requiring vegetation debulking, intravascular thrombi or cardiac masses.

5 The monsters behind the door: a case of acute heart failure unmasked on patent foramen ovale closure

Pranav Pillai

Apurv Agarwal

Shengnan Zheng

Praneeth Katrapati

Vikas Singh

University of Louisville

Introduction/Background

Fusion of the foramen ovale is usually complete by the age of two years. However, the prevalence of patent foramen ovale (PFO) is reported to be as high as 27.3% in adults based on recent studies, and may lead to certain complications including paradoxical embolism, cryptogenic stroke, and migraine. Here, we present an unusual case of an incidental PFO with right to left shunting in an adult with biventricular thrombi and refractory acute hypoxic respiratory failure.

Objective(s)

Understand how acute heart failure post PFO closure can usually be prevented using RV hemodynamics assessment, and that it could be inevitable despite every measure

Methods

Reviewed electronic medical records to reconstruct the sequence of clinical events. Literature review searching for similar presentations in cases of PFO closure, understanding RV hemodynamics assessment to prevent acute heart failure

Results

A 32-year-old female with cervical carcinoma and history of intravenous (IV) drug use presented with chest pain and dyspnea. Her stay was complicated by increasing oxygen requirements with an elevated D-dimer level. CT chest angiography showed no pulmonary emboli and a transthoracic echocardiogram showed right ventricle (RV) overload with suspicious masses. Subsequent transesophageal echocardiogram demonstrated mobile masses in both ventricles, and a PFO with significant bubbles. In the setting of an elevated D-dimer without bacteremia, the intracardiac masses were consistent with thrombi. Due to worsening respiratory status despite diuresis, a right heart catheterization was performed which showed high pulmonary pressures and normal wedge pressure (table 1). Based on the pulmonary filling pressures and mean arterial pressure (MAP), her calculated pulmonary vascular resistance (PVR): systemic vascular resistance (SVR) was 0.48. Considering refractory respiratory failure due to right to left shunting as the culprit, the PFO was closed to offload the RV (figure 1). However, her respiratory status continued to worsen and progressed to refractory right heart failure. Eventually she had cardiac arrest and succumbed.

Abstract 5 Table 1

Right heart hemodynamics

Abstract 5 Figure 1Abstract 5 Figure 1Abstract 5 Figure 1

Deployed PFO closure device during procedure

Conclusion

PFO closure has applications in several disease processes, notably cryptogenic stroke (as shown in RESPECT, REDUCE, CLOSE and DEFENSE-PFO trials), migraines with aura, decompression sickness, platypnea-orthopnea syndrome and in patients undergoing liver transplantation. This is a rare case of acute right heart failure unmasked by PFO closure. Medications including sildenafil, epoprostenol and nitric oxide are recommended to prevent the increase in RV afterload after PFO closure when the PVR:SVR ratio is > 0.66. In our case, RV offloading was not indicated. Hence, we need to keep in mind that in spite of RV hemodynamics assessment, decompensation may still occur.

6 Piglet cardiopulmonary bypass can simulate intestinal dysbiosis and barrier dysfunction seen with pediatric cardiopulmonary bypass in congenital heart diasease

Jeffrey Salomon1

Jesse Davidson2

Dan Feng1

Ludmila Khailova2

Susan Osorio Lujan2

1University of Nebraska Medical Center

2University of Colorado Denver School of Medicine

Introduction/Background

Congenital heart disease and cardiopulmonary bypass have been implicated in the development of intestinal dysbiosis. Dysbiosis has also been shown to exacerbate inflammation in a variety of disease states. Inflammation is a large contributing factor to the morbidity and mortality following cardiac surgery with cardiopulmonary bypass. As well learn more about the importance of the intestinal microbiome, identifying animal models to reduce the dysbiosis and reduce systemic inflammation after cardiopulmonary bypass is important for this patient population.

Objective(s)

We set out to determine if an existing piglet model of cardiopulmonary bypass could be used to assess changes to the microbiome, intestinal barrier dysfunction, and intestinal metabolites while evaluating markers for systemic inflammation.

Methods

We included seven control piglets with mechanical ventilation (MV) and five piglets with cardiopulmonary bypass and deep hypothermic circulatory arrest (CPB/DHCA). The MV piglets received seven hours of ventilatory support and were then sacrificed. The CPB/DHCA piglets were placed on bypass and then received 75 minutes of DHCA, were warmed, and then supported for four hours off bypass before sacrifice. Blood and stool was obtained in both groups prior to intervention and then at sacrifice.

Results

We noted statistically significant changes in bacterial phyla with increases of Proteobacteria (p< 0.05) and Actinobacteria (p< 0.05), and reductions in healthy Firmicutes (p< 0.05) and Bacteroidetes (p< 0.05) seen in figure 1. There was significant intestinal barrier dysfunction seen with elevations of plasma tight junction proteins claudin-2 (p< 0.0001), and claudin-3 (p< 0.0001), along with intestinal specific cytosolic protein fatty acid binding protein 2 (p< 0.01) seen in figure 2. We noted a trend towards significant reduction in almost all intestinal short chain fatty acids, which regulate inflammation and are cardioprotective, seen in figure 3. There was also a shift of intestinal inflammatory lipid mediators, eicosanoids, in the pre and post stool sample that differed from controls, seen in figure 4. We also showed an increase in IL-1, IL-6, and TNF-a in CPB/DHCA piglets compared to controls, seen in figure 5.

Abstract 6 Figure 1Abstract 6 Figure 1Abstract 6 Figure 1

Bacterial phylum abundance in the intestinal microbiome

Abstract 6 Figure 2Abstract 6 Figure 2Abstract 6 Figure 2

Intestinal barrier dysfunction in CPB versus controls

Abstract 6 Figure 3Abstract 6 Figure 3Abstract 6 Figure 3

Short chain fatty acid levels in CPB versus controls

Abstract 6 Figure 4Abstract 6 Figure 4Abstract 6 Figure 4

Intestinal eicosanoids levels in CPB versus controls

Abstract 6 Figure 5Abstract 6 Figure 5Abstract 6 Figure 5

Systemic cytokine levels in CPB versus controls

Conclusion

These results are very similar to previously published data on the shift of the microbiome in pediatric patients with congenital heart disease as well as demonstrating evidence of intestinal barrier dysfunction and reduction of short chain fatty acids, along with an increase in systemic cytokine levels. This is the first known animal model of cardiopulmonary bypass to evaluate change to the intestinal microbiome and barrier dysfunction. Identifying this model as feasible to study changes to the microbiome will set the stage for future studies evaluating interventions to the microbiome and evaluate systemic inflammation through cytokine profiling and flow cytometry of activate immune cells.

7 Mechanisms of thrombosis in patients with lipoedema and lymphedema

Sharon Shim

Akiirayi Ademoyo

Anu Aggarwal

John Bartholomew

Rohan Bhandari

Robert Burton

Scott Cameron

Matthew Godwin

Suman Guntupalli

Annelise Hamer

Douglas Joseph

Xuefeng Liu

Goeffrey Ouma

Crystal Pascual

Michael Tran

Cleveland Clinic Heart, Vascular and Thoracic Institute

Introduction/Background

Lipoedema, an under-diagnosed disorder almost exclusively affecting women, is caused by an abnormal accumulation of subcutaneous fat in the limbs and is routinely mistaken for lymphedema, which is another cause of limb swelling. Given the recent observation that platelet-specific biomarkers are elevated in both conditions, we hypothesized that platelets may be central mediators in both disorders.

Objective(s)

Capitalizing upon carefully-phenotyped and enriched data, we retrospectively evaluated thrombotic outcomes in patients treated for lipoedema and lymphedema. We then obtained blood from patients with each disorder and investigated platelet-mediated and non-platelet-mediated thrombotic phenotypes ex vivo.

Methods

Data collected over 20 years for patients treated with lymphedema (n=14,958; mean age 66, mean BMI 37.6, 70% female) and a concomitant diagnosis of lipoedema (n=8,493, mean age 71, mean BMI 40.6, 69% female) were evaluated and thrombotic outcomes determined by logistic regression analysis. Washed human platelets were assessed for activation by FACS following exposure to ex vivo to PAR1 agonist (TRAP-6), thromboxane receptor agonist (U46619), P2Y12 receptor agonist (ADP) and GPVI receptor agonist (collagen-related peptide [CRP]). Platelet-deplete plasma was used to determine real-time fibrin and thrombin generation kinetics.

Results

In patients with lymphedema, 19% experienced a thrombotic event over the observational period (14.3% myocardial infarction (MI), 4.0% arterial thrombosis, 0.04% stroke, 0.6% deep vein thrombosis [DVT]). In patients with lipo-lymphedema, 33% experienced a thrombotic event over the observational period (22.2% MI., 8.2% arterial thrombosis, 0.3% stroke, 2.3% DVT, 0.01% pulmonary embolism [PE]). Antiplatelet medications in aggregate analysis conferred no protective effect against thrombosis in lymphedema (OR=1.36[0.41–4.58],p=0.62); however, the P2Y12 receptor antagonist, clopidogrel, conferred protection from PE (OR=0.62[0.43–0.89],p=0.0097). In patients with lipo-lymphedema, the P2Y12 antagonist ticagrelor protected against DVT (OR=0.45[0.21–0.98], p=0.045) and stroke (OR=0.22[0.07–0.72], p=0.012). In patients taking anticoagulants, warfarin conferred no protection from thrombotic events in either lymphedema or lipo-lymphedema, but Factor Xa inhibitors, apixaban and rivaroxaban, protected against stroke in lymphedema and lipo-lymphedema, while apixaban protected against DVT and arterial thrombosis only in lipo-lymphedema. The direct thrombin inhibitor dabigatran protected against DVT only in lymphedema (OR 0.40[0.17–0.94], p=0.035). Platelet reactivity (n=8–12 in each group) with a PAR1 agonist was augmented at concentrations 1–20 μM in both lipoedema and lymphedema vs. control, with a thromboxane receptor against at concentrations 0.1–10 μM in both lipoedema and lymphedema vs. control, with a P2Y12 receptor agonist at concentrations 0.01–10 μM in both lipoedema and especially in lymphedema vs. control, and with a GPVI receptor agonist at 0.05–0.1 μg/mL only in lymphedema vs. control (P< 0.01 in each case). Optical clot density by fibrin generation ex vivo was augmented in lipoedema (median 32924 a.u., p=0.0052)) and lymphedema (median 32207 a.u, p=0.0053) vs. control (25303 a.u.). Thrombin generation was unaltered in either disease (n=19–23 in each group).

Abstract 7 Figure 1Abstract 7 Figure 1Abstract 7 Figure 1

Mechanisms of thrombosis in patients with lipoedema and lymphedema. Platelets are hyperactivated through PAR1 agonist (TRAP6) and thromboxane receptor agonist (U46619) in both lipedema and lymphedema patients. Platelets are hyperactivated with P2Y12 receptor agonist (ADP) and GPVI receptor agonist (CRP) only in lymphedema patients

Abstract 7 Figure 2Abstract 7 Figure 2Abstract 7 Figure 2

Mechanisms of thrombosis in patients with lipoedema and lymphedema. Fibrin generation in platelet-deplete plasma from subjects

Conclusion

Both lymphedema and lipoedema are associated with enhanced platelet reactivity and thrombosis, likely due to the inflammatory nature of these disorders. The clear thrombotic outcomes observed in lymphedema and lipo-lymphedema deserve immediate attention in clinical studies given our data suggesting platelet-mediated and non-platelet-mediated thrombosis. Mechanistic studies are underway to highlight additional interventional targets to abrogate thrombotic risk.

8 Oxalate diet induced chronic kidney disease in dahl-salt-sensitive rats induces uremic cardiomyopathy

Prabhatchandra Dube1

Vaishnavi Aradhyula1

Esha Kashaboina1

Eshita Kashaboina1

Sigdha Gorthi1

Shangari Varatharajan1

Travis Stevens1

Ambika Sood1

Jacob Connolly1

Sophia Soehnlen1

Fatimah Khalaf1

Andrew Kleinhenz1

Oliver Domenig2

Lance Dworkin1

Deepak Malhotra1

Steven Haller1

David Kennedy1

1University of Toledo

2Attoquant Diagnostics

Introduction/Background

Patients with chronic kidney disease (CKD) often develop a ‘uremic’ cardiomyopathy characterized by diastolic dysfunction, left ventricular hypertrophy, and cardiac remodeling, despite contemporary therapies of neurohormonal blockade. This cardiovascular disease is directly responsible for much of the extremely high morbidity and mortality seen in CKD. Development of physiologically relevant animal models of CKD which reflect this cardiovascular pathology is central to mechanistic studies aimed at combatting the cardiovascular disease associated with CKD. Diet induced models of CKD may offer several advantages vs surgical models in terms of clinical relevance and animal welfare. Oxalate is a plant-derived, terminal toxic metabolite that is eliminated through glomerular filtration and renal tubular secretion. Increased dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction and eventually CKD. Dahl-salt-sensitive rats (SS) are a common background strain used to study for hypertensive renal disease however characterization of other diet induced CKD models on this background would allow for comparative studies of CKD associated cardiovascular disease within the same strain.

Objective(s)

Our objective was to identify and characterize a clinically relevant diet-induced rodent model of uremic cardiomyopathy. We hypothesized that SS rats fed a high oxalate diet will develop cardiac injury and dysfunction compared to SS rats fed a normal chow diet, thus serving as a novel rodent model to study the cardiovascular pathophysiology of CKD.

Results

Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks (n=6–8/group). SS-OX rats demonstrated increased 24-hour urinary protein excretion (97% vs SS-NC, p< 0.01) as well as significant elevations of plasma Cystatin C (135% vs SS-NC, p< 0.01). Furthermore, oxalate diet induced hypertension (23% increase in systolic blood pressure vs. SS-NC, p< 0.05) and renin-angiotensin-aldosterone system (RAAS) profile (via LC-MS/MS) demonstrated significant (p< 0.05) increases in circulating plasma angiotensin [1–5] (128% vs SS-NC) and angiotensin I (56% vs SS-NC) as well as suppression of the steroid aldosterone (-54% vs SS-NC). SS-OX also displayed increased cardiac tissue fibrosis (188% vs. SS-NC, p< 0.05) and cardiac inflammation as quantified by morphometric histological analysis (75% vs. SS-NC, p< 0.0001). We also observed an increased cardiac cell cross sectional area in cardiac tissue, indicating pathological cardiac hypertrophy in SS-OX (181% vs. SS-NC, p< 0.0001). Echocardiography of the SS-OX rats further showed an increased posterior wall thickness (128% vs. SS-NC, p< 0.01), increased septal wall thickness (113% vs. SS-NC, p< 0.05), and increased relative wall thickness, indicating left ventricular hypertrophy (124% vs. SS-NC, p< 0.05).

Conclusion

Oxalate diet induces significant RAAS activation and hypertension accompanied by significant cardiac fibrosis, inflammation, left ventricular remodeling and hypertrophy, thus providing a novel diet-induced model to study the cardiovascular complications of CKD.

9 ventricular tachycardia in a normal heart during cardiac stress test: should we watch out for an at(tac)k?

Pranav Pillai

Apurv Agarwal

Shengnan Zheng

University of Louisville

Introduction/Background

Ventricular tachycardia (VT) is an abnormal heart rhythm, characterized by wide QRS complexes (> 120 ms) with three or more consecutive beats at a rate faster than 100 beats per minute (bpm). There are different etiologies involved depending on whether it is sustained (lasts > 30 s, or terminated by an active intervention) or non-sustained (lasts for Here, we would like to present one such rare instance with sustained monomorphic VT induced by exercise in an otherwise healthy patient with no cardiac condition, and explore its clinical implications.

Objective(s)

Understand the clinical significance of sustained monomorphic VT with no structural heart disease (induced by exercise).

Methods

Reviewed electronic medical record to reconstruct the sequence of clinical events. Literature review searching for case reports and abstracts describing similar presentations

Results

A 42-year-old male with history of hypertension, hyperlipidemia and gastroesophageal reflux disease presented with complaints of chest pain and dyspnea for the past two months. He has no significant prior cardiac history. Patient’s symptoms had resolved at the time of evaluation, and was scheduled for a radiotracer exercise stress test with Bruce protocol. At 7 minutes of exercise (stage 3 of Bruce protocol), patient had abrupt onset of sustained monomorphic VT on EKG, with his heart rate reaching 163. He immediately endorsed significant nausea, diaphoresis, and dyspnea. Patient appeared pale and was suddenly hypotensive, down to 68/35 mm Hg. Stress test was terminated and patient was sat down immediately. He converted back to normal sinus rhythm about 10 minutes later, prior to receiving other interventions. A coronary angiogram and transthoracic echocardiogram was performed during the same admission with completely normal results. He was discharged home with outpatient follow-up.

Conclusion

Approximately 33% of individuals without significant cardiac abnormalities exhibit ventricular ectopy during exercise, usually as occasional uniform premature ventricular complexes (PVCs). However, VT is an extremely rare response to exercise especially in a healthy subject, hence the need to rule out coronary ischemia with angiography. The incidence of exercise-induced VT during stress test was 0.08 – 1.1% with 85% of these patients having some form of structural heart disease (most common being coronary artery disease). Although studies exist involving healthy individuals with exercise-induced VT who were followed for years to observe new symptoms or sudden cardiac death, there is not enough data for exercise-induced VT in younger healthy individuals and that may be a potential focus for research in the future.

10 COVID-19 patients on cardiac medication therapy at a higher risk of in-hospital myocardial infarction, cardiac arrest and death

Apurv Agarwal

Hunter Miller

Dipan Karmali

Marianna Weaver

Viral Desai

Hermann Frieboes

Sally Suliman

University of Louisville

Introduction/Background

Existing cardiovascular disease is a known risk factor for poor outcomes in those infected with the SARS-Co-V2 virus. However, despite ongoing studies, there is little data looking at the risks or benefits associated with cardioprotective medications such as aspirin, angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, and statins in COVID-19 patients.

Objective(s)

The primary objective is to identify a relationship between the chronic use of cardioprotective medications (Aspirin, ACEIs, ARBs, beta-blockers, and statins) in those infected with COVID-19 and the development of complications such as myocardial infarction (MI), including STEMI/NSTEMI, cardiac arrest, and in-hospital mortality.

Methods

We performed a single-center retrospective chart review of 503 patients infected with SARS-CoV-2 at the University of Louisville Hospital from March 2020 to February 2021. All patients with a positive polymerase chain reaction test for COVID-19 were included. Medication history was obtained, including aspirin, ACEI/ARBs, beta-blockers, and statins. A chi-square test of independence was used to calculate if the proportion of patients with specific outcomes were independent of the presence or absence of cardiac agents. Risk ratios (RR) were found by unconditional maximum likelihood estimation (Wald). Results were considered significant if p≤0.05.

Results

A total of 503 patients were reviewed with an average age of 50.1 years, 55.9% were Caucasian, and 54.9% were female (figure 1). Among them, 207 (41.1%) were on cardioprotective medications and further analyzed in our treatment group. Within the treatment group, 54.6% were on statins, 48.3% on beta-blockers, 48.3% on ACEIs/ARBs, and 41.6% were on aspirin. Additionally, the majority of patients (59.2%) were on a combination of ≥2 agents, with only 14% on ACEI/ARB in isolation, 10.1% taking just beta-blockers, 8.2% only on aspirin, and 8.2% on statins alone. The overall in-hospital mortality was 9.4% for all patients, and 16.4% for the treatment group. The RR for mortality was highest at 2.6 for statins (p< 0.001, 95% CI: 1.9–3.7), 2.2 for aspirin (p=0.004, 95% CI: 1.4–3.6), 2.1 for beta-blockers (p=0.002, 95% CI: 1.4–3.3), and 2.1 for ACEIs/ARBs (p=0.003, CI: 1.4–3.2). The risk of mortality was also significantly elevated for patients on various drug combinations, as shown in the plot below (figure 2). Of note, older age was independently associated with a higher incidence of mortality (figure 3). The incidence of MI was 6.4% in all patients and 10.1% in the treatment group. Among patients who had MI, 51.3% were on a statin (RR:2.4, p< 0.001, 95% CI: 1.6–3.5). Notably, there was no association between MI and aspirin, beta-blockers, or ACEIs/ARBs. The overall incidence of cardiac arrest was 4.1% and was 6.7% in the treatment group. The highest association was found between cardiac arrest and the use of aspirin with a RR of 2.8 (p=0.005, 95% CI: 1.6–4.9). Similarly the RR for beta-blockers was 2.6, (p=0.004, 95% CI: 1.6–4.3), 2.4 for statins (p=0.004, 95% CI: 1.5–3.8), and 2.3 for ACEIs/ARBs (p=0.016, 95% CI: 1.3–4.0).

Abstract 10 Figure 1Abstract 10 Figure 1Abstract 10 Figure 1

Demographic distribution of study population

Abstract 10 Figure 2Abstract 10 Figure 2Abstract 10 Figure 2

Forest plot demonstrating the risk of mortality for patients on various combinations of medications (Risk Ratio *p<0.05, **p<0.01)

Abstract 10 Figure 3Abstract 10 Figure 3Abstract 10 Figure 3

Plot showing association of increasing age with worse outcomes (p<0.01 for all outcomes)

Conclusion

Our study highlights several key points regarding the chronic use of cardioprotective medications in patients infected with COVID-19. Firstly, chronic use of statins was associated with an increased risk of MI and overall mortality, despite their well-documented anti-inflammatory effects. They were also associated with a high risk of cardiac arrest. In contrast, ACEI/ARBs appear to have the lowest risk of cardiac arrest and death and no association with MI. To our knowledge, this is the first study to compare these agents and their associated risk of developing cardiac complications in those infected with COVID-19 and emphasizes the need for further research.

11 A triad of pericarditis, pericardial effusion< and pleural effusion as the predominant presentation of rheumatoid arthritis

Adam Devine

Michael Aljadah

Rebecca Weiner

Iryna Nemesh

Divyanshu Mohananey

Medical College of Wisconsin

Introduction/Background

Herein, we describe a case of a 67-year-old African American male who presented to the emergency department (ED) with a sharp, pleuritic chest pain and shortness of breath. After several admissions and extensive work up, he was ultimately diagnosed with a persistent pleural effusion, pericardial effusion, and secondary constrictive pericarditis due to Rheumatoid Arthritis (RA). We believe this is the first manuscript that demonstrates this triad of cardiopulmonary manifestations as a predominant presentation of RA in a patient with a prior diagnosis of non-erosive, seropositive RA lacking typical musculoskeletal features. By highlighting immunological disorders such as RA in the differential diagnosis, in the setting of a refractory pericardial effusion and serositis, this case report will address key aspects of the presentation both in the emergency and inpatient settings, review the criteria for a RA diagnosis, and emphasize areas of importance in predominantly cardiopulmonary extra-articular manifestations of a typically musculoskeletal disease.

Objective(s)

A 67-year-old man with a significant past medical history for seropositive, non-erosive rheumatoid arthritis (RA), chronic obstructive pulmonary disease, paroxysmal atrial fibrillation, chronic kidney disease (CKD) stage 1, gastroesophageal reflux disease (GERD), esophageal dysmotility, and peptic ulcer disease (PUD) who presented to the ED with sharp, pleuritic chest pain and shortness of breath.

On his first admission, the evaluation for his first episode of chest pain revealed nonspecific ST-T wave changes on 12-lead electrocardiogram (ECG) and nondiagnostic elevations in high sensitivity troponin levels, which were attributed to poor renal clearance from his CKD. An initial transthoracic echocardiogram (TTE) was performed in the ED and was unremarkable. With a history of GERD, antacids were administered with partial improvement of his chest pain. Given the presenting history, unremarkable TTE, and cardiac biomarkers and ECG non-suggestive of ischemia, his chest pain was defined as non-cardiac. Further gastroesophageal workup revealed the etiology of his symptoms, as esophagram displayed esophageal dysmotility, intra-esophageal reflux, and poor clearance on marshmallow challenge. Patient was discharged with conservative GERD management.

He was admitted for the second time three days later for evaluation and management of persistent, sharp pleuritic chest pain, worsened when lying supine, and improved with leaning forward. He denied any recent trauma, cardiothoracic surgeries, radiation exposure, or myocardial infarctions. On examination, he was afebrile and without audible friction rub. ECG showed diffuse ST-elevations in anterior and inferior leads and PR depressions in leads II, III, AVF, V5, and V6, with concern for pericarditis (figure 1a). High-sensitivity troponin levels were elevated, but stable from previous admission. Posterior-anterior (PA) chest x-ray showed a small left sided pleural effusion (figure 2a). Repeat TTE depicted a new small, circumferential pericardial effusion measuring up to 7 mm in depth, without any echocardiographic indications of cardiac tamponade, and normal cardiac function. There was also a 20% respiratory phasic variation in the mitral valve inflow velocity (<25% considered normal). The pericardial effusion was further described on CT Angiogram of the chest with contrast (figure 2b, c). With pericarditis suspected, a detailed work up for the causes of pericarditis was pursued.

Rheumatological origins were then considered, as the c-reactive protein (CRP) was elevated at 7.4 mg/dL and erythrocyte sedimentation rate (ESR) was elevated at 78 mm/hr. There was low suspicion for infectious etiology as he was without leukocytosis and his blood, urine, and sputum cultures returned negative. Uremic pericarditis was ruled out with blood urea nitrogen (BUN) within normal limits. Medical record review revealed a positive rheumatoid factor (RF) of 356 IU/mL and an elevated anti-cyclic citrullinated peptide (CCP) antibody IgG/IgA >250 IU/mL years ago, which was drawn for workup of large joint polyarthralgias. At that time, his physical exam was unremarkable for inflammatory joint deformities, synovitis, or joint effusions. Furthermore, radiographic pursuits revealed no bony erosions or rheumatoid changes. Without clinical correlation of positive high titer RF and CCP antibodies, he did not meet diagnostic criteria for RA, and there was no indication for initiation of medical therapies. Rheumatology recommended close follow-up for monitoring, but patient elected to discontinue care due to lack of development of typical RA symptoms.

During this second admission, the patient continued to show neither synovitis nor evidence of inflammatory arthritis on physical exam or repeat imaging. He was treated idiopathically with high dose aspirin and colchicine for pericarditis. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are recommended in combination therapy for idiopathic pericarditis, were avoided due to patient’s history of PUD. Notwithstanding, the clinical signs of pericarditis, a pleural effusion, and a pericardial effusion, there remained concern of an underlying rheumatological disease, as the aforementioned cardiopulmonary and infectious workup was unrevealing thus far. As the patient was medically stable on aspirin and colchicine, his predischarge plan included continuing medical management for a four-week period.

In spite of outpatient treatment with colchicine and aspirin, the patient was admitted for a third time five days later for relapsing persistent sharp, pleuritic chest pain and unresolving shortness of breath. ECG showed persistent, diffuse ST-elevations in anterior and inferior leads, with resolving PR depressions in leads II, III, AVF, and V6. Patient was also noted to be in atrial fibrillation with rapid ventricular response (figure 1b). TTE revealed small to moderate circumferential stable pericardial effusion, unchanged from prior study, but now notable for a rise in respiratory phasic variation in mitral valve inflow velocity to 35%, suggesting clinical correlation of constrictive pericarditis. The PA chest x-ray showed progression of the left sided pleural effusion (figure 2). A cardiac MRI demonstrated a clear demarcated circumferential rim of delayed enhancement in the pericardium consistent with pericarditis and free breathing sequences showing respirophasic septal shift (figure 2), consistent with constrictive pericarditis.

Based on prior elevation of RF and CCP antibodies, now in the setting of constrictive pericarditis and poly-serositis, refractory to aspirin and colchicine, with elevated CRP and ESR, the impression of inpatient rheumatology team was that the patient’s pericarditis was secondary to new diagnosis of RA. There was no indication to repeat RF or CCP serologies, given his history of highly RA specific, positive high-titers. The patient was then started on prednisone 40 mg daily, in addition to aspirin and colchicine. After only two days, the patient reported significant improvement in symptoms. With clinical improvement on prednisone and a formal diagnosis of RA, pericardiocentesis or pericardiotomy were indicated for consideration in treatment of constrictive pericarditis, but ultimately not pursued.

Unfortunately, the patient was admittedly non-adherent to the prescribed regimen and would again present to the ED with acute hypoxic respiratory failure. On initial evaluation he was afebrile, but now requiring 4L of supplemental oxygen. Arterial Blood Gas would show oxygen saturation of 89.1%, pH of 7.40, PaCO2 of 33 mmHg, and HCO3- of 20. ECG would show no ST-elevations or PR-depressions (figure 1c). CT Angiogram would show significant progression of the known left pleural effusion, with new development of potential areas of loculation and near-complete collapse of the left lower lobe. There was no evidence of interstitial lung disease. Based on these findings, infectious etiologies were thoroughly explored, yet workup with blood, urine, and sputum cultures were negative. Nucleic Acid Amplification Tests (NAAT) for Chlamydia pneumoniae, Legionella pneumoniae, and Mycoplasma pneumoniae were negative. Streptococcus pneumoniae antigen and viral respiratory panel were negative as well. Procalcitonin was within normal limits. A diagnostic and therapeutic thoracentesis with chest tube placement was then pursued, which would remove 1.4L. The pleural exudate would show 10,200 unit/liter WBC (ref: <1000 unit/liter), a LDH of 600 unit/L (ref: <50% serum concentration), glucose of 257 mg/dL (ref: 40–70 mg/dL), pH of 8.0 (ref: 7.6–7.64), and protein of 4.4 g/dL (ref: 1–2 g/dL). His serum total protein was 7.7 g/dL and LDH 2047 unit/L. The exudative effusion would be classified most probably secondary to RA. With infectious rule out, prednisone was restarted, and he would be continued an indefinite course of steroid therapy, with eventual transition to azathioprine, a steroid-sparing agent, in the future.

Methods

RA is a systemic inflammat

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