bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15056: Machine Learning Prediction of Long QT Syndrome
Authors: Simon Steven , Mandair Divneet , Rosenberg Michael A , Tiwar Premanand
Published: November 2020

Introduction:
Drug-induced QT prolongation causes significant morbidity and mortality but could be preventable with prediction of susceptible individuals. Machine learning (ML) algorithms applied to electronic health record (EHR) data may provide a method for identifying these individuals and could be automated to directly alert providers of risk. This study applies ML techniques to EHR data to identify an integrated model that can be deployed to predict risk of drug-induced QT prolongation.

Methods:
We examined data from the UCHealth EHR that has been harmonized to the Observational Medical Outcomes Partnership common data model and identified inpatients who had received a medication known to prolong the QT interval and had an electrocardiogram (ECG) performed within 24 hours. We used a binary outcome of the development of a QTc interval > 500 ms by ECG within 24 hours of medication initiation or no ECG with a QTc interval > 500 ms throughout the encounter. We compared multiple machine learning methods (logistic regression, random forest, naïve Bayes, and deep neural network (DNN)) by classification accuracy as assessed by AUC and F
1
score. We performed calibration and scaling of the final model.

Results:
We identified 35639 inpatients who received a known QT-prolonging medication and had an ECG within 24 hours. Of those, 4558 patients developed a QTc > 500 ms and 31081 patients did not. The DNN model provided reasonable classification accuracy (F1 score 0.404; AUC 0.71) and was the most accurate method tested. A range of decision cutpoints were plotted with respective sensitivity/specificity (Figure 1).

Conclusions:
We found that by applying a DNN to EHR data, we could reasonably predict individuals susceptible to drug-induced QT prolongation. Varying cutpoints can be used to tailor the model to the desired sensitivity. Future studies are needed to validate this model in novel EHRs and within the physician order entry system to assess ability to improve patient safety.
Abstract 15063: The Atf6-inducible Selenoprotein, Vimp, Regulates Proteostasis and Pressure Overload-induced Heart Failure
Authors: Blackwood Erik , Thuerauf Donna , MacDonnell Lauren , Bilal Alina S , Glembotski Chris C
Published: November 2020

Introduction:
Cardiac hypertrophy is associated with an increase in protein synthesis, which must coordinate with protein folding and degradation to allow for homeostatic growth without affecting the functional integrity of cardiac myocytes (i.e. proteostasis). There is a

gap in our understanding

of how proteostasis becomes imbalanced during chronic pathological hypertrophy.

Hypothesis:
The

objective

of this study to examine the mechanisms regulating the protein degradation aspect of proteostasis, ER associated degradation (ERAD), by focusing on the role in cardiac hypertrophy of the unique selenoprotein and functional initiator of the ERAD molecular machinery, VIMP, which is induced in cardiac pathology by the nodal proteostasis transcription factor, ATF6.

Methods and Results:
VIMP was increased in failing human and in mouse hearts subjected to TAC-induced heart failure in an ATF6-dependent manner. AAV9-shRNA-mediated VIMP knockdown in the heart dramatically suppressed cardiac hypertrophy and staved off decompensation and heart failure, while AAV9-mediated VIMP overexpression exacerbated cardiac decompensation in response to TAC, an effect not observed with overexpression of an ERAD-null mutant of VIMP. Unexpectedly, VIMP knockdown enhanced ERAD-mediated degradation of the cytosolic pro-hypertrophic kinase, serum/glucocorticoid-regulated kinase 1, SGK1. Furthermore, AAV9-mediated overexpression of SGK1 negated the beneficial effects of VIMP knockdown; knockdown of the SGK1-binding protein, GILZ enhanced ERAD-mediated degradation of SGK1 and blunted cardiac hypertrophy. A peptide inhibiting the SGK1-GILZ interaction enhanced the ERAD-mediated degradation of SGK1 and ameliorated agonist-induced cardiac myocyte hypertrophy.

Conclusions:
Here we studied ERAD for the first time in any organ,
in vivo
, finding that an ATF6-inducible selenoprotein, VIMP, regulates the ERAD-dependent degradation of SGK1, thus accelerating TAC-induced cardiac decompensation and heart failure.
Abstract 15067: Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes Mellitus - Findings From the Look Ahead Trial
Authors: Patel Kershaw V , Bahnson Judy , Gaussoin Sarah , Johnson Karen C , Pi-Sunyer Xavier , White Ursula , Olson KayLoni L , Bertoni Alain G , Kitzman Dalane W , Berry Jarett D , Pandey Ambarish
Published: November 2020

Introduction:
Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes mellitus (T2DM). However, the contribution of changes in body composition measures [lean mass (LM), fat mass (FM), waist circumference (WC)] to the risk of HF and myocardial infarction (MI) is not well-known.

Methods:
Adults with T2DM who had overweight or obesity enrolled in the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. LM and FM were predicted using validated equations and compared with DXA measurements. Adjusted Cox models were used to evaluate the associations of baseline and longitudinal changes in LM, FM, and WC over 1- (Y0 to Y1) and 4-year (Y0 to Y4) follow-up with risk of overall HF, HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) and MI.

Results:
Among 5,103 participants, there were 257 incident HF events over 12.4 years of follow-up. Predicted and measured LM and FM were highly correlated (R
2
=0.87-0.92). LM and FM decreased with greater declines in the intensive lifestyle intervention arm (Figure 1A). In adjusted analyses, baseline measures of body composition were not significantly associated with risk of HF. Decline in FM, but not LM, over 1- and 4-year follow-up was significantly associated with lower risk of HF (Figure 1B). A significant association was observed between decline in WC and risk of overall HF and HFpEF but not HFrEF. Among adults without a history of CVD, changes in body composition were not associated with risk of MI.

Conclusions:
In adults with T2DM who had overweight or obesity, a lifestyle intervention is associated with significant loss of FM and LM. Decline in FM and WC, but not LM, were each significantly associated with lower risk of HF but not MI. Furthermore, decline in WC was significantly associated with lower risk of HFpEF but not HFrEF.
Abstract 15069: Long Term Heart Failure Risk in Zika Myocarditis
Authors: mendoza ivan , Gonzalez Karina , Medina Jose I , Morr Igor , Meza Yolimar , Urbaez Elias , Carmen Terzic , Finizola Vicente , Lopez-jimenez Francisco , Martinez Nahir , Mendoza Ivan
Published: November 2020

Introduction:
It has been estimated that up to a billion people worldwide could be exposed to Zika re-emergence including North America. Zika was considered the worst outbreak of the century before COVID-19. There are only few reports of cardiac complications and the long-term risk of heart failure (HF) is unknown. This is the objective of this study.

Methods:
We included 19 patients who developed acute myocarditis within one week of symptomatic Zika, in a prospective observational multi-center study. Patients underwent clinical, laboratory evaluation including Zika confirmation, ECG, echocardiogram, Holter, cardiac MRI, coronary arteriography (2). Patient follow-up examinations were performed at 2, 6,12, 24, 36 and 48 months.

Results:
Of the 19 patients, 12 (63%) were female with a mean age of 49 ± 17 years with a median follow-up of 3 years. Nine patients (47%) developed acute HF; 8 (42%) with reduced ejection fraction (HFrEF) and one with preserved EF (HFrEF) and moderate to severe pericardial effusion. Two cases died suddenly in the first week of Zika onset, both with HFrEF. Treatment included sacubitril /valsartan, or ace-inhibitors, SGLT2 inhibitors, beta-blockers, aldosterone-blockers, cardiovascular rehabilitation, and in one case cardiac resynchronization therapy plus implanted defibrillator. There was no new HF onset after the acute phase of the disease. Myocarditis resolved in 10 (56%) patients. Persistent atrial and ventricular arrhythmia with normal EF observed in 5 (26%) of cases. Altogether, characteristic features of dilated cardiomyopathy that developed in 7 patients (36, 8%); 2 (11%) of them died.

Conclusion:
Almost half of the patients with Zika myocarditis developed acute HF during the first week of disease onset, none of the patients developed HF after the acute phase. A 3-year mortality rate of 10,5 % was observed.
Abstract 15084: A Retrospective Analysis of Atrial Fibrillation Patients Aged 80 Years and Older Prescribed a Low-dose Non-vitamin K Antagonist Anticoagulant
Authors: Chaudhry Usman A , Ezekowitz Michael , Gracely Edward J , Wolfe Catrina M , Harper Grace M , Harper Glenn
Published: November 2020

Background:
The very elderly and those receiving low doses of the direct-acting oral anticoagulants (DOACs) were underrepresented in trials leading to the approval of Apixaban 2.5 mgs BID (A), Rivaroxaban 15mgs daily (R) and Edoxaban 30 mgs daily (E). Approval of dabigatran 75mgs BID (D) was based entirely on pharmacokinetic studies.

Methods:
Retrospective analysis of the electronic medical record of a multi-disciplinary practice of 396,064 patients between 1/1/11 (when first DOAC available) and 5/31/17.

Results:
9,446 patients had Atrial Fibrillation (AF), with 2,660 prescribed a DOAC and 846 at the low dose with 514 ≥ 80 yrs (range 80 – 98) with a mean CHA
2
DS
2
-VASc score of 4.5, which did not differ between patients prescribed D, R or A (p = 0.66 by ANOVA). Fifty-three patients received D, first used on 2/26/11, 223 R, first used on 12/15/11, and 236 A, first used on 6/19/12, and one patient received E. Among 28 baseline variables there were no clinically relevant differences among D, R, and A. All outcomes were reported as time to
first
event. All-cause mortality, n = 5 (5.5%/yr) for D, n =15 (4.2%) for R, and n = 23 (9.5%) for A, p = 0.031 by log rank test (with A > R by pairwise log-rank, p = 0.013). Major bleeding n = 13 (14.3%/yr) for D, n = 50 (14.1%) for R, and n = 22 (9.1%) for A, p = 0.048 by log rank test (with A < R, p = 0.017). Intracranial bleeding n = 2 (2.2%/yr) for D, n = 6 (1.7%) for R, and n = 2 (0.8%) for A, p = 0.53. There were 7 ischemic strokes or systemic embolic events (SSE) in total (1.1%/yr): D, R, and A (p = 0.94). Comparisons involving D may be underpowered. 245 patients (47.7%) remained on their prescribed drug without an event for the observation period (p = 0.55).

Conclusion:
D, R and A were well tolerated in patients ≥ 80 yrs, with low SSE and intracranial bleed rates. Major bleeds were the most frequent outcome, lowest in patients prescribed A. A had a higher all-cause mortality.
Abstract 15095: CSHA Frailty Scale as a Predictor of Hospital Readmission After PCI
Authors: Raynak John , Cowherd Michael , Yang Hannan , Sherrill Clay , Rossi Joseph
Published: November 2020

Introduction:
The Canadian Study on Health and Aging (CSHA) Frailty Scale was included in the National Cardiovascular Data Registry’s (NCDR) CathPCI registry beginning April 2018. The value of this frailty assessment as an independent predictor of hospital readmission is unknown.

Methods:
A retrospective analysis was performed of patients who underwent PCI within the University of North Carolina Medical System between 04/2018 and 12/2018. Outcome data was obtained from our electronic medical record data repository and procedural data from the institutional CathPCI registry. The primary outcome was repeat hospital admission within 1 year of PCI. Significant covariates (p<0.05) in the univariate analyses were considered for inclusion in the multivariate model. Multivariate logistic regression was then performed to determine if CSHA Frailty Scale was an independent predictor of hospital readmission.

Results:
1,592 subjects were identified with 367 readmission events. Patients in the readmission cohort were older, had a higher frailty score, and had more comorbidities. Table 1 summarizes the comorbidities included in the logistic regression. CSHA Frailty Scale did not meet significance requirements (P<.05) to be independently associated with readmission. Covariates that were significant independent predictors of readmission included age (OR 1.024, 95% CI 1.012-1.036); cerebrovascular disease (OR 1.688, 95% CI 1.234-2.308); dialysis (OR 2.983, 95% CI, 1.583-5.622); and CHF (OR 2.465, 95% CI, 1.851-3.282).

Conclusions:
The CSHA Frailty Scale was not independently associated with readmission in the setting of PCI in our health system. This particular assessment of frailty may not provide added value over traditional comorbidities in this patient population.
Abstract 15097: Covid-19 and Cardiovascular Complications: Pooled Analysis of Observational Studies
Authors: Samala Venkata Vikramaditya Reddy , Gupta Rahul , Aedma Surya Kiran , Andrus Bruce W
Published: November 2020

Introduction:
The pandemic of COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection. Studies published so far raise concerns for cardiac complications in the infected individuals.The aim of our study is to determine the prevalence of cardiac complications in COVID-19.

Methods:
A systematic electronic search was performed in PubMed, Embase, Google Scholar. Retrospective studies having original hospitalized patient data were included in our study; while studies focussed only on intensive care unit (ICU) patients were excluded to prevent selection bias. Pooled analysis using a random effects model (Mantel-Haenszel test) was performed to look at the incidence of troponin elevation and association between elevated troponin levels, admission to the ICU and associated mortality.

Results:
18 studies from 6 countries with over 9,500 patients were included in our analysis. Troponin elevation was reported in 16% (1123/7130) of patients. Heart failure was reported in 1 study and cardiac arrhythmia was reported in 2 studies. Elevated troponin levels were associated with higher rates of ICU admission (OR 26.17, 7.06-96.94; p<0.01) and mortality (OR 27.22, 10.24-72.33; P<0.01) (Figure 1). Information regarding the degree of troponin elevation and etiology associated with it (myocarditis vs acute coronary syndrome vs stress induced from critical illness) was not reported.

Conclusion:
Heart failure was reported in around 20% of the patients in 1 study, while troponin elevation was seen in 16% of the patients in 10 different studies. This is similar to the rate of cardiac complications reported in severe community acquired pneumonia. Troponin elevation in itself was associated with higher rates of ICU admission and mortality. This should alert the clinicians to check for troponin levels in these patients and triage them accordingly. More studies are needed to better understand specific mechanisms of cardiac injury in COVID-19 patients.
Abstract 15390: Outcomes in Patients Hospitalized With Influenza-related Myocarditis in the United States: A Nationwide Study
Authors: Uzomah Uwajachukwumma A , Khaloo Pegah , Shaqdan Ayman , Ledesma Pablo A , Galvin Jennifer , Ptaszek Leon , Ruskin Jeremy N
Published: November 2020

Introduction:
Acute myocarditis is a serious complication of influenza. While current reports suggest that subclinical cardiac involvement may be transient, myocarditis has been implicated in up to a third of sudden deaths in patients with influenza.

Methods:
Patients hospitalized with influenza in the US between 2003 and 2017 were identified using the Nationwide Inpatients Sample. They were subsequently classified to specify those with and without a diagnosis of myocarditis and specific outcomes of interest were compared between these subgroups.

Results:
: Between 2003 and 2017, 1,187,615 patients were hospitalized with influenza in the US. Of these, 2,430 patients (0.2%) were diagnosed with myocarditis while 1,185,185 patients (99.8%) did not have myocarditis. Patient characteristics and outcomes are shown in the table below. Independent predictors of myocarditis were: age (adjusted odds ratio [aOR]:0.98; 95% CI:0.98-0.99), male sex (aOR:1.21 ; 95% CI:1.01-1.46), Elixhauser score ≥3 (aOR:1.34; 95% CI:1.07-1.7), coagulopathy (aOR:1.67; 95% CI:1.29-2.17), valvular disease (aOR:1.5; 95% CI:1.07-2.1), abnormal weight loss (aOR:1.7; 95% CI:1.23-2.35), and a diagnosis of the 2009 H1N1 influenza virus (aOR:4.79; 95% CI:1.51-15.24). Independent predictors of death in patients hospitalized with influenza myocarditis were: age (aOR:1.04; 95% CI:1.01-1.06), stroke (aOR:11.16; 95% CI:1.57-79.49), shock (aOR:61.1; 95% CI:11.88-314.3), renal failure (aOR:3.56; 95% CI:1.2 -10.55), coagulopathy (aOR:2.62; 95% CI:1.04-6.6), and electrolyte disorders (aOR:3.19; 95% CI:1.07-9.47).

Conclusions:
Patients with influenza who develop myocarditis are younger than those without myocarditis and have more interventions, longer LOS and worse outcomes including a four-fold higher risk of cardiac arrest and a two-fold higher mortality rate. The strongest independent predictor of developing myocarditis was having the 2009 H1N1 influenza virus infection.
Abstract 15395: Immune Checkpoint Inhibitors for Cancer Are Associated With Increased Venous Thromboembolism Events
Authors: Gong Jingyi , Drobni Zsofia , Alvi Raza , Murphy Sean , Hartmann Sarah , Gilman Hannah , Zubiri Leyre , Raghu Vineet , Sullivan Ryan , Zafar Amna , Zlotoff Daniel A , Frigault Matthew , Karp-Leaf Rebecca , Reynolds Kerry , Neilan Tomas G
Published: November 2020

Introduction:
Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE.

Methods:
This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression.

Results:
Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE.

Conclusions:
Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.
Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients
Authors: Perino Alexander C , Pundi Krishna , Fan Jun , Schmitt Susan K , Kothari Mitra , Heidenreich Paul A , Turakhia Mintu
Published: November 2020

Introduction:
Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin.

Methods:
We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin.

Results:
The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin (
Table
). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest (
Table
).

Conclusion:
DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.
Abstract 15398: Standing Breathless: A Case of Platypnea-Orthodeoxia Syndrome
Authors: Vohra Adam S , Subramanyam Pritha , Singh Harsimran S
Published: November 2020

A 67-year old women with a history of metastatic endometrial cancer, prior pulmonary embolism (PE) (on Xarelto) and mitral valve prolapse presented for 2-3 weeks of exertional dyspnea. Patient presented to oncology clinic with oxygen saturation (SpO2) in the mid-70% on room air requiring supplemental oxygen, and eventually high flow nasal cannula (HFNC). She was transferred to our cardiac intensive care unit for further management of her hypoxia. Physical exam was notable for decreasing SpO2 from supine (99%) to sitting (88%) to standing (79%). In this patient with metastatic cancer, differential diagnosis for hypoxia was broad including pneumonia, metastatic pulmonary disease, doxorubicin-induced cardiomyopathy, and PE. CT chest showed no signs of pulmonary edema, pneumonia, lung metastases, or PE. Transthoracic echocardiogram showed normal left and right ventricular function with moderate aortic regurgitation and mitral regurgitation. However, agitated saline injection showed right to left flow consistent with intraatrial shunt. Transesophageal echocardiogram confirmed large patent foramen ovale (PFO) with atrial septal aneurysm. Given physical examination findings, presence of PFO, and structural abnormalities of intraatrial septum, platypnea-orthodeoxia syndrome (POS) was considered. Right heart catheterization was completed to evaluate shunt physiology and showed unremarkable pressures (RA 1, RV 22/1, PCWP 3, PA 20/3, and LA 2). Venous oxygen saturations did not show any step-up suggesting left to right shunt. Exercise challenge did not result in any significant change in PA or PCWP pressures. Given persistent concern for POS without other clear diagnosis, patient underwent percutaneous closure of PFO with a 30mm Gore Cardioform septal occluder. Patient had resolution of her exertional hypoxia following procedure and was discharged home the next day. The case discusses 1) the importance of history of and physical exam in narrowing diagnosis, 2) utilization of multimodality imaging to evaluate intraatrial shunts, and 3) use of percutaneous methods for PFO closure.
Abstract 15403: New-onset Atrial Fibrillation is Infrequent in Acute COVID-19 but Maybe Associated With Worse Outcomes
Authors: Yang Ruifang , Kalaveshi Sokol , Goldgrab David , Craig Jearim , Mester Stephen , Perzanowski Christian
Published: November 2020

Introduction:
The COVID-19 has reached pandemic status with significant morbidity and mortality including cardiovascular complications. Systemic inflammation caused by the COVID-19 infection has been associated with an intense release of multiple cytokines which directly cause myocardial injury. New-onset atrial fibrillation (noAF) is a common consequence of systemic inflammation in bacterial pneumonia as well as influenza and has been shown to have independently poorer outcomes.

Hypothesis:
We sought to determine the incidence and significance of noAF in patients with confirmed COVID-19 infection.

Methods:
We prospectively studied patients with acute COVID-19 infection admitted to our referral center between March and May 2020. Data of demographics, clinical features, comorbidities and complications were collected. Cardiac rhythms were observed using 12-lead electrocardiogram and continuous telemetry.

Results:
Total 62 patients were followed. The end-point included incidence of any episode of AF, cardiovascular death and total mortality. Mean age was 66 ±17 years, 56% were males, 37 patients without history of cardiac disease, 25 patients with documented cardiac disease including 31% of coronary artery disease (CAD), 28% of congestive heart failure (CHF), 11% of history of prior atrial fibrillation (hoAF). Four (6.5%) patients manifested noAF during hospitalization (95% CI, 1.8, 16). There was a significant difference in mortality between patients with and without cardiac diseases (P = 0.02) (Table). All patients with noAF required ventilation support and had significantly higher mortality compared to patients without cardiac disease (P < 0.05) (Figure).

Conclusions:
New-onset AF was infrequently observed, however was associated with a poorer prognosis for hospitalized patients with acute COVID-19 infection. Larger studies are needed to confirm these findings as well as identify measures of AF prevention in this population.
Abstract 15410: Post-operative Outcomes After Fontan Procedure in Patients With Heterotaxy and Other Situs Anomalies
Authors: Duong Son Q , Zaniletti Isabella , Lopez Leo , Sutherland Scott M , Shin Andrew Y , Collins Ronnie T
Published: November 2020

Background:
Heterotaxy is a multisystem disorder of situs often associated with cardiac, immune, and gastrointestinal abnormalities. Heterotaxy and other situs abnormalities (H/SA) may share ciliary dysfunction as an embryologic origin. Extracardiac manifestations of H/SA may contribute to increased morbidity and mortality after total cavopulmonary connection (Fontan) procedure. We hypothesized that patients with H/SA have worse postoperative outcomes after Fontan than patients without H/SA.

Methods:
We queried the Pediatric Health Information System (PHIS) database for hospitalizations with ICD-9/10 codes for Fontan procedure in patients aged 1 to 12 years from 2004 to 2019. Those coded for dextrocardia, situs inversus, asplenia/polysplenia, and atrial isomerism were defined as H/SA. Outcomes were in-hospital all-cause mortality or heart transplantation, post-operative ECMO, dialysis, postsurgical length of stay (LOS), and mechanical ventilation >4 days. Outcomes were compared between H/SA and non-H/SA controls with chi-squared or rank-sum test (reported as median (IQR)), and statistically adjusted for surgical center, age, sex, race, genetic anomaly, and pre-operative support with multivariate logistic regression (reported as adjusted odds-ratio (95% CI)).

Results:
Of 7,897 patients who underwent Fontan at 50 PHIS centers, 1,366 (17%) met criteria for H/SA. Patients with H/SA versus non-H/SA were older (3.7 (2.9-4.8) vs 3.4 (2.7-4.2) years; p<0.001), more female (44 vs 40%, p=0.005), and Asian or Hispanic (35% vs 24%, p<0.001). H/SA had higher rates of discharge death/transplantation (1.9 vs 1.1%, aOR 1.76 (1.02-3.04); p=0.042), post-operative ECMO (3.7 vs 2.3%, aOR 1.73 (1.28-2.33); p<0.001), dialysis (2.1 vs 1.2%, aOR 1.66 (1.06-2.59); p=0.026), prolonged intubation (13.2% vs 7.6%, aOR 1.86 (1.53-2.25); p<0.001), and longer LOS (11 (8-17) vs 9 (7-13) days; p<0.001).

Conclusions:
We observed increased mortality and postoperative complications in this largest report to date on patients with H/SA after Fontan. We postulate that ciliary dysfunction may contribute to increased lung and renal morbidity, and should be explored further. Adjustment for anatomic complexity and hemodynamics are required for further study
.
Abstract 15411: Healthy Aging Reduces Stroke Volume but Not Longitudinal Pumping at Rest or During Exercise
Authors: Tayon Kevin G , Macnamara James P , Cornwell William K , Howden Erin , Hieda Michinari , Lawley JUstin , LEVINE Benjamin D , Sarma Satyam
Published: November 2020

Background:
Healthy sedentary aging is accompanied by cardiac atrophy and decreases in left ventricular (LV) size, but its effects on longitudinal motion are unclear. Longitudinal pumping, generated by descent of the mitral annulus, efficiently contributes to the LV stroke volume (SV). This study aimed to determine the relative contribution of longitudinal motion to stroke volume at rest and exercise in healthy young and senior adults.

Methods:
Cardiopulmonary exercise testing with concurrent 3D echocardiography was performed in 22 subjects free of cardiovascular disease (Young n=12, age 32±2 years, Senior n=10, age 70±4 years) at rest and during submaximal exercise at a targeted heart rate of 100 bpm (Young 104±35 watts, Senior 83±36 watts, p = 0.18). Mitral annular excursion (MAE) and LV SV were measured using multi-beat 3D echo acquisition at rest and during sub-maximal exercise. MAE volume (MAEV) was measured by multiplying MAE by short axis area at the base of the LV. Relative longitudinal pumping was measured by dividing the MAEV and SV (%).

Results:
MAE and MAEV were similar between the young and senior groups at rest (Figure) and both increased with exercise (MAE Young: Δ4.0mm vs Δ Senior 3.3 mm, group x exercise p = 0.459, MAEV Young: 10.2 ml vs Δ Senior 7.1 ml, group x exercise p = 0.280). SV was lower in the senior group at both rest and exercise (group p = 0.024, group x exercise p = 0.029). While the relative contribution of longitudinal pumping to stroke volume during rest was higher in the senior group (group p = 0.013), there was no differential change with exercise (Young: Δ7.6% vs Senior Δ 7.9%, group x exercise p = 0.938).

Conclusions:
With sedentary aging, mitral annular excursion volume, a novel measure of systolic function, remains unchanged and results in higher relative contribution to a diminished stroke volume. Yet, the response to exercise is identical across the age groups, suggesting that efficient longitudinal contraction is preserved despite cardiac atrophy.
Abstract 15415: Trends and Predictors of Cardiogenic Shock and Mortality in Takotsubo Syndrome
Authors: Syed Moinuddin , KHAN Muhammad Z , Balla Sudarshan
Published: November 2020

Introduction:
There is limited data on trends, predictors and outcomes of cardiogenic shock (CS) and mortality among patients admitted with takotsubo syndrome (TTS). We aim to study these parameters from the national inpatient sample.

Methods:
We analyzed the National Inpatient Sample (NIS) database from September 2006 to December 2017 to assess the trends and predictors of cardiogenic shock and mortality among patients with TTS.

Results:
A total of total of 265,423 patients with takotsubo syndrome (TTS) were included in our study, of whom 14703 (5.5%) were diagnosed with cardiogenic shock (CS). TTS Patients with CS were more likely to be younger (67, Interquartile range [IQR] 57-75 vs 68, 58-78), males (20.9% vs 13.8%, P <0.01), with key ethnicities being Asian and Hispanic. TTS patients with CS were also more likely to have multiple medical comorbidities at baseline including congestive heart failure (65.7% vs 40.9%, P <0.01), chronic lung disease (31.1% vs 29.2%, P <0.01) diabetes with chronic complications (7.4% vs 5.6%, P <0.01) and chronic kidney disease (13.2% vs 11.1% P <0.01). TTS patients with CS had a higher incidence of malignant arrhythmias including ventricular tachycardia or ventricular fibrillation (15.0% vs 4.6%, P <0.01) and non-shockable cardiac arrests (12.2% vs 2.3%, P <0.01). In-hospital mortality among patients with TTS-CS was fivefold higher compared to those without CS (22.9% vs 4%, P <0.01). During our study period we also noted a significant increase in trends of cardiogenic shock and mortality among patients with TTS.

Conclusions:
In hospital mortality among TTS patients with CS was approximately five-fold higher compared to those without CS (22.9% vs 4.0%, P <0.01).Future research should be directed towards management strategies to improve outcomes in patients with TTS.
Abstract 15421: Effect of Sex and Age-group on Pulmonary Artery to Aorta Ratio in Healthy Aging: The Framingham Heart Study
Authors: Mohmand Mawa , Gona Philimon N , Salton Carol J , Tsao Connie W , O'Donnell Christopher J , Manning Warren J , Chuang Michael L
Published: November 2020

Introduction:
An increased ratio of main pulmonary artery (MPA) to ascending aorta (AAo) diameters is associated with excess morbidity and mortality in COPD and pulmonary hypertension. We sought to determine: 1) whether MPA to AAo ratio (MPA:AAo) varies with sex and age in healthy adults; 2) normal upper 90
th
percentile (P90) values for MPA:AAo; 3) effect of age on MPA:AAo in the general population.

Methods:
1794 adults from the Framingham Heart Study Offspring cohort (65±9 y, 47% men) underwent ECG-gated T2-weighted black blood aortic CMR at 1.5T. MPA and AAo diameters were measured at MPA bifurcation level or the adjacent slice. A referent group free of hypertension, LV focal wall motion abnormality, any history of smoking, asthma, COPD, DVT and obesity was identified and stratified by sex and age group (<55, 55-64, 65-74, ≥75 y). Data are summarized as mean±SD. P90 values were determined from referent participants. We tested for sex differences by 2-sample t test and for within-sex trend across age groups using linear regression.

Results:
Of the 1794 Offspring, 370 met referent group criteria, among whom men had greater MPA (23.4±2.9 vs 21.3±3.1 mm, p<0.0001) and AAo (31.1±2.9 vs 28.5±3.1 mm, p< 0.0001) diameters than women, but height-indexed AAo/HT (p=0.60) and MPA/HT (p=0.33) were not different between sexes. MPA:AAo did not differ between sexes, men=0.76±0.10, women: 0.75±0.15, p=0.97. P90 values for MPA:AAo were 0.88 (men) and 0.87 (women). MPA:AAo significantly decreased with age in both sexes (see Table) due to increasing AAo; MPA did not vary with age. In the overall population MPA:AAo also decreased with greater age, but here both AAo and MPA tended to increase with advancing age.

Conclusions:
Among healthy adults free of hypertension, obesity, and common pulmonary risk factors, MPA:AAo ratio does not differ between sexes. In healthy aging MPA:AAo decreases with age in both sexes, due to increased AAo diameters. These patterns are consistent in the general population.
Abstract 15424: Tricuspid Valve Geometry and Right Heart Remodeling: Insights Into the Mechanism of Atrial Functional Tricuspid Regurgitation
Authors: Utsunomiya Hiroto , Harada Yu , susawa hitoshi , Ueda Yusuke , Izumi Kanako , Itakura Kiho , Hidaka Takayuki , Shiota Takahiro , Nakano Yukiko , Kihara Yasuki
Published: November 2020

Introduction:
Functional tricuspid regurgitation (TR) caused by chronic atrial fibrillation with structurally normal tricuspid valve (TV) leaflets, normal right ventricular (RV) function, and dilated right atrium (RA), is considered as a new clinical entity, atrial functional TR (AF-TR). We sought to investigate TV geometry and right heart remodeling in AF-TR compared with ventricular functional TR with sinus rhythm (VF-TR).

Methods:
Transesophageal 3D echocardiography datasets of the TV and the RV were acquired in 51 symptomatic severe TR. 3D RV endocardial surfaces were reconstructed throughout the cardiac cycle and then postprocessed using semiautomated integration and segmentation software to calculate position of papillary muscle (PM) tips (Figure).

Results:
Compared with VF-TR, AF-TR had more dilated and posteriorly displaced annulus and less leaflet tethering angles with more prominent right atrium and smaller RV end-systolic volume. On the XY (annular) plane, the center of annulus was getting closer towards the anterior and posterior PM tips and was going away from the medial PM tip caused by prominent annular dilatation in AF-TR. On the Z axis, the position of each PM tip in AF-TR was not so much displaced apically as that in VF-TR. Multiple linear regression analyses revealed that right atrial volume and right atrial/RV end-systolic volume ratio were determinants of annular area and orientation in AF-TR, respectively (both
P
<0.001). Additionally, the posteromedial directed component of posterior PM tip position and the apically directed component of the position of all 3 PM tips were independently associated with TV tethering angles of each leaflet in AF-TR (all
P
<0.02). In subgroup analysis, massive to torrential AF-TR had a larger RV volume with more apically displaced PM tips than severe AF-TR.

Conclusion:
Right heart remodeling and its association with TV geometry differ between AF-TR and VF-TR, which offers distinctive therapeutic implications.
Abstract 15433: The Left Atrium and Pulmonary Vascular Disease in PVDOMICS Cohorts
Authors: Horn Evelyn M , Larive Brett , Rosenzweig Erika , Frantz Robert , Hassoun Paul , Hemnes Anna R , Rischard Franz , Finet Emanuel , Leopold Jane A ,   PVDOMICS Study Group
Published: November 2020

Left atrial (LA) size and function is recognized as a cumulative index of pulmonary capillary wedge pressure (PCWP) and an index of left heart disease (LHD). While anticipated that LA features contribute to LHD-associated pulmonary hypertension (PH), we hypothesized that LA abnormalities (LAA) may exist in other WSPH groups. Therefore, we examined LA structure and function in the PVDOMICS cohorts. PVDOMICS enrolled 1097 total subjects with PH (mPA
>
25 mmHg) and at-risk disease comparators (mPA<25 mmHg) for each of the WSPH groups. Patients with WSPH Groups 1, 3, 4, and 5 [non-Group 2] (n=618) were younger (56.2 ± 14.5 vs 60.1 ± 12.7 yrs, p<.02) and had less hypertension (38.6% vs 51.5 %, p<.02) than their non-Group 2 comparators (n=204). They also had less hypertension, diabetes, and a lower BMI than WSPH Group 2 (n=145), whereas WSPH Group 2 and its comparator Group 2 (n=130) were similar. LA area by echo was greater in WSPH Group 2 compared to non-Group 2 (22.8 ± 6.6 vs 16.9 ± 5.0 cm
2
, p<.02), in the comparator Group 2 vs. non-Group 2 comparators (22.7 ± 7.9 vs 16.4 ± 4.7 cm
2
, p<.02) but similar between WSPH group 2 and its comparator. MRI LA ejection fraction was lowest in Group 2 (33.2 ± 17.7%) and comparator Group 2 (38.9 ±16.7%, p=ns), significantly lower than WSPH non-Group 2 (45.9 ±14.7%, p<.02) which was lower than comparator non-Group 2 (50.9 14.6%, p<.02) which was lower than normal controls (n=96) (58.4 ±1.7%, p<.02). At right heart catheterization, whereas mPA pressures were similar between WSPH non-Group 2 and Group 2, resting PCW (11.1± 5.3 vs 20.3 5.6 mm Hg, p<0.02) was lower in WSPH non-Group 2 , PVR was higher (5.5[3.3, 8.7] vs. 3.7[7.2, 5.7] WU, p<0.02), and cardiac output was higher (5.4 ± 1.9 vs. 4.9 ± 1.6 L/min, p<0.02). Following a fluid challenge, PCW remained lower (14.9 ± 5.8 vs 20.7 ± 4.5 mm Hg, p<0.02) and PVR higher (5.2[3.1, 7.8] vs. 3.2[2.3, 5.5] WU, p<0.02). PCW and PVR at rest were lower in the comparator non-Group 2 vs WSPH non-Group 2 (8.9 ± 4.1 vs 11.1± 5.3 mm Hg, p<.02) and 1.7[1.2, 2.3] vs 5.5[3.3, 8.7] WU, p<.02. Thus, while LAA are most notable in WSPH and comparator Group 2’s, LAA differ between WSPH non-Group 2 and its non-Group 2 comparators. The role of LAA as predictors of PH outcomes remains to be determined.
Abstract 15436: Left Ventricular Ejection Fraction and MACE in Women With Signs and Symptoms of Ischemia: Data From the WISE (Women's Ischemia Syndrome Evaluation)
Authors: Wu Stephanie , Lauzon Marie , Maughan Jenna , Shaw Leslee J , Kelsey Sheryl F , Anderson R David D , Pepine Carl , Bairey Merz C Noel
Published: November 2020

Background:
Relatively high left ventricular ejection fraction (EF) (>65%) in women was recently associated with higher all-cause mortality over 6 years follow-up in the CONFIRM study. We sought to evaluate high EF and major adverse cardiovascular events (MACE) in the Women’s Ischemia Syndrome Evaluation (WISE) study.

Methods:
The WISE original cohort (enrolled 1996-2000) is a multicenter prospective study of women with suspected ischemic heart disease undergoing clinically indicated invasive coronary angiography. We investigated the relationship between high (>65%) and normal (55-65%) EF and MACE, defined as all-cause death, nonfatal myocardial infarction (MI), stroke and heart failure (HF) hospitalization using Kaplan Meier (KM) and regression analyses.

Results:
A total of 653 women were included (298 high and 355 normal EF). Mean age was 58±11 years and mean EF was 68±7%. There was no significant difference in MACE by EF group over a 10-year follow-up period (log rank p=0.54,
Figure
). When patients were stratified by the presence of obstructive CAD, MACE rates remained similar between high and normal EF. High EF was not associated with stroke or HF but had a lower MI risk (log rank p=0.03,
Table
). EF was not associated with MACE in a multivariable regression model.

Conclusions:
Among women presenting with evidence of ischemia, there was no significant difference in MACE between high and normal EF groups. High EF was associated with a lower risk of myocardial infarction as an individual component of MACE.
Abstract 15441: Determining the Optimal Thresholds for Classifying Functional Mitral Regurgitation Severity by Cardiac Magnetic Resonance Imaging in Patients With Non-ischemic Cardiomyopathy
Authors: Wang Tom Kai Ming , Choi Harry , Kocyigit Duygu , Milinovich Alex , Jin Jian , Popovic Zoran B , Tang Wai Hong W , Kapadia Samir R , Griffin Brian P , Flamm Scott D , Kwon Deborah H
Published: November 2020

Background:
Functional mitral regurgitation (MR) grading by echocardiography is often challenging, and cardiac magnetic resonance (CMR) may provide more accurate and reproducible assessment, however optimal CMR thresholds have not been established. We aimed to determine clinically significant thresholds of MR-volume and MR-fraction by CMR in patients with non-ischemic cardiomyopathy (NICM).

Methods:
All patients having CMR with confirmed NICM between 2001/4/1-2019/3/31 were retrospectively studied. Time to death, heart transplant and/or left ventricular assist device is the primary endpoint, and receiver-operative (ROC) characteristics analyses were used to identify significant cut-points for MR-volume and MR-fraction.

Results:
Mean MR-volume was 11±12% and MR-fraction 14±13% in 840 NICM patients. C-statistics for the primary endpoint (141 events) were MR-volume 0.629 (95%CI: 0.577-0.691) and MR-fraction 0.594 (95%CI 0.542-0.647). Thresholds of MR-volume≥10mL and MR-fraction≥15% had the highest products of sensitivities and specificities (57.4%, 56.8%; and 54.6%, 63.4% respectively) reflecting elevated risk. MR-volume≥35mL and MR-fraction≥40% were associated the best combination of positive and negative predictive values (40.1%, 84.2%; and 38.4%, 84.6% respectively) representing severe risk. The figure illustrates Kaplan-Meier curves of the primary endpoint, categorized into three subgroups based on aforementioned MR-volume and MR-fraction thresholds.

Conclusion:
Adverse prognosis are observed when MR-volume≥10mL or MR-fraction≥15%, with increasing risk of adverse outcomes as functional MR severity increased in NICM. The proposed MR thresholds from this study for elevated and severe risk are lower than current valvular regurgitation guidelines, suggesting the need for separate classification schema for functional MR.
Abstract 15442: Low Serum Levels of Insulin-like Growth Factor-1 Are Associated With Long-term Risk of Adverse Cardiovascular Events in Diabetic Patients Following Percutaneous Coronary Intervention
Authors: Chikata Yuichi , Iwata Hiroshi , Funamizu Takehiro , Miyosawa Katsutoshi , Doi Shinichiro , Endo Hirohisa , Wada Hideki , Naito Ryo , KONISHI Hirokazu , Ogita Manabu , Kato Yoshiteru , Okai Iwao , Dohi Tomotaka , Kasai Takatoshi , Isoda Kikuo , Okazaki Shinya , MIYAUCHI Katsumi
Published: November 2020

Background:
Insulin-like growth factor-1 (IGF-1) is a protein which plays protective roles against cardiovascular disorders, including the endothelial dysfunction and the instability of atherosclerotic plaque. However, prognostic implication of serum IGF-1 level has been rarely evaluated in diabetic patients with established coronary artery disease.

Methods:
This single center observational study involved consecutive 819 diabetic patients underwent percutaneous coronary intervention (PCI) since 2008 to 2018. In frozen-stocked (-80°C) serum, IGF-1 was measured by ELISA assay. Endpoints were set as cardiovascular (CV) death and the composite of CV death, myocardial infarction and ischemic stroke (3-point MACE). The median and the range of follow-up period was 4.0 and 0-10.4 years, respectively.

Results:
Participants were divided by the median of IGF-1 (75 ng/ml) (low (n=412) and high IGF-1 group (n=407)). Unadjusted Kaplan-Meier analyses with log-rank test showed the significantly higher incidences of CV death and 3P-MACE in low IGF-1 group (
Figures
). Moreover, multivariate Cox proportional hazard analysis adjusted by covariates including age, sex, PCI for acute coronary syndrome, multivessel disease, renal function (eGFR, ml/min/1.73m
2
) and glycated hemoglobin (HbA1c, %) demonstrated that low IGF-1≤75 ng/ml was associated with substantially increased risk of CV death (Hazard Ratio (HR): 1.9, 95% confidence interval (95%CI): 1.1-3.6, p=0.03) and 3P-MACE (HR 1.7, 95%CI:1.0-2.7, p=0.04), respectively.

Conclusion:
Findings in this study suggest that serum IGF-1 levels are a useful and independent prognostic indicator in diabetic patients following PCI.