bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17113: Secondary Infections Are Common in Patients Hospitalized for COVID-19 and Are Associated With Severe Outcomes
Authors: Anderson Elizabeth R , Azam Tariq , Shadid Husam , Pan Michael , Berlin Hanna , Meloche Chelsea , Feroze Rafey , Leya Jeff , O'Hayer Patrick , Kaakati Rayan , bitar abbas , Padalia Kishan , Perry Daniel , Blakely Pennelope , Zhao Peiyao , Zhao Lili , Hayek Salim
Published: November 2020

Background:
Secondary infections occur in 10-15% of critically ill sepsis patients. Anecdotal reports suggest secondary infections are common in coronavirus disease 2019 (COVID-19), however data are lacking. We examine the rate of secondary infections in hospitalized patients with COVID-19 and its impact on the cytokine surge and in-hospital outcomes.

Methods:
The Michigan Medicine Covid-19 Cohort (M2C2) is an ongoing prospective observational study in which detailed clinical, laboratory and outcome data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without respiratory symptoms were not included in this cohort. We define secondary infections as physician-diagnosed and treated bacterial or viral infections secondary to SARS-CoV-2.

Results:
Of 553 COVID-19 patients hospitalized at Michigan Medicine, 191 (34.5%) developed a secondary infection during hospitalization. The mean age of patients with a secondary infection was 60 years, 61.3% were male compared to 58.8 years, 53.5% male in patients with no secondary infection. Bacterial pneumonia, including ventilator-associated pneumonia, was the most prevalent secondary infection among hospitalized patients (78.5%). Other secondary infections included urosepsis (14.1%), bacteremia (16.8%), and 17.3% of patients developed other types of infections such as shingles and clostridium difficile. 25.8% of patients without secondary infections received antibiotics during their admission compared to 47.1% of patients with secondary infections. Multiple secondary infections (>1) occurred in 43 (8.2%) of patients. Patients with secondary infections were more likely to develop acute kidney injury (78.0% vs. 38.3%, p<0.0001), acute respiratory distress syndrome (78.0% vs. 22.3%, p<0.0001), and death (26.2% vs. 10.2%, p<0.0001) during their hospitalization compared to patients without secondary infections.

Conclusions:
Secondary infections are common in hospitalized patients with COVID-19 and are associated with life-threatening complications and high mortality. This study suggests that secondary infection prevention may be especially important in COVID-19 patients.
Abstract 17116: Incidence and Costs of Major Atherothrombotic Vascular Events Among Patients With Peripheral Artery Disease After Revascularization
Authors: Bonaca Marc P , Hess Connie N , Kharat Akshay , Desai Urvi , Milentijevic Dejan , Laliberté François , Zuckerman Peter R , Benson John , Lefebvre Patrick , hiatt william R
Published: November 2020

Introduction:
Peripheral artery disease (PAD), frequently requiring lower-extremity revascularization (LER), is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major amputation of vascular etiology, myocardial infarction [MI], ischemic stroke [IS], cardiovascular [CV] death). Understanding the incidence and healthcare costs of such events in PAD patients post-revascularization may be important in translation.

Methods:
Patients with PAD who underwent LER were identified from Optum Clinformatics Data Mart claims database (Q1 2014 - Q2 2019). The first LER was considered index. Patients were required to be ≥50 years old at index with ≥6 months of prior health plan enrollment. Patients with IS, atrial fibrillation (AF), venous thromboembolism (VTE), intracranial hemorrhage, ESRD, or oral anticoagulant (OAC) use pre-index; or diagnoses of MI 30 days or ALI 14 days pre-index were excluded. Patients were followed until the earliest of 1) end of enrollment/data; 2) diagnosis of AF or VTE; or 3) OAC use. For each major vascular event, the incidence rate was assessed as the number of first events divided by patient-years of observation. Event-related healthcare costs per-patient-year (PPY) were also reported.

Results:
Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event over a median follow-up of 1.0 years (IQR: 0.4-2.1). The composite event incidence rate was 13.81 per 100 patient years [ALI: 5.51; lower-limb amputation: 5.15; MI: 3.19; IS: 2.06; CV-related death: 0.88]. PPY event-related costs ranged from $57,825 for IS to $108,302 for lower-limb amputation (Figure).

Conclusions:
One in six PAD patients have a major atherothrombotic vascular event within one year post-LER. Costs of these events are high, particularly for limb complications. Therefore, reducing the rate of such events could reduce the overall healthcare costs for this population.
Abstract 17120: Association of Endotoxemia and Endothelin-1 With Development of Cardiac Allograft Vasculopathy After Heart Transplantation
Authors: Braghieri Lorenzo , Bohn Bruno , Mondellini Giulio , Javaid Azka , Kim Andrea J , Onat Hatice D , Latif Farhana , Farr Maryjane , Sayer Gabriel T , Uriel Nir , Takeda Koji , Naka Yoshifumi , Demmer Ryan , Colombo Paolo C , Yuzefpolskaya Melana
Published: November 2020

Introduction:
Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplant (HT). Inflammation is a known cardiovascular risk factor, with gut derived endotoxemia potentially instigating this process, leading to endothelial damage. Our prior work showed that elevation of biomarkers of inflammation (endothelin-1 (ET-1)) and endotoxemia (lipopolysaccharide (LPS)) persists after HT. We investigated the association of LPS and ET-1 with subsequent development of CAV.

Methods:
Pts who met the following criteria were included: i) blood sampling ≥6 mo post-HT; ii) no evidence of CAV at the time of sampling. Pts were followed up to 2.3y after sampling. Cox-PH was used to regress freedom from CAV on LPS and ET-1 (≤ vs >median), time from HT to sampling (≤ vs >1y), interaction among variables.

Results:
33 HT pts enrolled, mean age 57±11y; 70% male; median time post-HT 1.96(0.5-3.7)y. 17(52%) pts developed CAV at 0.7(0.6-1)y following blood collection. Baseline characteristics of pts who developed CAV vs not were similar, except for longer median time post-HT in pts who developed CAV: 2.4(0.7-5.3) vs 1.05(0.5-2.7)y, p=0.1. Median LPS and ET-1 for the entire cohort were 0.34(0.28-0.45) EU/ml and 1.83(1.26-2.72) pg/ml. Pts with >median LPS or ET-1 values trended towards higher risk of developing CAV: HR 1.79(0.66, 4.85), p=0.3 (
Fig.1A
); HR 2.05(0.71, 5.92), p=0.2 (
Fig.1B
). No association was observed between time post-HT and CAV: HR=0.87 comparing ≤ vs. >1y, p=0.8. Pts with both >median LPS and ET-1 levels (n=7) were at significantly higher risk of CAV: HR 2.96(1.06, 8.27), p=0.039, compared to others (
Fig.1C
). When examining pts sampled within the first year of HT (N=14), pts with >median LPS (N=5) were at particularly increased risk of CAV: HR 9.71(0.97, 96.9), p=0.05, while pts with >median ET-1 were not.

Conclusions:
Elevated LPS and ET-1 synergistically associate with increased CAV risk post-HT. Further studies are warranted to validate these findings.
Abstract 17128: Sleep Irregularity is Associated With Increased All-Cause Mortality
Authors: Katamreddy Adarsh , Uppal Dipan , Ramani Gokul , Rios Saul , Miles Jeremy , Wang Yu Chiang , Faillace Robert
Published: November 2020

Introduction:
Circadian rhythm disruptions are associated with increased cardiovascular disease risk. We aim to investigate if day-to-day variation in sleep duration and onset of sleep are associated with cardiovascular and all-cause mortality.

Methods:
388 subjects with sleep data from Midlife in the United States(MIDUS) 2 Biomarker study(2004-09) were included. Objective sleep data was measured using the Actiwatch® device. Sleep onset, duration, sleep-wake cycles were collected for 7 consecutive days. Mean and standard deviations in sleep duration and time of onset of sleep over 7 days were calculated to assess for sleep irregularity and tertiles created. Mortality data was available with a follow up until December 2016. Cox proportional regression analysis was performed. Competing risk analysis for cardiovascular mortality was done with fine and gray subdistribution hazard.

Results:
Mean age 54.56±11.79 years; females 230(59.3%). BMI 30.56±7.06 kg/m
2.
Over a median of 8.6 years follow up, 37 patients died including 10 deaths due to cardiovascular mortality. Sleep duration SD tertiles ranges were: 11-41 minutes, 42-67 minutes and 68-257 minutes in lowest to highest tertiles respectively. There was no statistically significant increase in cardiovascular mortality with variation in sleep duration. Tertile 3 vs 1: HR 4.00(0.45-35.48,p 0.21), but there was statically significant increase in all-cause mortality tertile 2vs1 and 3vs1 -HR 3.63(1.19-10.99, p 0.02), HR 3.99(1.33-11.94, p 0.01) respectively. Fully adjusted model showed tertile 2vs1 and 3vs1 HR 3.51(1.12-10.99, p 0.03), HR 4.85(1.52-15.49, P < 0.01) respectively.

Conclusions:
Day to day variation in sleep duration is associated with increased all-cause mortality but not cardiovascular mortality after adjusting for mean sleep duration, inflammation, diabetes, age, BMI, renal function and blood pressure.
Abstract 17130: Systemic Infection From Non-Pocket Source is Associated With Worse Outcomes Compared With Pocket Source
Authors: KHAN MUHAMMAD ZUBAIR , Khine Kay , Saltzman Heath , Kutalek Steven P , Gupta Ashwani
Published: November 2020

Introduction:
Systemic infection can occur in patients with cardiac devices due to spread from pocket infection or a non-pocket source. Data comparing outcomes of systemic infection from pocket vs. non-pocket source are lacking

Hypothesis:
We hypothesized that systemic infection from non-pocket source is associated with worse outcomes compared with pocket source.

Methods:
We collected data for all patients with systemic infection, who underwent transvenous lead extraction (TLE) between April 2004 and June 2015. Patients were divided into 2 groups- systemic infection from pocket source and non-pocket source.

Results:
Out of total 700 TLE procedures for infectious indication, 407 patients (58.1%) had evidence of systemic infection. Out of these, 167 (41%) had systemic infection from pocket source and 240 (59%) had systemic infection from non-pocket sources. Patients with pocket source were older (69.7± 13.4 vs. 66.3± 13.5 years, p value 0.011), less likely to be on dialysis (8.4% vs. 23.8%), and more likely to have CRT system (39.5% vs. 23.8%). Pocket source group had higher incidence of coagulase negative staphylococcus infection (32.3% vs. 19.6%) and presence of abandoned leads (32.3% vs. 10.8%).Patients with non-pocket source were more likely to have endocarditis (81.7% vs. 55.1%). There was no difference in TLE procedure outcomes, complications during hospital stay, and 30-day mortality (10.3% vs. 13.7%, p value 0.330). However, 1-year mortality was significantly higher in patients with non-pocket source (41% vs. 28.1%, p value 0.019). Kaplan-Meier survival curves showed worse survival in non-pocket source group up to 6 years of follow up.

Conclusions:
In conclusion, there is no difference in procedural or short-term outcomes between patients with systemic infection from pocket vs. non-pocket source after TLE. However, patients with systemic infection from non-pocket source are more likely to have endocarditis and have worse long-term mortality.
Abstract 17134: Biomarker-Based Risk Prediction of Incident Heart Failure Over 5 Years in Prediabetes and Diabetes: Pooled Analysis Across 3 US Community Cohorts
Authors: Vaduganathan Muthiah , Pandey Ambarish , Patel Kershaw , Ayers Colby , Ballantyne Christie M , Kosiborod Mikhail N , Carnethon Mercedes R , DEFILIPPI Christopher , McGuire Darren K , Khan Sadiya , Caughey Melissa , De Lemos James A , Everett Brendan M
Published: November 2020

Introduction:
While patients with dysglycemia and known CV disease face high risks of transition to HF and benefit from risk reduction strategies (such as SGLT-2 inhibitors), identification of at-risk patients without CV disease for allocation of primary prevention interventions is less clear. Biomarkers may improve risk stratification and inform targeted application of preventive strategies.

Methods:
Participants free of CV disease from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were included. A biomarker score was developed incorporating hs-cTnT ≥ 6 ng/L, NT-proBNP ≥ 100 pg/mL, hs-CRP ≥ 3 mg/L, and LVH by electrocardiogram. Among participants with dysglycemia, 5-year risks of incident HF and the number of HF events potentially prevented per 1,000 participants treated with an SGLT-2 inhibitor for 5-years were estimated.

Results:
Among 6,799 participants with prediabetes (66.8%) and diabetes (33.3%), there were 891 incident HF events over median follow-up of 17 years. The biomarker score alone demonstrated good discrimination and calibration for predicting 5-year HF risk [C-statistic 0.76 (0.71 to 0.81), calibration p value = 0.62]. Among those with dysglycemia, 5-year risk of HF in the very low (score = 0) and low biomarker score groups (score = 1) were similar to that observed among individuals with euglycemia (0.74%). The 5-year risk of HF increased in a graded fashion across increasing biomarker score groups. For every 1,000 participants with diabetes treated with an SGLT-2 inhibitor for 5-years, the estimated number of HF events prevented was estimated to be 4, 5, 14, and 41, respectively for individuals with scores of 0, 1, 2, and 3-4.

Conclusions:
Among adults with prediabetes and diabetes, a biomarker score can inform HF risk stratification. Individuals with diabetes and high biomarker scores face the highest risk of HF and are expected to benefit the most from SGLT-2 inhibitors.
Abstract 17137: Risk Factors for New-onset Aortic Stenosis and Aortic Valve Replacement in End-Stage Renal Disease Patients - Results From the Swedish Renal Registry
Authors: Vavilis Georgios , Back Magnus , Barany Peter , Szummer Karolina
Published: November 2020

Introduction:
Risk of aortic valve calcification increases in CKD. The incidence and the risk of new-onset AS among dialysis patients (DP) remains unknown.

Objectives:
We aimed to evaluate the IR and predictors of AS and AVR in DP.

Methods:
All DP (n= 14,054) in the national Swedish Renal Registry between 1993-2018, with no prior AS or AVR, were included. AS was defined by ICD-10 codes or surgical procedure codes.

Results:
During a median follow-up time of 2.8 years (IQR 1.1-5.7), 596 (4.2%) DP were diagnosed with AS; IR of 15/1000 (95% CI: 13-16/1000) p-y (Figure 1a). AVR was done in 113 (0.8%) patients; IR 2/1000 p-y (95% CI:2-3/1000) Figure 1b. DP with new-onset AS were older (70.4±11 vs 64.8±15.3, p<0.001), males (76% vs 66%, p<0.001), had AF (19% vs 15%, p=0.010), hypertension (97 % vs 95%, p=0.033) and CAD ((23.3% vs 19%, p=0.008). There was no difference in the risk for AS between hemo-or peritoneal dialysis (HR 1.1, 95%CI: 0.64-1.15 p=0.32). In adjusted Cox models, only male gender (HR 1.44, 95 CI 1.18- 1.76) and AF (HR 1.34, CI 1.07 - 1.67) were associated with new-onset AS. Patients undergoing AVR were comparable in age with the entire cohort (64 ±10 vs 65±15, p=0.51), but had less often HF (7.1% vs 13.6%, p=0.041) and PAD (3.5% vs 11.2%, p=0.011) (Table 1). In adjusted Cox models, only male gender (HR 1.97, 95%CI: 1.12 - 3.46) was associated with AVR.

Conclusions:
Both new-onset AS diagnosis and AVR in DP is associated with male gender.

Kaplan-Meier curves with overall cumulative incidence of:Figure 1a. New onset AS in DP. Log-rank (p<0.0000) test.

Figure 1b. Of AVR. Log-rank (p<0.000) test. Both outcomes were censored at time of death or renal transplantation
Abstract 17143: Acute Coronary Syndromes Associated With SARS-CoV-2 Infection Admissions in a Medium Size Community Hospital
Authors: STAN ANDREEA-CONSTANTA , Durdevic Momcilo , Florante Rosario , Artashesyan Arshavir , Elenius Henrik , Hasan Amrah
Published: November 2020

Background:
The presence of cardiovascular complications were reported in small studies of critical care patients admitted with SARS-CoV-2infection There is a dearth of data regarding presence of acute coronary syndromes (ACS) in patients admitted with symptomatic SARS-CoV-2 infection, the cause of the myocardial injury and particularities of management.

Objectives:
The aim of the study is to describe the presence and type ACS in patients admitted with symptomatic SARS-CoV-2 infection. Secondary outcomes were contributing factors, presenting symptoms and medical management.

Methods:
A descriptive, retrospective study of patients with a positive COVID-19 test and symptomatic infection admitted from 10 March 2020 to 10 April 2020 in our hospital.

Results:
There were a total of 127 patients admitted with symptomatic SARS-CoV-2 infection. The most common ACS was Type II Myocardial Infarction (MI). 16 patients were diagnosed with type II MI, 3 patients with Non ST elevation myocardial infarction (NSTEMI) and no patient was diagnosed with unstable angina and ST elevation myocardial infarction (STEMI). The most common cause of Type II MI was hypoxia followed by congestive heart failure and new onset atrial fibrillation. One patient has chest pain as presenting symptom. Except for Aspirin loading and use of beta blocker no other antischemic, statin or ACE/ARB medication was used for management of type II MI. All patients with Type II MI were managed by primary care teams. 3 patients developed NSTEMI and were managed by primary care teams with Cardiology consults. Anti-coagulation was considered for all patients. All patients received Aspirin loading, high intensity statin and beta blockers.

Conclusions:
Majority of patients with ACS had symptoms related to SARS-CoV-2 infection and chest pain was absent in 95% of cases. The most common ACS was type II MI- myocardial ischemia in context of hypoxia and the treatment was focused in treating the underlying cause rather than initiation of classical guideline directed therapy or invasive management. There were no cases of unstable angina and STEMI, results consistent with previous studies underlying the low incidence of STEMI cases during this pandemic.
Abstract 17163: Prolonged Increase in Endothelium-Specific NOX2-Derived Cytosolic Oxidants Exacerbates Maladaptive Cardiac Remodeling in Ischemic Myocardium
Authors: Brinck Teixeira Rayane , Pfeiffer Melissa , Karbasiafshar Catherine , Sellke Frank W , Abid Ruhul
Published: November 2020

Introduction:
Global increase in reactive oxygen species (ROS) in endothelial cells (EC) plays major roles in cardiovascular disease (CVD). However, the precise role of ROS within specific compartments of ECs are not yet known. This study aims to address the role of endothelium-derived cytosolic ROS in myocardial infarction (MI).

Hypothesis:
We hypothesized that an extended exposure to increased NADPH oxidase 2 (NOX2)-derived cytosolic ROS in EC would result in a worse post-MI outcome.

Methods:
Binary conditional transgenic mice expressing NOX2 in an EC-specific manner (NOX2VE) were studied. NOX2VE mice were assigned to tetracycline (Tet)-ON (control) to turn off transgene, or without Tet as Tet-OFF, i.e. NOX2-
O
ver
E
xpressing (NOX2VE-OE) groups. After 15 weeks of Tet-ON/OFF treatment, all mice were subjected to left anterior descending (LAD) coronary artery ligation that mimics acute MI (n=10/group). Left ventricle function was assessed by echocardiography 28 days post LAD. Ejection fraction (EF), fractional shortening (FS), left ventricle mass, wall thickness, heart rate, chamber diameter and volume at systole and diastole were analyzed by Student’s t-test.

Results:
Echocardiographic data showed that mice subjected to an increased NOX2-derived ROS in EC (NOX2VE-OE) presented with 19.3 ± 7.7% and 20.8 ± 7.9% decrease in EF and FS, respectively (p<0.05) compared to control (NOX2VE, Tet-ON). NOX2VE-OE mice showed an increase (by 14.1 ± 3.4%, p<0.01) in diastolic posterior wall thickness (DPWT) suggesting ventricular stiffness. NOX2VE-OE group also showed increased cardiac mass (by 14.0 ± 5.4%, p<0.05), which, along with DPWT indicates hypertrophy with a likelihood to develop heart failure. Interestingly, heart rate, systolic and diastolic chamber volume and diameters, stroke volume, and cardiac output showed no differences between the groups (p>0.05).

Conclusions:
Together, these results suggest that prolonged exposure to increased cytosolic ROS in coronary EC results in worse cardiac performance and myocardial stiffness, leading to a higher propensity to heart failure after MI. Currently,
in vivo
signaling studies are being carried out to understand molecular mechanisms by which NOX2-derived ROS in ECs result in impaired cardiac function.
Abstract 17165: Natural History of Cardiac Function in Patients With Atrial Fibrillation Pre- and Post- Ablation
Authors: Tang Lisa YW , Ho Kendall , Hawkins Nathaniel , Tam Roger , Lim Michael , Andrade Jason
Published: November 2020

Intro:
The natural history of cardiac function in atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) is incompletely described, as are heart rate patterns pre- and post-ablation.

Goals:
Examine autonomic status pre- and post-ablation using cardiac data (n=346) captured by implanted recorders

Methods:
Daily records (90-day pre to 365-day post ablation) were analyzed to extract parameters viz. heart rate variability (HRV), daytime heart rate (DHR) and nighttime heart rate (NHR). Analysis of variance was used to assess relationships between covariates (age, sex, etc.) and pre-post changes in parameters. We define "success" as patients who had no recurrence during post-ablation period per guidelines (“failed” otherwise).

Results:
Prior to ablation, mean DHR, NHR, and HRV were 69±10bpm, 60±9bpm, 122±32msec, respectively. After PVI, there was an immediate increase of ~5bpm in DHR (P<1e-4) and a more pronounced increase of ~11bpm in NHR (P<1e-4). HRV exhibited an immediate post-ablation peak decreasing by ~60msec (P<1e-4), with rapid recalibration over the first 10 post ablation days (increase of 20-25msec). Antiarrhythmic drug-use was a significant factor only in explaining changes in HRV (P=0.0126), while age was a significant factor only for the changes in DHR (P<1e-4). Comparing between subgroups, DHR and NHR were generally higher in the success than the failed group. At baseline, older patients (92 patients were of age>65years) had a significantly lower DHR and NHR than younger patients (117 were of age<56years). These age-based differences were amplified post ablation in DHR and NHR, but not HRV.

Conclusions:
PVI results in significant and sustained changes in heart rate parameters related to autonomic function. This relationship was observed globally, with the success group having significantly greater rises in DHR and NHR when compared to the failed group. Future work will explore whether these patterns exist in different cohorts.
Abstract 17174: Revisiting the QT Correction Formulas: A Generalized Additive Models for Location, Scale, and Shape Approach
Authors: Nguyen Hai , Jay Patrick Y , Scott William , Molnar Janos , Huang Henry , Somberg John C , Umapathi Krishna Kishore , Nguyen Hoang H
Published: November 2020

Introduction:
Various mathematical equations have been proposed to correct QT interval for heart rate (QTc). However, with most formulas, QTc remains dependent on heart rate (HR) especially at low and high HR values.

Hypothesis:
A spline correction function would perform better than standard mathematical formulas by allowing the data to determine the form of the relationship.

Methods:
A series of regression models using the generalized additive models for location, scale, and shape framework was applied to 10,000 completely normal electrocardiogram data from the National Health and Nutrition Examination Surveys II and III. Evaluation of the model’s performance was performed using the R
2
coefficient of determination and the root mean squared of the errors between the predicted and observed QTc. The new regression models were compared to the Bazett’s and Fredericia’s formulas, which are the 2 most widely used formulas in clinical practice.

Results:
When boxplots of the QTc for each formula are plotted, grouped by HR in intervals of 5 beats/minute, QTc determined by the penalized spline regression was almost heart rate independent for both male and female as the slope of the regression line was almost zero (-0.003 for female and -0.001 for male) (Figure 1 A—B). By contrast, QTc by Bazett had a positive correlation (regression slope of 0.86 for female and 0.89 for male) while Fredericia’s had a negative correlation (regression slope of -0.14 for female and -0.13 for male) with HR (Figure 1C—F). In all 3 formulas, there was no significant difference between male and female.

Conclusions:
A new QTc formula was developed, which is almost independent of HR thereby providing a more accurate estimate of QTc for clinical management. Automatic QTc calculation and percentiles estimation could easily be incorporated in an online calculator or app for easy integration in everyday clinical practice.
Abstract 17182: Coronary Endothelial Dysfunction in Humans is Associated With Elevated Expression of Clonal Hematopoiesis of Indeterminate Potential
Authors: Ganji Morsaleh , Lasho Terra , Toya Takumi , Ahmed Ali , Corban Michel , Lerman Lilach O , Patnaik Mrinal , LERMAN Amir
Published: November 2020

Introduction:
Recent evidence has demonstrated that Clonal Hematopoiesis of Indeterminate Potential (CHIP) increases the risk of cardiovascular events. However, the exact role played by CHIP in early stages of coronary atherosclerosis, characterized by coronary endothelial dysfunction remains to be elucidated.

Hypothesis:
The current study was designed to test the hypothesis that the presence of CHIP in peripheral blood cells is associated with coronary endothelial dysfunction and increased levels of inflammatory markers.

Methods:
Next generation sequencing was used to detect mutations among patients who had coronary endothelial dysfunction and control group (normal coronary endothelial function). Endothelial dysfunction was defined by ≥ 20% decrease in coronary artery diameter or ≤50% increase in blood flow in response to acetylcholine injection compared to baseline. Plasma cytokine levels of Interleukin (IL)-6 and IL-8 were also assessed.

Results:
Clonal hematopoiesis relevant gene mutations were found in 1 out of 64 patients with normal endothelial function (1.5%) and 11 out of 119 cases in the endothelial dysfunction group (9.2%) (P = 0.04) with ASXL1 (Additional sex combs-like 1) being the most frequent gene (4.2%) mutated. Cytokine analysis demonstrated that mutations in ASXL1, DNMT3A (DNA methyltransferase 3A) and TET2 (Ten-eleven-translocation-2) in the endothelial dysfunction group were associated with increased levels of IL-6 and IL-8 (P = 0.001, P = 0.003; respectively).

Conclusions:
The current study supports a potential role for CHIP in mechanisms of coronary artery disease starting at early stage of atherosclerosis. Furthermore, enhanced expression levels of IL-6 and IL-8 seem to be related to mutations in DNMT3A, ASXL1 and TET2 genes, more than other gene mutations relevant CHIP.
Abstract 17186: Molecular Mechanisms Underlying Sex-Related Differences in Mitochondrial Response to Myocardial Ischemia/Reperfusion
Authors: Wang Meijing , Scott Susan , Yu Qing , Singh Kanhaiya , Sen Chandan , Turrentine Mark
Published: November 2020

Introduction:
Cardiac dysfunction adversely impacts patient outcomes following surgically induced myocardial ischemia/reperfusion (I/R). Maintaining mitochondrial activity is crucial to reducing myocardial I/R. Inflammation and oxidative stress triggered by I/R impair mitochondria. Our group has shown sex differences in myocardial functional recovery after I/R. Here, we determined whether sex disparity in mitochondrial response to inflammatory mediator - TNFα and to reactive oxygen species - H
2
O
2
is responsible for sex differences in cardiac dysfunction. Given the key role of mitochondrial connexin43 (Cx43) in cardiac protection initiated by ischemic preconditioning, we also investigated the implication of Cx43 in sex-related mitochondrial response.

Methods:
Cardiomyocytes (male & female; C57BL/6 & doxycycline inducible Tnnt2-controlled Cx43 knockout) were subjected to simulated I/R (20’ I/60’ R), TNFα (10ng/ml), or H
2
O
2
(50 μM), +/- 17β-estradiol (E2).Mitochondrial membrane potential (ΔΨm) analyzed by JC1 red to JC1 green fluorescence intensity ratio (Fig. A) and mitochondrial respiration capacity by Seahorse XF Cell Mito Stress Test were determined.Cx43 was assessed in mitochondria by Western blots and Immunoelectron microscopy.

Results:
Improved ΔΨm (Fig. B) and preserved mitochondrial respiratory capacity were observed in female cardiomyocytes than in male ones following simulated I/R, TNFα, or H
2
O
2
.E2 restored mitochondrial activity in cardiomyocytes (Fig. C, D). In addition, E2 increased Cx43 content and phosphorylation in cardiac mitochondria. Ablation of cardiac Cx43 abolished E2-mediated mitochondrial protection during TNFα or H
2
O
2
challenge (Fig. E).

Conclusions:
Female cardiomyocytes were more resistant to I/R, TNFα, or H
2
O
2
stimulation than age-matched males, with greater protective role of mitochondrial Cx43 in female hearts. E2 usage regulated mitochondrial Cx43 and preserved cardiac mitochondrial performance.
Abstract 17187: Misinterpretation of Q-waves in Ventricular Septal Defect and Tetralogy of Fallot Patients by Non-Adult Congenital Heart Disease Specialists
Authors: Thorp Audrey , Hajduczok Alexander , Bhatnagar Sudhanshu , Shah Ravi , Davidson William R
Published: November 2020

Introduction:
Tetralogy of Fallot (TOF) and Ventricular Septal Defect (VSD) patients have non-diagnostic Q-waves within inferior (II, III, aVF) or septal (V1-V2) leads on ECG, perhaps due to incomplete conduction through septal defects. Non-diagnostic Q-waves tend to either be wide within a single lead, or deep (3-4mm) in contiguous leads, but do not meet diagnostic criteria for infarct.

Hypothesis:
Non-Adult Congenital Heart Disease (ACHD) physicians may inaccurately characterize non-diagnostic Q-waves as pathologic opposed to expert interpretation by ACHD-trained physicians in VSD and TOF patients. Thus, misinterpreting ECGs to suggest prior infarct and decreasing their positive predictive value (PPV).

Methods:
With application of pre-specified inclusion and exclusion criteria, we retrospectively reviewed 72 ECGs from TOF or VSD patients at Penn State Hershey Medical Center from 2002-2020 that were separately read by ACHD and non-ACHD specialists. Primary outcomes were ECGs with diagnosed Q-waves in two separate distributions, inferior or septal leads, by both groups using standard criteria for Q-wave infarct. Reported measures were sensitivity, specificity, PPV, and negative predictive value (NPV).

Results:
The 72 subjects with isolated TOF or VSD had a mean age of 39 years and 63% were male. Total disease prevalence (presence of Q-waves) was 4.6%. Q-wave infarct diagnosed by non-ACHD physicians had a sensitivity and specificity of 33% and 74% respectively. Their PPV was 5.87% and NPV was 95.85%.

Conclusions:
This retrospective cohort analysis of TOF and VSD patient ECGs showed the low PPV of non-ACHD physician diagnosis of Q-waves in this respective population. Misinterpretation and misdiagnosis of infarct based off ECG, has ramifications for both the patient and medical system as a whole. Sequelae include, but are not limited to, increasing patient risk for unwarranted medical treatment and affecting hospital billing and insurance coverage.
Abstract 17189: Explaining the Deep Learning Black Box by Identifying Segments of the Single-Lead ECG Signal Used for Detection of Atrial Fibrillation
Authors: Ivaturi Praharsh , Gadaleta Matteo , Pandey Amitabh C , Pazzani Michael , Steinhubl Steven R , Quer Giorgio
Published: November 2020

Introduction:
Deep learning (DL) has proved effective for automatic identification of atrial fibrillation (AF) using single-lead ECG. Adoption and trust of DL by clinicians is limited by its black box nature.

Hypothesis:
Post hoc explanations can elucidate what part of ECG signal is used by the black box DL algorithm, quantifying the importance of clinically relevant features in the classification decision. Making DL decision process transparent will help its integration into clinical practice.

Methods:
8,528 single-lead ECG recordings collected using AliveCor devices (PhysioNet) were used. Each signal was labeled as normal sinus rhythm, AF, other arrhythmia or noise. DL automatic classification involves a lightweight convolutional neural network architecture - MobileNet - whose performance is analyzed with an explanation method for DL.

Results:
Each RR interval is divided into 8 equal segments, where segment 1 follows each R peak, 4 and 5 correspond to the isoelectric baseline, and 7 to the P wave. The explanation method substitutes one of these segments with a straight line, and the corresponding change in sensitivity highlights its importance for the DL algorithm decision. MobileNet achieved a sensitivity of 92.5% to identify AF (9.4% of ECGs were in AF). Sensitivity increases by 2.5% when Segment 7 is removed, indicating that the absence of P wave leads the network to classify more frequently samples as AF.(Figure) When Segments 4 and 5 are removed, the sensitivity decreases by 2.5% and 5.0%, and by 26.7% when removed together. When all RR intervals are normalized to the same value (RR in the Figure), sensitivity for AF drops by 78.3%, showing that RR intervals are key for AF detection by DL algorithm.

Conclusions:
Post hoc explanations for AF detection by DL from single-lead ECG show the importance of common morphological features used for classifying AF. These methods can be used to understand the decision-making process of DL and motivate its clinical adoption.
Abstract 17191: Left Atrial Volume Index and E/E’ Predict Predominance of Post-Capillary Pulmonary Hypertension With Exercise Hemodynamics
Authors: Dharmavaram Naga , Baber Aurangzeb , Masri Sofia C , Dhingra Ravi , Runo James , Chesler Naomi C , Raza Farhan
Published: November 2020

Introduction:
Post-capillary pulmonary hypertension (PH) is diagnosed with rest hemodynamics and requires management of left heart disease. However, in subclinical PH and mixed PH (mixed pre- and post-capillary), it is imperative to identify a predominant post-capillary phenotype with exercise (aka. Pulmonary venous hypertension).

Hypothesis:
In suspected subclinical and mixed PH, greater left atrial volume index (LAVI; >35) and E/E’ (>8) on echocardiogram can reliably predict a predominant post-capillary PH with exercise, assessed with invasive cardiopulmonary exercise testing (iCPET).

Methods:
We reviewed clinical, echocardiographic and iCPET data for 37 patients undergoing exercise right heart catheterization and then analyzed the data with receiver operator curve (ROC) and area under the curve (AUC) analysis to estimate the different echo parameters to identify post-capillary PH.

Results:
Within the cohort, mean age (± SD) was 63.6±11.3 years, and 19 subjects were female (51%). On ROC analysis, LAVI and E/E’ had high predictive ability to identify a pulmonary venous hypertension response with exercise (AUC=0.860, p=0.003 for LAVI, and AUC=0.788, p=0.014) with optimal cut-offs identified as: LAVI >35 and E/E’ >8. These variables also notably had a significant association with PCWP/CO>2. To understand the hemodynamics associated with these differentiable echo features, we divided the overall cohort (n=37) into 2 groups:

group 1 (
Abnormal-LA group
)

=LAVI>35 and/or E/E’ >8,

group 2 (
Normal-LA group

)=LAVI≤ 34 and E/E’≤8. The LAVI in group 1 vs group 2 was: 44.3±15.2 vs 23.1±4.4 (p<0.001) and E/E’ was: 15.8±9.9 vs 7.7±1.95 (p<0.01). Results are summarized in Table 1.

Conclusions:
Among individuals with suspected PH, LAVI>35 and E/E’ >8 are reliable non-invasive markers to identify post-capillary PH. In a patient with a new diagnosis of PH based on screening echocardiogram, LAVI≤ 34 and E/E’≤8 may identify a patient who is likely to benefit from PH drugs.
Abstract 17208: Successful Implementation of Grip Strength Measurement as a Frailty Screening Tool
Authors: Kim Gloria Y , Gangadharan Arati A , Brown Craig S , Osborne Nicholas H , Corriere Matthew
Published: November 2020

Introduction:
Objective screening for frailty is seldom performed because existing tools are time consuming and usually applied post-hoc. Implementation of efficient and feasible frailty screening approaches within clinic is needed.

Purpose and hypothesis:
We implemented grip strength measurement as a frailty screening tool in a cardiovascular clinic setting and compared this to existing frailty assessment tools, including the modified frailty index-5 (mFI-5) and -11 (mFI-11). We hypothesized that grip strength would be comparable to the mFI-5 and -11, associated with common adverse events including urinary incontinence (UI) and falls, and increased diagnosis of frailty would occur as a result implementation.

Methods:
Grip strength measurement was integrated into clinic intake to screen for weakness, a frailty component. Measurements were performed routinely for cardiovascular clinic visits and entered into the EMR data field. Categorical frailty was assessed based on 20
th
percentile for grip strength (kg) adjusted for gender and BMI. A “dotphrase” statement was built to streamline clinical documentation, and quarterly newsletters were used to disseminate coding and other related information. Categorical tests were used to evaluate associations between grip, weakness, and other measures of frailty.

Results:
A total of 4,447 unique patients had grip strength measured. Mean age was 63.3±15.6, BMI 29.6±7.0, 47.6% (n=2,115) were female, and 86.5% were Caucasian/White. Based on grip strength, 34.6% (n=1,538) were weak, and 22.0% (n=980) and 16.9% (n=754) were frail based on mFI-5 and mFI-11, respectively. Less than 10% (n=408, 9.25%) had a history of falls and 39 (0.88%) had UI. Falls were associated with weakness (P<0.001) but UI was not. Only 45 (1.01%) had a coded frailty diagnosis in the EMR. Among those with a frailty diagnosis, 35 (77.8%) were considered frail by grip. The negative predictive value (NPV) of the grip strength when mFI-5 is used as the gold standard is 0.84.

Conclusions:
Grip strength is both feasible and practical for frailty screening in clinical environments. Mismatch between screening-based and coding-based frailty prevalence suggests an opportunity to improve risk screening through routine grip strength assessment.
Abstract 17213: Myocardial Infarction and Stroke Awareness Among US and Foreign-Born Adults in the 2014 and 2017 National Health Interview Survey
Authors: Mannoh Ivy , Turkson Ocran Ruth Alma N , Commodore-mensah Yvonne
Published: November 2020

Background:
Atherosclerotic cardiovascular disease, defined as nonfatal myocardial infarction (MI), coronary heart disease death, or fatal or nonfatal stroke, is the leading cause of death in the United States (US). MI and stroke symptom awareness reduces delays in hospitalization and mortality. We hypothesized that foreign-born persons will have lower stroke and MI symptom awareness than US-born persons.

Methods:
We analyzed cross-sectional data from the 2014 and 2017 National Health Interview Surveys (NHIS) on US-born and foreign-born adults from 9 regions of birth (Europe, South America, Mexico/Central America/Caribbean, Russia, Africa, Middle East, Indian subcontinent, Asia, and Southeast Asia). Our outcomes were stroke and MI symptom awareness, and the best action to take during a stroke or MI event. Awareness was defined as knowing all 5 symptoms of MI or stroke respectively, and choosing “call 911” as the best action to take in the event of an MI or stroke. Generalized linear models with Poisson distribution and a logarithmic link was used to assess disparities in awareness between foreign-born and US-born persons. We compared responses from 2014 and 2017 to assess improvement in awareness.

Results:
We included 63,439 participants, with mean age 38.2 years; 51% were female and 50% had less than high school education. After adjusting for age, sex, and education, we observed significant variation in MI and stroke symptom awareness and best action to take by region of birth [Table]. In comparison to US-born, foreign-born persons were less aware of MI and stroke symptoms and the best action to take. Improvement in awareness was not significant in all groups between 2014 and 2017.

Conclusion:
These findings suggest a disparity in MI and stroke symptom awareness among immigrants in the US. Culturally tailored public health education and health literacy initiatives are needed to help reduce these disparities in awareness.
Abstract 17219: Non-Invasive, Blood-Free Point of Care Test to Rapidly Exclude Myocardial Injury: The AI ECG
Authors: Attia Zachi I , Sandoval Yader , Carter Rickey , Kapa Suraj , Lopez-jimenez Francisco , Noseworthy Peter A , Jaffe Allan S , Friedman Paul
Published: November 2020

Background:
Myocardial injury results in release of cardiac troponin (cTn) into the bloodstream, readily detected by high-sensitivity cTn (hs-cTn) assays. A noninvasive, rapid, home-based test to exclude acute myocardial injury at the time of the test and for the next 7 hours would help manage patients with suspected myocardial infarction. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could identify absence of injury.

Objective:
To train and test an AI-ECG convolutional neural network (CNN) to identify patients using a single ECG who are suspected of myocardial infarction who are low risk, with hs-cTn levels below the 99
th
percentile at test time and for the subsequent 7 hours.

Methods:
A CNN tuned to identify the absence of a hs-cTnT (5
th
Gen cTnT Roche Diagnostics) >15ng/L for men and >10ng/L for women was developed. All ECGs were recorded within one hour of the hs-cTnT assay. We used 73,012 ECGs and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 11,904 ECGs with 21,191 hs-cTnT measurements up to 7 hours after the ECG, from 11,904 different patients as a holdout test set.

Results:
The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. 5,852 patients (49.1%) had no elevation of hs-cTnT and 6,052 (50.9%) had an hs-cTnT above the 99
th
percentile at baseline or within 7 hours of the test. Of the 11,904 patients in the test set, using a sensitive threshold, the 12 lead AI ECG identified 1037 patients (8.7%) likely to have a low risk for subsequent hs-cTnT increases > 99
th
% (AUC 0.86), and the single lead ECG identified 685 patients. Of the 1037 low risk pts, 59 had an hs-cTnT > 99
th
percentile within 7 hours. The mean maximum hs-cTnT among the 59 low-risk patients was 53 ng/L ± 92 vs 184 ng/L ± 1474 in the others. None of these low risk patients died within 14 days of the test.

Conclusion:
Use of the AI ECG to identify patients without cardiac injury at the time of the test and for 7 subsequent hours is feasible. This may permit rapid, point of care, home-based, bloodless, painless testing to exclude cardiac injury, facilitating care and management of patients with suspected ischemia.
Abstract 17229: Predictors of 30 and 180 Days Readmissions After Transcatheter Aortic Valve Replacement in the United States
Authors: Shafi Irfan , Mishra Tushar , Mir Tanveer , Akers Katherine , Yazdanpanah Omid , Sebastian Joseph , Alkhouli Mohamad
Published: November 2020

Background:
Readmission rates are a widely accepted quality indicator. Our objective was to study characteristics of readmissions at 30 and 180 days after Transcatheter Aortic Valve Replacement (TAVR).

Methods:
Patients undergoing TAVR between 2016 and 2017 in the U.S. Nationwide Readmission Database were evaluated for the rates, causes, predictors, and mortality of readmission at 30 and multiple readmission within 180 days after index discharge.

Results:
This analysis included 89601 hospitalizations; 13% were readmitted within 30 days and 8.7% were readmitted multiple times within 180 days. Most important predictors of readmissions, were Length of stay >5 days during index hospitalization (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.47-1.71 at 30 days & HR 1.72; 95% CI 1.58-1.87 at 180 days), > 4 Charlson comorbidities (HR 1.27; 95% CI, 1.19-1.34 at 30 days & HR, 1.54; 95% CI, 1.44-1.65 at 180 days), discharge to skilled nursing facility (HR, 1.34; 95% CI, 1.24-1.44 at 30 days & HR, 1.49; 95% CI, 1.36-1.65 ), atrial fibrillation (HR, 1.25; 95% CI, 1.18-1.32 at 30 days & HR, 1.35; 95% CI, 1.26-1.45 at 180 days), Transapical TAVR approach (HR, 1.21; 95% CI, 1.04-1.42 & HR, 1.20; 95% CI, 1.01-1.43 at 180 days), and acute kidney injury (HR, 1.22; 95% CI, 1.12-1.32 at 30 days & HR, 1.1; 95% CI, 1.01-1.21 at 180 days)(Figure 1 A,B). 67% patients were readmitted at least 1 time within 180 days, 22% were readmitted 2 times within 180days and 11% were readmitted more than 3 times within 180 days. Readmissions were because of noncardiac causes in 67.8% of cases and because of cardiac causes in 32.2% of cases.

Conclusion:
The study demonstrates that baseline comorbidities alongside non-cardiac causes contributed significantly to readmissions after TAVR at both 30 days and 180 days. The results help to target the susceptible patients in both short as well as long term and to provide evidence-based interventions to reduce the risk and financial burden associated with readmissions.
Abstract 17232: Cardiopulmonary Exercise Testing in Diabetic Chronic Heart Failure Patients With Microalbuminuria
Authors: tabucanon Thida , Engelman Timothy , Bhattacharya Sanjeeb S , Finet J Emanuel , Tang Wai Hong W
Published: November 2020

Introduction:
Microalbuminuria can be a presentation of microvascular complication in diabetes mellitus (DM).

Hypothesis:
Microalbuminuria is associated with impaired exercise performance in chronic HF with DM patients.

Methods:
We retrospectively analyzed a cardiopulmonary exercise testing (CPET) database in 255 chronic HF patients with DM that had urine microalbumin test between December 2012 and September 2019. Demographic data and CPET parameters were compared between the patients who had and had not microalbuminuria which was defined by microalbumin/creatinine ratio ≥ 30 mg/g. Peak oxygen consumption (peak VO
2
) ≤ 14 ml/kg/min and ≤ 12 ml/kg/min if had history of beta-blocker uses were classified as low peak VO
2
and used in multivariable analysis.

Results:
There were a total 92 patients (36.1%) that had microalbuminuria. Mean age was not significant different between the patients with and without microalbuminuria (57.7 vs 59.4 years, p = 0.26). The patients with microalbuminuria had lower body mass index (BMI; 30.8 vs. 32.7 kg/m
2
, p = 0.014) and had more history of beta-blocker (BB) uses (81.5% vs. 69.3%, p = 0.038), no significant different in other medication uses. Left ventricular ejection fraction (LVEF) was significant lower in patients with microalbuminuria (35.8% vs. 41.5%, p = 0.028). The patients with microalbuminuria had significant higher prevalence of low peak VO
2
(45.7% vs. 30.1%, p = 0.015) and lower peak stroke work (VO
2
/HR; 11.5 vs. 12.8 ml/ beat, p = 0.008). No significant different in ventricular efficiency slope (VE/VCO
2
; 37.1 vs. 35.4, p = 0.094), Multivariable analysis showed that proteinuria was independently associated with low peak VO
2
after adjusted for age, sex, BMI LVEF, history of BB uses, VE/VCO
2
and HR at peak VO
2
, (odds ratio = 3.83, p < 0.001).

Conclusions:
Microalbuminuria was independently associated with low peak oxygen consumption in chronic HF with DM patients.