bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14613: Preclinical Animal Model of Doxorubicin-induced Left Ventricular Dysfunction: Echocardiography and Pressure-volume Analysis
Authors: Kala Petr , Honetschlagerova Zuzana , Huskova Zuzana , Vanourkova Zdenka , Škaroupková Petra , Melenovsky Vojtech , Veselka Josef , Cervenka Ludek
Published: November 2020

Introduction:
There is a need to implement a preclinical model in addition to the well established ischemic or volume-overload models that would mimic the clinical course of patients with chemotherapy-induced heart failure. Doxorubicin is an anthracycline chemotherapeutic that is widely used in oncology, although its cardiotoxicity.

Hypothesis:
Doxorubicin-induced left ventricular dysfunction in rats fulfills echocardiography and hemodynamic characteristics of chemotherapy-induced heart failure.

Methods:
We randomly assigned Ren-2 transgenic hypertensive (TGR, n = 17) and normotensive rats (HanSD, n = 22), at the age of 8 weeks to doxorubicin (2.5 mg/kg in 0.5 ml of normal saline) or placebo in 6 intraperitoneal doses within two weeks (cumulative doxorubicin dose 15 mg/kg). Two weeks later, we performed echocardiography study, pressure-volume analysis (PV), and we weighed the organs.

Results:
In doxorubicin groups, there was a decrease in the left ventricle weight (1,22 vs. 0,85 g in TGR), while an increase in wall stress (22036 vs. 29754 μL*mmHg/g in TGR). Echocardiography suggested heart remodeling with a decrease in relative wall thickness - RWT (1.02 vs. 0.65 mm in TGR), and together with PV analysis showed a decrease in systolic parameters - left ventricle ejection fraction - LVEF (71.41 vs. 59.96 % in TGR), end-systolic pressure-volume ratio - ESPVR (0.82 vs. 0.45 mmHg/uL in TGR) and preload recruitable stroke work - PRSW (75.71 vs. 60.98 mmHg in TGR). Ventricular-arterial coupling (VAC = Ea/Ees, a measure of cardiac efficiency) was worsened in the doxorubicin groups (1.69 vs. 2.52 in TGR). For all the above p < 0.05, in HanSD, the results were similar (all p < 0.05).

Conclusions:
Our results suggest that systolic dysfunction and decrease of cardiac efficiency in this model could be caused by heart atrophy, and such an animal model could potentially be an easily reproducible model of chemotherapy-induced heart failure in preclinical cardio-oncology studies.
Abstract 14904: Alteration of Lipid Profile and Prognostic Value of Lipids on the Length of Hospital Stay in Covid-19 Pneumonia Patients
Authors: chen qin , Huang Minghan , luo yukun
Published: November 2020

Background:
The outbreak of the novel coronavirus SARSCoV-2 (coronavirus disease 2019; COVID-19) has spread to most of countries in the world. The tight relationship of plasma lipids and COVID-19 pneumonia (NCIP-19) has not been well invested. To observe lipid profiles and their alterations in hospitalized patients with COVID-19 and evaluated the prognostic value of lipids for the length of hospital stay (LOS).

Methods:
248 NCIP-19 cases aged 18 years or older were enrolled in this study. Serum lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected at admission. In 68 severe cases, levels of serum lipids were subsequently detected every 5 ~ 10 days.

Results:
At admission, median levels of TG, TC, HDL-C, and LDL-C in all patients, were 1.11 mmol/L, 4.00 mmol/L, 0.89 mmol/L and 2.11 mmol/L, respectively. Compared with common cases (n=174), higher TG and HDL-C, lower LDL-C were observed in severe cases (n=74). Levels of TC and LDL-C at admission were negatively correlated with LOS. In severe cases, the average levels of serum lipids were lowest at admission and gradually increased during hospitalization. Compared with the LOS≤29d group, serum levels of TC, HDL-C, and LDL-C were significantly lower in the LOS>29d group at admission; this lower trend always existed during the following tests for TC and LDL-C, but not for HDL-C and TG. Patients with LDL-C≥1.70 mmol/L at admission showed a lower risk of LOS prolongation (adjusted HR=0.557, 95% CI: 0.409-0.759,
p
<0.001).

Conclusions:
In NCIP-19, serum lipid levels were low at admission. Levels of TC and LDL-C at admission were negatively correlated with LOS. LDL-C <1.7 mmol/L at admission may act as the independent predictor of LOS prolongation. In severe cases, the gradual increase of TC, LDL-C, and HDL-C during the hospitalization might indicate the gradual recovery of the disease.
Abstract 14912: Sotalol-induced Wide Complex Rhythm: What is the Mechanism?
Authors: Rogers Albert J , Wang Paul J , Badhwar Nitish
Published: November 2020

Introduction:
Delta waves associated with atrioventricular accessory pathways (APs) may manifest with autonomic tone, heart rate, and rhythm changes. Rarely, drugs like sotalol can block AV nodal conduction, revealing latent WPW, one treatable cause of sudden death.

Case report:
A 38-year-old man was admitted for sotalol loading due to frequent typical atrial flutter and SVT and a desire to avoid catheter ablation. He had a history of cardiac arrest with adenosine and tachycardia-induced cardiomyopathy. After recovery, cardiac MRI showed a normal heart without scar. Admission 12-lead ECG (
Figure A
) revealed normal sinus rhythm without other abnormality. With administration of sotalol, the patient developed a wide complex rhythm (
Figure B
). Interpretation of the rhythm indicated presence of a latent AP and a repeat ECG (
Figure C
) confirmed manifest preexcitation. After consenting to electrophysiology study, the patient developed a short RP tachycardia (
Figure D
) which terminated with Valsalva. The patient underwent successful catheter ablation of the pathway located at the anterior floor of the coronary sinus body and the cavotricuspid isthmus.

Discussion:
The differential diagnosis for a wide complex rhythm in this setting includes rate-related aberrancy, idioventricular rhythm, phase 4 aberrancy, and preexcitation from an AP. Shortened and consistent PR intervals in the tracing lead to preexcitation as the only possible mechanism. APs that are capable of anterograde conduction but are not manifest in sinus rhythm are termed latent APs. Conditions that may cause this phenomenon include opposite autonomic effects on the AP and the AV node, increased atrial conduction time, or concealed retrograde conduction into the AP. Sotalol typically increases the retrograde effective refractory period of the AP but has variable anterograde effect. Sotalol has not previously been reported to reveal a latent AP but may have acted through one of the stated mechanisms.
Abstract 14914: Advanced 4D-flow Measurements of Aortic Forward Flow, Reverse Flow, and Stasis in Bicuspid Aortic Valve Patients Without Aortic Stenosis or Regurgitation
Authors: Geeraert Patrick , jamalidinan Fatemehsadat , Fatehi Hassanabad Ali , White James , Garcia Flores Julio
Published: November 2020

Introduction:
Precise analysis of aortic hemodynamics is crucial in the study of bicuspid aortic valve (BAV) disease. This study provides a comprehensive evaluation of aortic forward flow (FF), reverse flow (RF) and stasis in BAV patients using novel 3D-based techniques previously shown to be more accurate than traditional 2D analysis methods.

Hypothesis:
BAV patients without valve dysfunction show abnormal aortic FF, RF, and stasis compared to healthy controls.

Methods:
We recruited 44 BAV patients (48±15 yrs, 27% female) and 23 healthy controls (37±14 yrs, 35% female). Cardiac MRI at 3T was performed inclusive of 4D-flow imaging. Patients with any aortic stenosis (AS) or ≥mild regurgitation (AR) were excluded. Flow analysis was performed by segmented volumetric regions: left ventricular outflow tract (LVOT), ascending aorta (AAo), arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region, forward flow (FF), reverse flow (RF) and stasis were averaged over the cardiac cycle on a voxel-by-voxel basis. Left ventricular (LV) end-diastolic volume, end-systolic volume and ejection fraction were also measured. T-tests (or non-parametric equivalent) compared differences in parameters between cohorts.

Results:
BAV patients were significantly older than controls (48±15 vs. 37±14 yrs; p=0.01) but exhibited no significant differences in LV measures. Patients showed reduced FF in the AAo (0.09±0.03 vs. 0.11±0.04 mL/cycle; p<0.01), but greater FF in all downstream regions (eg. PDA: 0.02±0.03 vs. 0.01±0.02 mL/cycle; p=0.01). RF was significantly elevated in patients in the AAo (0.06±0.02 vs. 0.02±0.02 mL/cycle; p<0.01). BAV patients exhibited significantly less stasis in every region except the DDAo (eg. AAo: 23±11 vs. 50±10 % of cardiac cycle).

Conclusions:
3D-derived measurements of FF, RF, and stasis are significantly altered in the thoracic aorta of BAV patients in the absence of AS or AR.
Abstract 14920: Predictors of Adverse Outcomes Following Elective Ascending Aortic Aneurysm Repair: A Nationwide Cohort Study
Authors: Beyer Sebastian E , Khabbaz Kamal R , Schmaier Alec , Secemsky Eric A , Carroll Brett
Published: November 2020

Introduction:
Elective surgical intervention for ascending aortic aneurysm (AA) is performed when the risk of a future aortic catastrophe outweighs the risk of surgery; however, the data of complication rates following elective repair are limited.

Methods:
We analyzed adults >18 years of age hospitalized for elective ascending AA surgical intervention in the 2016 and 2017 Nationwide Readmissions Databases. The primary outcome was in-hospital mortality. Secondary outcomes were acute ischemic stroke (AIS), acute myocardial infarction (AMI) and non-elective 30-day readmission. Bayesian lasso probit regression models were used to identify independent predictors of primary and secondary outcomes.

Results:
Among 4,073 patients hospitalized for elective surgical repair, 28.9% were female. Mean age was 63.0 ± 12.4 years. Concomitant aortic valve surgery was performed in 67%. Overall, 72 (1.8%) died during the initial hospitalization (Figure A). Predictors of in-hospital mortality are shown in Figure B. Of patients alive at discharge, 482 (11.8%) were readmitted within 30 days, with a mortality rate of 2.3% during readmission. Predictors of non-elective 30-day readmission included non-urban localization (Change in probability: 32.5%, 21.7 - 45.7%), chronic liver disease (18.1%, 11.4 - 27.0%), and chronic neurological disorder (15.9%, 12.1 - 20.1%). Main causes of readmissions were arrythmias (20.3%), procedural complications (14.5%), and peri-, endo-, or myocarditis (9.3%). While procedural volume varied between one and 68 procedures / institution, it was not associated with in-hospital mortality, AIS, AMI, or 30-day readmission (p>0.05 for all).

Conclusions:
One in 25 patients will have a significant complication or die following elective ascending aortic repair and 1 in 8 will be readmitted within 30 days. The risk of surgery compared to the risk of a future aortic catastrophe should be thoroughly assessed prior to recommendation of an ascending AA repair.
Abstract 14925: Mechanical Tension in Syndecan-1 is Regulated by Extracellular Mechanical Cues and Fluidic Shear Stress
Authors: Mei Lei , Le Victoria , Voyvodic Peter , Zhao Chi , Busch David , Stachowiak Jeanne , Baker Aaron
Published: November 2020

Syndecan-1 (SDC1) is a transmembrane proteoglycan that mediates the shear stress-induced signaling and inflammatory phenotypes of endothelial cells. While SDC1 is known to be involved mechanically in regulating the behavior of cells, it remains unknown how SDC1 responds to extracellular mechanical cues on the molecular level. We designed a set of FRET-based SDC1 tension sensors including full-length SDC1 (SDC1TS), SDC1 with deleted ectodomain (ΔEcto), SDC1 with deleted glycosylation sites (ΔGAG) and SDC1 with a deleted cytoplasmic tail (ΔCyto). We transduced these constructs into ECs and validated the constructs by WB and confocal imaging. When cultured on glass-bottom coverslips, we found that the baseline tension in SDC1TS was significantly higher than that in Ecto and GAG mutants. When cultured on engineered substrates, we demonstrated that tension in SDC1 is modulated by micropatterned surfaces and nanotopographical cues. To study if SDC1 directly responds to substrate stiffness, transduced ECs were cultured on 0.2 kPa and 25 kPa substrates. We found that there was significantly decreased tension in the Ecto construct compared to the full-length SDC1TS construct on 0.2 kPa substrates but no significant changes were observed on the 25 kPa substrates. To examine the effect of substrate stiffness on the association of SDC1 with adhesion-related proteins, we performed IP and WB on ECs expressing HA-tagged SDC1 cultured on 0.2 kPa or 25 kPa substrates. We found there were increases in SDC1 binding to action and myosin IIb, while there were decreased in SDC1 binding to Src, PKA, and FAK in cells grown on stiff substrates versus on soft substrate. To study the effect of shear stress on the tension of SDC1, ECs expressing the constructs were cultured on static or under 12dyn/cm
2
fluidic shear stress. We found that a gradient developed in the tension of SDC1 in all four constructs. There was higher tension of SDC1 in the upstream region in comparison to the downstream region. IP and WB results showed that shear stress-induced SDC1 association with actin, Src, myosin IIb, cortactin, calmodulin, and integrin beta3. In summary, our results demonstrate that SDC1 is mechanically responsive to substrate mediated biophysical cues and shear stress.
Abstract 14943: Comparison of Heart Failure Patients Newly Prescribed Sacubitril/valsartan With Those Newly Prescribed Aceis/arbs; A Cohort Study Using Us Optum Electronic Health Record Data
Authors: Loefroth Emil , Shen Xian , Studer Rachel , Schlienger Raymond , Proudfoot Clare , Corda Stefano , Saha Sibasish , Satwase Sarvesh K , Houchen Emma
Published: November 2020

Background:
The clinical development program of sacubitril/valsartan (sac/val) for heart failure with reduced ejection fraction (HFrEF) only included a very limited number of patients being naive to prior angiotensin converting enzyme inhibitors (ACEis) or angiotensin II receptor antagonists (ARBs). Recent studies support the use of sac/val in hospitalised HF patients without prior ACEis/ARBs. This study aims to compare HF patients newly prescribed either sac/val or ACEis/ARBs.

Methods:
Retrospective non-interventional cohort study describing two mutually exclusive adult patient cohorts diagnosed with HFrEF either initiating sac/val or ACEis/ARBs. All patients were naive to both sac/val and ACEis/ARBs for 12 months prior to the first prescription. All patients had a left ventricular ejection fraction (LVEF) ≤40%. Patients were identified any time between 1
st
July 2015 and 31
st
Dec 2018 in the Optum® de-identified EHR dataset from providers across the continuum of care.

Results:
2,414 patients were initiated on sac/val, 36,563 on ACEis/ARBs. Mean age was 66.1 (SD 12.9) and 67.2 years (SD 13.7) for sac/val and ACEis/ARBs users, respectively. Sac/val patients were more likely to be male: 70.8% vs 67.2% (p<0.0001) and had a lower mean LVEF: 26.9% vs 29.3% (p<0.0001). Patients newly initiated on sac/val had similar proportion of ischemic heart disease (67.9% vs 68.2%, p=0.72), and more often valvular heart disease (48.6% vs 44.3%, p<0.0001), and use of cardio resynchronization therapy device (40.9% vs 24.0%, p<0.0001).

Conclusions:
This real-world study indicates that sac/val tends to be newly prescribed to younger, male HFrEF patients with lower LVEF and a higher proportion of cardio resynchronization therapy devices compared with patients newly initiated on ACEis/ARBs. The prevalence of ischemic heart disease is similar between the groups.
Abstract 14955: Machine Learning Predicts Hemodynamic Instability in Children After Cardiac Surgery in Pediatric Intensive Care Unit (PICU)
Authors: Sughimoto Koichi , Levman Jacob , Baig Fazleem , Berger Derek , Oshima Yoshihiro , Kurosawa Hiroshi , Aoki Kazunori , Seino Yusuke , Ueda Tetsuya , Liu Hao , Miyaji Kagami
Published: November 2020

Introduction:
Despite improvements in management for children after cardiac surgery, a non-negligible proportion of patients suffer from cardiac arrest, having a poor prognosis. Although serum lactate levels are widely accepted markers of hemodynamic instability, measuring lactate requires discrete blood sampling. An alternative method to evaluate hemodynamic stability/instability continuously and non-invasively may assist in improving the standard of patient care.

Hypothesis:
We hypothesize that blood lactate in PICU patients can be predicted using machine learning applied to arterial waveforms and perioperative characteristics.

Methods:
Forty-eight children, who underwent heart surgery, were included. Patient characteristics and physiological measurements were acquired and analyzed using specialized software/hardware, including heart rate, lactate level, arterial waveform sharpness, and area under the curve. Predicting a patient’s blood lactate levels was accomplished using regression-based supervised learning algorithms, including regression decision trees, tuned decision trees, random forest regressor, tuned random forest, AdaBoost regressor, and hypertuned AdaBoost. All algorithms were compared with hold-out cross validation. Two approaches were considered: basing prediction on the currently acquired physiological measurements along with those acquired at admission, as well as adding the most recent lactate measurement and the time since that measurement as prediction parameters. The second approach supports updating the learning system’s predictive capacity whenever a patient has a new ground truth blood lactate reading acquired.

Results:
In both approaches, the best performing machine learning method was the tuned random forest, which yielded a mean absolute error of 5.60 mg/dL in the first approach, and 4.62 mg/dL when predicting blood lactate with updated ground truth.

Conclusions:
In conclusion, the tuned random forest is capable of predicting the level of serum lactate by analyzing perioperative variables, including the arterial pressure waveform. Machine learning can predict the patient’s hemodynamics non-invasively, continuously, and with accuracy that may demonstrate clinical utility.
Abstract 14956: Improved Operative Efficiency for Minimally Invasive Mitral Valve Surgery at a Low-volume Center
Authors: Fowler Monica , MacLeod Jeffrey B , aguiar christie , Yip Alexandra M , pozeg zlatko , Brown Craig D , Légaré Jean-François , Hassan Ansar
Published: November 2020

Introduction:
When implementing a minimally invasive cardiac surgery program, increased surgical times may serve as a deterrent. Results demonstrating parity in operative times between minimally invasive (MIMVR) and conventional mitral valve replacement/repair (CMVR) have been limited to high-volume centers. The purpose of this study was to examine operative efficiency for MIMVR in a low-volume center.

Methods:
All patients having undergone non-emergent, isolated MIMVR or CMVR at the New Brunswick Heart Centre from 2011-2017 were considered. Detailed peri-operative data, including cross clamp (XC), cardiopulmonary bypass (CPB), skin-to-skin (SS) and total operative (TO) times, were collected. Patients were assigned to one of 3 eras: 2011-2013, 2014-2015, 2016-2017. Unadjusted comparisons were made between MIMVR and CMVR over the entire study period and within each era.

Results:
A total of 168 patients were included (MIMVR: 64; CMVR: 104). There was an increase in the number of MIMVR cases over time (2011-2013: 19; 2014-2015: 17; 2016-2017: 28). Patients undergoing MIMVR were less likely to be ≥70years (29.7% vs. 47.1%, p=0.04) and to have had NYHA-IV symptoms (17.2% vs. 41.3%, p=0.002), previous cardiac surgery (4.7% vs. 23.1%, p=0.003) or urgent presentation (12.5% vs. 35.6%, p=0.002). Intra-operatively, MIMVR patients were more likely to have undergone a mitral valve repair (65.1% vs. 29.1%, p<0.0001). No differences were noted in rates of in-hospital mortality (0.0% vs. 5.1%, p=0.29). Median operative times were uniformly longer among MIMVR patients between 2011-2013. However, in 2014-2015 and 2016-2017, these times improved to the point where no significant differences in operative efficiency were noted (Figure).

Conclusions:
Improved operative efficiency may be safely achieved for MIMVR in a low-volume center. The results of this study should encourage low-volume centers to adopt a minimally invasive approach to isolated mitral valve surgery.
Abstract 14960: Empagliflozin Reduces the Total Burden of Cardiovascular Events Including Recurrent Events in the EMPA-REG OUTCOME Trial
Authors: Fitchett David H , Inzucchi Silvio E , Zinman Bernard , Wanner Christoph , Anker Stefan D , Pocock Stuart , Kaspers Stefan , George Jyothis T , Johansen Odd Erik , Jamal Waheed , Hantel Stefan , Lund Søren S
Published: November 2020

Introduction:
In EMPA-REG OUTCOME, empagliflozin (EMPA) reduced the risk of major adverse cardiovascular (CV) events (MACE), CV mortality and hospitalization for heart failure (HHF) in analyses of first events in patients with type 2 diabetes (T2D) and atherosclerotic CV disease (ASCVD). We assessed the effect of EMPA on the total burden of CV events.

Methods:
Patients were randomized to EMPA 10 mg, EMPA 25 mg, or placebo. We assessed the effects of EMPA pooled vs placebo on any (first plus recurrent) adjudicated CV event (composite of myocardial infarction (MI), stroke, coronary revascularization (CR), hospitalization for unstable angina, transient ischemic attack, HHF, and CV death) using a negative binomial model.

Results:
Among 7,020 treated patients (mean [SD] age 63 [9] years), there were 2,142 total adjudicated CV events, most frequently CR (585), MI (421), and HHF (321). EMPA reduced the risk of total adjudicated CV events by 24% vs placebo (event rate ratio (95% CI): 0.76 (0.67, 0.87), p<0.0001) (Figure). Risk reductions were driven predominantly by reductions in HHF (0.58 (0.42, 0.81), p=0.0012), MI (0.79 (0.620, 0.998), p=0.0486), and CV death (0.62 (0.49, 0.77), p<0.0001). The estimated number of total CV events prevented with EMPA was 414.4, and the number of patients needed to treat over 3 years to prevent one event was 10.2 (6.6, 22.7).

Conclusions:
EMPA produced a sizeable risk reduction in the total burden of any adjudicated CV outcome, including HHF, MI and CV death, in patients with T2D and ASCVD.
Abstract 14963: Accelerometer-measured Activity in Non-obstructive Hypertrophic Cardiomyopathy: Patient-generated Activity Measures Correlate With, and Are Convolutional Neural Network Predictors of, Clinical Parameters in the MAVERICK-HCM Study
Authors: Agarwal Priyanka , Shcherbina Anna , Day Sharlene , Saberi Sara , Mealiffe Matthew E , Edelberg Jay M , Li Yunfan , Ashley Euan
Published: November 2020

Introduction:
Overall activity characteristics for patients with hypertrophic cardiomyopathy (HCM) have not been quantified previously. The relationship between physical activity quantified by accelerometry and biomarkers, exercise capacity, and quality of life in patients with HCM is also unknown.

Methods:
MAVERICK-HCM was a double-blind, placebo-controlled, 16-week study of mavacamten in 59 patients with symptomatic non-obstructive HCM. Patients were asked to wear ActiGraph GT9X Link wrist-worn monitors for ≥11 days between screening and day 1, and between weeks 12 and 16. Features derived from raw accelerometry data included average daily accelerometer units (ADAU) and step count. Univariate Pearson correlation coefficients were calculated between accelerometry data and clinical parameters among all patients. A multi-task convolutional neural network (CNN) was trained on raw accelerometry datapoints to jointly predict clinical markers of HCM severity. Test and training sets were derived by randomly segmenting each patient’s triaxial accelerometry data into non-overlapping minute intervals.

Results:
Fifty patients wore the accelerometer for ≥1 compliant day. Mean wear time was 12 days during screening and 10 days during treatment. Activity measures are summarized and average step count was 3,076 steps at baseline (
Table
). Activity features correlated with peak oxygen uptake (pVO
2
), log NT-proBNP, and KCCQ score (
Table
). CNN predictions of clinical measures from activity data found Spearman R correlations of 0.82 for pVO
2
, 0.92 for log NT-proBNP, 0.82 for KCCQ, and 0.79 for E/e’.

Conclusions:
HCM patients in the MAVERICK study averaged only 3,000 steps/day. Markers of physical activity drawn from accelerometry are associated with standard clinical markers of HCM severity. Deep learning models can be constructed to predict markers of HCM severity from patients’ raw accelerometry data.
Abstract 14967: Pregnancy Outcomes in Sickle Cell Disease With Elevated Right Ventricular Systolic Pressure - High Thromboembolic Risk
Authors: Marshall William H , Gee Stephen , Desai Payal , Bradley Elisa A , Daniels Curt , Benza Raymond L , Rajpal Saurabh
Published: November 2020

Introduction:
Pulmonary hypertension (PH) diagnosed by elevated right ventricular systolic pressure (RVSP) is present in 6-11% of patients with sickle cell disease (SCD) and is associated with increased mortality. PH, independent of SCD, is associated with increased maternal mortality. While there are reports of adverse outcomes during pregnancy in patients with SCD, pregnancy outcomes of patients with SCD and PH have not been well studied.

Methods:
Using our institutional electronic data warehouse we searched for pregnant women who had an echocardiogram between November 1, 2011 and April 30, 2018, and met criteria for pulmonary hypertension with report of either RVSP > 35 mmHg or tricuspid regurgitant (TR) velocity of more than 2.8 m/s. We assessed maternal and fetal outcomes in this group of patients.

Results:
We identified 136 women with elevated RVSP, of which 7 (5%) had SCD (mean maternal age 29 ± 3 years, mean RVSP 47 ± 11 mmHg, mean TR velocity 3.1 ± 0.4 m/s). RVSP was known to be elevated before pregnancy in 5 (71%). There were no maternal deaths during pregnancy or up to 1-year post-partum. Thromboembolic complications occurred in 3 (43%); including 1 deep vein thrombosis with presumed pulmonary embolism (PE) at 20 weeks gestational age (GA), 1 catheter associated right atrial thrombus at 22 weeks GA, and 1 PE at 16 weeks GA. There were no heart failure complications. Cesarean section occurred in 5 (71%), all for obstetric indications. There were no fetal or neonatal deaths. Pre-eclampsia occurred in 2 (28%). The average gestational age was 35 ± 4 weeks. Preterm birth and low birth weight occurred in 3 (43%) patients.

Conclusion:
In conclusion, there was no maternal mortality or heart failure in pregnant women with SCD and elevated RVSP at our high-volume center, however 3 of 7 patients (43%) had thromboembolic complications. Further studies of women with PH and SCD are needed to assess the thromboembolic risk during pregnancy.
Abstract 14971: Impact of Medicare Diagnosis Code Expansion and Inclusion of Outpatient Data on Risk-adjusted 30-day Mortality and Readmission Rates After Acute Myocardial Infarction
Authors: Gilstrap Lauren , Wadhera Rishi , Austin Andrea , Kearing Stephen A , Joynt Maddox Karen , Yeh Robert W
Published: November 2020

Introduction:
In January 2011, the Center for Medicare and Medicaid Services increased the number of billing codes allowed per admission from 9 to 25. This caused an artificial increase in comorbidity burdens. Some have argued including outpatient data mitigates this problem. The aim of this study was to explore the impact of diagnosis code expansion, using inpatient and inpatient+outpatient data and evaluate potential solutions for conducting longitudinal studies of 30-day risk-adjusted outcome rates after acute myocardial infarction (AMI).

Hypothesis:
Limiting diagnosis codes and including outpatient data would produce the most stable estimates of risk-adjusted outcomes over time.

Methods:
We used 100% Medicare data to create a cohort of beneficiaries with AMI between 2008 and 2013. We used 4 methods to calculate the hierarchical condition categories/patient (HCC/pt) necessary for risk adjustment: 1) inpatient-only data, limited codes after 2011; 2) inpatient-only data, unlimited codes; 3) inpatient+ outpatient data, limited codes; 4) inpatient+outpatient data, unlimited codes.

Results:
Using inpatient-only data, expanding diagnosis codes increased the average HCC/pt by +0.23 HCC/pt. Using inpatient+outpatient data, the average increase was only +0.11 HCC/pt. (relatively 109% less,
Figure A
). Between 2009-2013, AMI mortality was flat while readmissions declined (
Figure B
). For mortality, all 4 methods produced estimates that were, on average, +0.7% higher than unadjusted (raw) rates. For readmission, the closest to unadjusted and most stable over time was inpatient+outpatient data with limited codes.

Conclusion:
For studies that span January 2011, diagnosis codes should be limited to 9 after 2011 when using inpatient or combined inpatient and outpatient data.
Abstract 14975: Increased Morbidity and Mortality in Patients With Hypoplastic Left Heart Syndrome and Genetic Abnormalities
Authors: Pierick Alyson R , Pierick Trudy A , Reinking Benjamin E
Published: November 2020

Introduction:
Hypoplastic left heart syndrome (HLHS) is a genetically heterogenous, severe form of congenital heart disease.

Hypothesis:
Patients with reported genetic abnormalities will have worse outcomes than those without reported genetic abnormalities.

Methods:
This was a retrospective review of patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase I registry. Registry enrollment occurred at discharge following stage 1 palliation. Patients were placed into one of three groups: major syndromes (Turner, Down, CHARGE, DiGeorge, Jacobsen, VATER, heterotaxy), other genetic abnormality, or no reported genetic abnormality. Demographic and clinical variables were compared using Pearson Chi-square, one-way ANOVA, or Kruskal-Wallis test. Tukey post-hoc test was applied to adjust p-values for pairwise group comparisons. Outcomes of length of stay, death, and combined outcomes of death, not a candidate for stage 2 palliation and transplant were compared among the groups.

Results:
Of the 2182 patients, major syndromes were reported in 110 (5%), other genetic abnormalities in 126 (5.8%) and no abnormalities in 1946 (89.2%). Those with major syndromes weighed less at birth and the time of stage I palliation, were more likely to be female and have a primary cardiac diagnosis of unbalanced AVC. Those with major syndromes or other genetic abnormalities were more likely to have moderate to severe AV valve regurgitation, moderate to severe ventricular dysfunction, arrhythmia requiring therapy, and major anomalies of other organ systems compared to those with no abnormalities. Patients with no reported genetic abnormalities reached full oral feeds sooner after the Norwood (19 vs 24 days), were more likely to be discharged on all oral feeds (75% vs 59% and 62%) and were discharged earlier (35 vs 45 and 43 days). For the outcome of death, there was no significant difference among the groups. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more likely in those with a major syndrome after adjusting for covariates.

Conclusions:
Patients with HLHS and major syndromes or other genetic abnormalities experience greater morbidity and mortality during the interstage period.
Abstract 14982: Paravertebral Block With a Paravertebral Catheter May Improve Outcomes After Minimally-invasive Cardiac Surgery
Authors: Kim Diane , Hsieh Monica , Schisler Travis , Cook Richard
Published: November 2020

Background:
Postoperative (post-op) pain following minimally-invasive cardiac surgery (MICS) may complicate outcomes in patients having surgery performed through a right mini-thoracotomy. Regional anaesthesia, by delivery of local anaesthetic agents to the paravertebral space using a paravertebral catheter (paravertebral block, PVB) may be useful to reduce post-op pain, however, few studies have reported outcomes on patients undergoing MICS with the use of a PVB.

Methods:
Ninety consecutive patients who underwent MICS at Vancouver General Hospital between January 2016 and May 2019 were included in this retrospective study. Data were collected for 53 patients who only had routine pain control (control) and 37 patients who had a PVB (PVB). Primary outcomes were post-op opioid use and hospital length of stay (LOS). Peri-operative (peri-op) death and stroke were secondary outcomes. Statistical analyses were performed using ANOVA single factor and t-tests.

Results:
Patient demographics and operative times were comparable between the two groups. The average total amount of opioid consumed in the PVB group was lower at 155.3 mg morphine equivalents, compared to 193.9 mg in the control group, however, the difference was not statistically significant (p=0.39) (Figure 1). However, the percentage of patients who did NOT receive any oxycodone was almost double in the PVB group (43.2% vs 24.5%, PVB vs control, respectively. p=0.06). The average LOS for the PVB group was significantly lower than the control group (5.4 vs 8.3 days, PVB vs control, respectively. p=0.006) (Figure 1). There were no peri-op deaths or strokes.

Conclusion:
In our experience, addition of a regional anesthetic was associated with ~20% reduction in the amount of opioid narcotic required. Although not statistically significant, this may be a clinically important difference, as the LOS was significantly lower in the PVB group. Outcomes in patients undergoing MICS may be improved with the addition of a PVB.
Abstract 15006: Serotonin Transporter (SERT) Knockout Leads to Increased Myocardial and Mitral Valvular Fibrosis in a Murine Model
Authors: D'Angelo Alex , Castillero Estibaliz , LEVY Robert , Ferrari Giovanni
Published: November 2020

Introduction:
Heart valve disease attributed to serotonin (5HT) has been observed with 5HT-secreting carcinoid tumors and with the diet drug, Dexfenfluoramine, a 5HT transporter (SLC6A4, also known as SERT) inhibitor and 5HT receptor (HTR) 2B agonist. 5HT/SLC6A4 mechanisms had not been investigated in mitral valve (MV) regurgitation. SLC6A4 internalizes 5HT, limiting HTR signaling. Selective 5HT reuptake inhibitor (SSRI) antidepressants target SLC6A4 to increase 5HT. We showed that SLC6A4 reduction in human MV influences MV regurgitation through enhanced HTR signaling. We further investigate the cardiac impact of SLC6A4 deficiency in a SERT
-/-
mouse reported to have cardiac abnormalities.

Hypothesis:
Absence of SERT leads to increased myocardial and MV fibrosis.

Methods:
SERT
-/-
and wild type (WT) C57BL/6J mice underwent echocardiography at 8 and 16 weeks (w) of age (N=5 / group). Collagen staining was performed with Masson’s trichrome. Markers of myocardial fibrosis α-smooth muscle actin (αSMA) and collagen type1, alpha 1 (COL1A1) were measured by PCR.

Results:
8w and 16w SERT
-/-
mice showed increased epicardial fibrosis and MV sub-valvular fibrosis, particularly at leaflet attachment points, and in 16w SERT
-/-
mice MV leaflet fibrosis was also present. At 8w, posterior ventricular wall thickness was greater in SERT
-/-
mice vs. WT, both in systole (1.30 ± 0.09mm vs. 1.61 ± 0.2mm, p=0.003) and diastole (0.78 ± 0.11mm vs. 1.22 ± 0.29mm, p=0.001). At 16 w, ventricular dimensions were larger in SERT
-/-
mice vs. WT at end-systole (2.29 ± 0.54mm vs. 3.0 ± 0.47mm, p=0.008) and end-diastole (3.48 ± 0.45mm vs. 4.07 ± 0.35, p=0.006). Fractional shortening was reduced in 16w SERT
-/-
mice vs. WT (35.20 ± 7.66 vs. 26.74 ± 6.14, p=0.017) and vs. 8w SERT
-/-
mice (38.85 ± 4.57 vs. 26.74 ± 6.14, p=0.002). PCR showed increased fibrosis markers αSMA and COL1A1 in SERT
-/-
mice (8w and 16w) vs. WT (all p<0.05).

Conclusions:
SERT
-/-
mice show pathologic structural changes and fibrosis in both myocardium and MV, corresponding to functional differences that worsen with age. As inhibition of SLC6A4, combined with active HTR2A/B signaling would hypothetically increase MV remodeling and regurgitation, these animals could be ideal to test 5HT pharmacology.
Abstract 15010: Myocardial Injury in Sepsis With Acute Respiratory Distress Syndrome
Authors: Dugan Eunice S , Stephens Robert S , Schulman Steven P , Metkus Thomas S
Published: November 2020

Introduction:
Sepsis is common and associated with high morbidity and mortality; novel prognostic biomarkers are needed. The association of myocardial injury with mortality in sepsis has not been fully characterized.

Hypothesis:
We hypothesized that elevated plasma high-sensitivity troponin I (hs-TnI) would be associated with 60-day mortality in patients with sepsis and acute respiratory distress syndrome (ARDS).

Methods:
We conducted a retrospective multicenter cohort study of subjects from the MI-ARDS study with ARDS and sepsis. The exposure variable was plasma hs-TnI on intubation (Day 0) and Day 3. Hs-TnI was measured using Abbott Laboratories’ ARCHITECT STAT assay. Patients were divided into four hs-TnI (ng/L) groups (Grp): GrpA: <2 (undetectable), GrpB: ≥2-<26 (<99
th
percentile of population), GrpC: ≥26-<130 (<5 times upper limit of normal [ULN]), GrpD: ≥130 (>5 times ULN). The primary outcome was 60-day mortality. We determined the association between hs-TnI and mortality using Cox proportional hazards models.

Results:
Of 320 subjects, there were 15 (4%) in GrpA, 97 (30%) in GrpB, 88 (28%) in GrpC, and 120 (38%) in GrpD. Mean age was 50 years and 172 subjects (54%) required vasopressors. Higher plasma levels of hs-TnI were associated with higher SOFA score and creatinine, and more vasopressor use. Overall mortality was 33%. There was no significant difference in 60-day survival between clinical categories of Day 0 hs-TnI (Fig 1-A). Rising troponin between Day 0 and Day 3 was associated with a higher risk of mortality after adjusting for age, sex, trial assignment, and SOFA score (HR: 1.75, CI: 1.11-2.77, p=0.02) (Fig 1-B), and additionally adjusting for Day 0 hs-TnI (HR: 1.72, CI: 1.03-2.85, p=0.04).

Conclusions:
Initial hs-TnI in patients with sepsis and ARDS was not associated with mortality. Increase in hs-TnI of at least 20% by Day 3 was associated with 60-day mortality. Future studies should assess mechanism and treatment of myocardial injury in sepsis.
Abstract 15012: Lactate Dehydrogenase B and Pyruvate Oxidation Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: A Multi-omics Study
Authors: Tantawy Marwa , Chekka Lakshmi Manasa , Garrett Timothy , Singh Sonal , SHAH chintan , Fradley Michael G , Cornell Robert , Baz Rachid , Waheed Nida , DeRemer David , Yuan Lihui , Langaee Taimour Y , March Keith L , Pepine Carl , Moreb Jan , Gong Yan
Published: November 2020

Introduction:
Multiple Myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), a proteasome inhibitor used to treat relapsed and refractory MM, has been associated with cardiotoxicity including heart failure (HF).

Hypothesis:
We hypothesized that a multi-omics approach integrating data from different omics will provide insights into the mechanisms of CFZ-induced HF.

Methods:
Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with symptomatic HF and 6 with no HF) at the University of Florida Health Cancer Center. Global metabolomics profiling was performed using a LC/MS metabolomic platform. Global proteomic profiling was performed on LC/MS/MS platform with ~ 370 proteins quantified by iTRAQ analysis. TaqMan
®
OpenArray
®
Human MicroRNA Panel, containing 754 human microRNAs (miRNAs), was used for miRNA profiling. Pathway integrative analysis was performed to identify genes and pathways that are differentially expressed between those who developed HF versus those who did not. Features with p-value < 0.05 were considered statistically significant.

Results:
The cohort mean age was 61 years and 38.5% were men. Proteomics data identified up-regulation of lactate dehydrogenase B (LDHB) (fold change [FC]=8.2, p=0.01) in those who developed HF compared to those who did not. Metabolomics data identified lower plasma abundance of pyruvate (FC=0.16, p=0.0004) and higher abundance of lactate (FC=2.4, p=0.0001) in HF patients. Using miRNA target gene prediction tools, we observed that LDHB regulated by miR-139 which downregulated in HF patients (FC=0.03). Multi-omics integrative analysis suggested that the pyruvate fermentation to lactate (pyruvate oxidation) pathway is associated with CFZ-related HF.

Conclusion:
In this pilot multi-omics integrative analysis, we observed down-regulation of pyruvate and up-regulation of LDHB among patients with CFZ-related HF, which suggests the importance of pyruvate oxidation pathway and mitochondrial dysfunction in CFZ-related HF and that this pathway might be regulated by miR-139. Further investigation in a larger independent cohort is warranted to better understand the mechanisms of CFZ-related HF.
Abstract 15016: Peak Oxygen Consumption Achieved at the End of Cardiac Rehabilitation Predicts Survival in Patients With Coronary Heart Disease
Authors: Carbone Salvatore , Kim Youngdeok , Kachur Sergey , De Schutter Alban , Billingsley Hayley E , Milani Richard V , LAVIE Carl J
Published: November 2020

Introduction:
Several patients with coronary heart disease (CHD) present reduced survival despite completing cardiac rehabilitation (CR), suggesting that the level of cardiorespiratory fitness (CRF) achieved might remain suboptimal. The purposes of this study were: 1) to examine the independent association of peak oxygen consumption (VO
2
), a measure of CRF, at post-CR with long-term survival; and 2) to establish an optimal cut-off for peak VO
2
at post-CR that best predicts mortality risk.

Methods:
853 patients with CHD (mean age of 64±10 years old) who were referred to CR between January 1, 2000, and June 30, 2013, at Ochsner Medical Center were analyzed for this study. We measured pre- and post-CR peak VO
2
. Mortality data were collected using National Death Index. Cox proportional hazard regression model was used to examine the risk of all-cause mortality associated with peak VO
2
at post-CR, independent of peak VO
2
at pre-CR and related changes during CR. Contal and O’Quigley’s method were used to determine the optimal cut-off for peak VO
2
at post-CR based on a split-sample approach.

Results:
Mean peak VO
2
at post-CR was 21.01±6.25 mL/kg/min (75% and 51% predicted peak VO2 using Wasserman and FRIEND Registry equations, respectively). During a mean follow-up of 6.55 years, 106 subjects (12.4%) died. Peak VO
2
at post-CR independently predicted mortality (Hazard Ratio: 0.82 [0.77-0.87], p<0.001). We identified peak VO
2
of ≥17.6 kg/mL/min as optimal cut-off best predicting survival (
Figure 1, Panel A
) and the %predicted peak VO2 at post-CR ≥62.1% using Wasserman (
Figure 1, Panel B
) and ≥41.4% using FRIEND Registry (
Figure 1, Panel C
) as the alternative optimal cut-offs.

Conclusions:
In patients with CHD undergoing CR, post-CR peak VO
2
independently predicts long-term survival. These results suggest that patients with CHD presenting a peak VO
2
lower than the cut-off identified herein may benefit from additional sessions of CR or higher intensity exercise training.
Abstract 15025: Visceral Adiposity and Muscle Composition in Heart Failure With Preserved Ejection Fraction and Association With Exercise Tolerance
Authors: Ying Wendy , Sharma Kavita , Yanek Lisa R , Vaidya Dhananjay , Schar Michael , Markl Michael , Subramanya Vinita , Soleimanifard Sahar , Ouyang Pamela , Michos Erin D , Shah Sanjiv J , Hays Allison G
Published: November 2020

Introduction:
Visceral adipose tissue (AT) promotes inflammation and adverse metabolic changes that mediate disease progression in heart failure with preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but little is known about its relation to the extent and distribution of AT. We characterized regional AT distribution in HFpEF patients and controls and analyzed associations with comorbidities and exercise tolerance.

Methods:
MRI was performed to quantify epicardial, liver, abdominal and thigh skeletal muscle AT. We assessed NYHA class, 6-minute walk distance (6MWD), and global well-being score (GWBS). Multivariable linear and logistic regression models were used, adjusted for age, sex, and body surface area.

Results:
We studied 55 HFpEF patients (41 women, mean age 67) and 33 controls (21 women, mean age 57). Epicardial AT (4.6 vs 3.2mm, p = 0.03), thigh intermuscular fat (11.0 vs 5.0cm
2
, p < 0.01) and liver fat fraction (FF) (6.4% vs 4.1%, p = 0.04) were higher in HFpEF patients than controls. Women with HFpEF had higher abdominal (443.9 vs 297.3 cm
2
, p = 0.03) and thigh (228.6 vs 112.3 cm
2
, p < 0.001) subcutaneous AT than men. Higher thigh intermuscular fat was associated with higher blood pressure (β [SE] 14.1 [3.3], p < 0.001) and diabetes (β [SE] 2.6 [1.1], p = 0.02), and liver FF was associated with chronic kidney disease (β [SE] 1.6 [0.6], p = 0.01). Higher thigh intramuscular fat was associated with both higher NYHA class and shorter 6MWD, and higher thigh intermuscular AT FF was associated with higher NYHA class (
Table
). Higher epicardial AT and liver FF were associated with lower GWBS.

Conclusions:
HFpEF patients have increased epicardial, liver, and skeletal muscle fat compared to controls out of proportion to their body size, and adiposity was associated with worse exercise intolerance in HFpEF. These results provide the basis for further investigation into regional AT distribution in relation to HFpEF symptoms and pathophysiology.
Abstract 15029: Atrial Arrhythmias and Pulmonary Hypertension Across Wsph Groups
Authors: Rosenzweig Erika B , Radeva Milena , Frantz Robert , Hassoun Paul M , Hemnes Anna R , Horn Evelyn M , Leopold Jane A , Rischard Franz , Tang Wilson ,   the PVDOMICS Study Group
Published: November 2020

Introduction:
Previous reports have shown that atrial and ventricular arrhythmias (VA) are common in all forms of pulmonary hypertension (PH) with prevalence of supraventricular arrhythmias ranging from 13-25% and VA 27%. Arrhythmias are also associated with clinical worsening events. Reports have limited numbers of patients with a variety of forms of PH and limited data comparing the prevalence of atrial arrhythmias across WSPH groups and whether advancing age, WHO FC, echocardiographic, exercise capacity and hemodynamic patterns are associated with a higher prevalence of atrial arrhythmias.

Methods:
As part of the PVDOMICS program, we enrolled 1195 PH participants, controls and PH comparators and prospectively collected electrocardiograms (ECGs) at enrollment for 1147 of them. Comparisons across participants with and without atrial fibrillation/atrial flutter (afib/flutter) used analysis of variance (ANOVA) or Kruskal-Wallis test in continuous variables based on distribution with statistics presented as mean
+
SD or median [P25, P75] respectively. Pearson’s chi-square test was used for categorical variables.

Results:
Of 732 PH participants (467F) who had ECGs available at baseline, 527 (72.0%) were in normal sinus rhythm and 62 had afib/flutter (8.5%). Afib/flutter participants were older (75
+
8 vs 57
+
14 years; p<0.001), most commonly in WSPH group 2 (28.1%) vs. WSPH 1 (3.3%), WSPH 3(6.5%) and WSPH group 4 (3.7%), had predominantly WHO FC II/III symptoms (89.5%), higher RAP (12.6
+
5 vs.7.8
+
5mmHg; p<0.001) and PCWPm (17.8
+
5.8 vs. 12.3
+
6.2mmHg; p<0.001) and lower CO (4.3+ 1.5 vs. 5.2 +1.8L/min;p<0.001). Participants with afib/flutter had lower 6MWD 277
+
117 vs.356
+
134meters (p<0.001) than PH participants without. Echocardiography demonstrated increase in LA volume index (mL/m2), RA volume (mL) and tricuspid regurgitation severity with reduced TAPSE and LVEF (54
+
10 vs. 61
+
10%;p<0.001). ProBNP was higher in afib/flutter participants 2029 [1073, 2964] vs.268 [100, 1074]pg/ml; P<0.001)

Conclusions:
In this analysis of atrial arrhythmias in a large cohort of PH participants across all WSPH groups, afib/flutter was present most often in older WSPH group 2 patients who demonstrated clinical and hemodynamic features of worse heart failure.