bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11784: Machine Learning Analysis of Progression From Moderate to Severe Tricuspid Regurgitation
Authors: Hudson Olivia , Gastanadui Maria Gabriela , Sotelo Miguel , wagner loren , Rogers Chris , Efstathia Andrikopoulou
Published: March 2022

Background:
Tricuspid regurgitation (TR) is linked to poor outcomes and its progression is associated with higher mortality. Left heart disease, age and sex are factors related to TR progression. We assessed echocardiographic (Echo) and demographic predictors of moderate TR progression using Machine Learning Natural Language Processing (ML NLP).

Methods:
54,315 patients were retrospectively assessed for moderate TR with an Echo between May 2017 to October 2020 and a follow-up Echo 30 days to 113 months. Exclusion criteria included prior pacemaker/ICD, tricuspid prosthesis or band/ring, history of Ebstein, tetralogy of Fallot and tricuspid endocarditis. Cardiac Intelligence
TM
(Mpirik, Milwaukee, WI) identified moderate TR, demographic and Echo indices using ML NLP of the Echo report. Our endpoint was progression from moderate to severe TR within 1 or 2 years. Univariate Cox proportional hazard model was used with univariate analysis.

Results:
Of 3,489 moderate TR patients, 1,564 had a subsequent Echo and 771 met study criteria. Table 1 shows baseline demographic and Echo data. 15% and 24% of moderate TR patients progressed to severe TR within 1 and 2 years, respectively. Black race, left ventricular size, moderate/severe right ventricular (RV) dysfunction and Doppler-based RV systolic pressure were found to be univariate predictors of progression (Figure 1).

Conclusion:
ML NLP based on input from Echo-derived parameters using a real-world sample can offer insights into risk stratification of moderate TR regarding risk of progression to severe disease. Including further clinical and demographic variables will allow to improve performance of a disease prediction ML model.
Abstract 11785: National Hospitalizations for Supraventricular Tachycardia in the United States, 2010 Through 2017
Authors: Agarwal Manyoo , Do Duc H , Ziaeian Boback , Bradfield Jason , Fonarow Gregg C , Buch Eric F
Published: March 2022

Background:
Little data exists describing the national burden of supraventricular tachycardia (SVT) related hospitalizations on US healthcare system. The objectives of this study are to examine the temporal trends of SVT-related hospitalizations in the United States and to compare patient characteristics, outcomes, and comorbid diagnoses.

Methods:
Using the Nationwide Readmission Database from 2010 through 2017, we identified adult (age >17 years) SVT-related hospitalizations using

International Classification of Diseases, 9
th
/10th Revision, Clinical Modification

codes- 427.0/I47.1 as the principal discharge diagnosis.

Results:
There were 192,853 adult hospitalizations for SVT from 2010 to 2017 across United States. The number of hospitalizations increased from 22,313 in 2010 to 39,216 in 2017. Mean age was 63.9 years, 56.8% females and 55.8% Medicare insured. The proportion of comorbid diagnoses in overall cohort: hypertension 66.4%, diabetes 26.9%, hyperlipidemia 42.8%, coronary artery disease 31.6%, atrial fibrillation 30.0%, cerebrovascular disease 3.4%, renal disease 18.8%, liver disease 4.2% and chronic pulmonary disease 14.7%. From 2010 to 2017, following trends were observed: mean age (63.7 years to 64.1 years), females (59.5% to 54.4%), Medicare insured (53.8% to 57.0%), hypertension (62.2% to 70.0%), diabetes (25.3% to 27.5%), hyperlipidemia (39.6% to 45.0%), coronary artery disease (28.6% to 34.8%), cerebrovascular disease (3.0% to 3.3%), renal disease (12.9% to 23.0%), liver disease (4.5% to 2.8%) and chronic pulmonary disease (13.0% to 16.4%). The overall unadjusted in-hospital mortality was 0.6% and mean length of stay was 3.0 days. The trends of mortality and length of stay changed as follows: 0.5% in 2010 to 0.6% in 2017 and 2.9 days to 3.1 days respectively. Mean hospital charges (in USD) were 40,943 and increased from 31,755 in 2010 to 47,830 in 2017.

Conclusions:
The number of hospitalizations for SVT have increased among US adults from 2010 to 2017. The proportion of comorbid chronic diseases, in-hospital mortality and the hospitalization charges also increased during the period of analysis.
Abstract 11802: Evaluation of Family Risk of Rheumatic Heart Disease With Systematic Echocardiographic Screening: Data From the Provar+ Study
Authors: Franco Juliane , Nascimento Bruno R , Oliveira Kaciane , Barbosa Marcia , Arantes Nayana F , Beaton Andrea Z , Mello Luana A , Nascif Maria Cecília L , Oliveira Guilherme C , Camargos Mucelli Spolaor Breno C , Campos Carolina F , Silva Victor R , Nogueira Marcelo Augusto A , Ribeiro Antonio L , Sable Craig A , Nunes Maria P
Published: March 2022

Introduction:
Rheumatic Heart Disease (RHD) is determined by a complex interaction between socioeconomic environment and host susceptibility. Relatives of patients with advanced RHD share both, and may be at high-risk. We aimed to use echocardiographic (echo) family screening to evaluate the risk of RHD among 1
st
degree relatives of patients with advanced RHD.

Methods:
From Feb 2020 - Jun 2021 patients with advanced RHD were consecutively enrolled in the University Hospital’s outpatient clinics. Consented 1
st
degree relatives were invited for echo screening (2012 World Heart Federation Criteria) utilizing handheld devices (GE VSCAN) by non-physicians, with telemedicine interpretation by 2 experts. Matched controls (spouses, neighbors) living in the same household were also enrolled in a 1:5 fashion. A confirmatory full echo (GE Vivid IQ) was scheduled if abnormalities were observed, and all positive RHD cases were referred for follow-up.

Results:
In 16 months, 202 relatives and 42 controls of 117 patients were screened, including 114 children, 68 siblings and 20 parents. Mean age was 41±18 years, 62% were women and 214 (88%) lived with the index case for >10 years. At total 51 (21%) individuals had hypertension, 17 (7%) diabetes, 5 reported a previous stroke and only 5 (all relatives) had personal history of RHD. Among index cases, 73% reported current or past prescription of Penicillin. Echo findings suggestive of RHD were observed in 0 controls and 14 (7%) relatives (p=0.08), being 11 with mitral valve (MV) disease and 3 with mixed (mitral and aortic valve (AV)) disease. Eleven patients had mild/moderate MV regurgitation, 4 with associated MV stenosis and abnormal morphology. Two patients had mild AV regurgitation and abnormal AV morphology, associated with mild AV and MV stenosis, and 1 patient had bioprostheses in the MV and AV. One case of mild left ventricular dysfunction was observed, and 1 patient had indication of commissurotomy for MV stenosis at the time of diagnosis.

Conclusions:
First-degree relatives of individuals with clinical RHD are at greater risk of having RHD and family screening should be considered. Genotyping studies are warranted to better understand individual and family susceptibility to RHD, in addition to socioeconomic conditions.
Abstract 11805: Identifying Novel Genetic Variants Associated With an Increased Risk of Cerebrovascular Disease Using a Large-Scale Bio-Medical Database
Authors: Alkhalfan Fahad , Gyftopoulos Alex , Chen Yi-Ju , Williams Charles H , Perry James A , Hong Charles C
Published: March 2022

Introduction:
Cerebrovascular disease occurs because of a complex interplay between vascular, environmental, and genetic factors. It is the second leading cause of disability worldwide. Understanding who may be genetically predisposed to cerebrovascular disease can help guide preventative efforts. We aim to utilize the UK Biobank to identify genetic variants associated with an increased risk of cerebrovascular disease.

Methods:
The UK Biobank is a prospective cohort containing clinical and genetic data gathered from over 500,000 individuals. We used Plink’s GLM options to analyze associations between genotypes and phenotypic manifestations of the disease. We defined cerebrovascular disease by selecting the ICD-10 codes G45, G46, I63-I67 and I69. We compared cases to age- and gender-matched controls with a case-to-control ratio of 20:1. Related individuals and those with confounding diagnoses such as coronary artery disease and other atherosclerotic conditions were excluded from the controls.

Results:
There were 9,726 and 6,699 instances of cerebrovascular disease as a primary or secondary diagnosis. We identified 189 variants in 8 different genes with
p
≤ 1x 10
-6
. Identified genes have a minor allele frequency ≥ 0.5%. Variants with the highest significance were identified in close proximity to sequences encoding
PITX2
(Paired like homeodomain 2;
p
= 2.4 x 10
-9
, OR = 1.1),
LPA
(Lipoprotein(a);
p
= 6.1 x 10
-9
, OR = 7.3),
LRRTM4
(leucine rich repeat transmembrane neuronal 4;
p
= 1.8 x 10
-8
, OR = 1.08), and
CDKN2B-AS1
(CDKN2B antisense RNA 1;
p
= 4.5 x 10
-8
, OR = 0.93).

Conclusions:
Through genome-wide analysis using ICD-10 codes as a phenotype for cerebrovascular diseases, we identified several novel genetic variants that are significantly associated with the incidence of cerebrovascular disease in the UK Biobank. Some of the associated genes were previously shown to be associated with atrial fibrillation (
PITX2
), and atherosclerosis (
LPA
and
CDKN2B-AS1
), solidifying the contribution of these two clinical risk factors to cerebrovascular accidents.
LRRTM4
was previously associated with cognitive impairment, supporting a biologically plausible link to cerebrovascular disease. Future studies are warranted to confirm the findings of this analysis.
Abstract 11806: CT Measure of Intraparenchymal Vascular Volume in Chronic Obstructive Pulmonary Disease Patients With and Without Pulmonary Hypertension
Authors: Lakshman Sneha , Ahmad Imama , Nardelli Pietro , San Jose Estepar Ruben , San Jose Estepar Raul , Washko George , Rahaghi Farbod
Published: March 2022

Purpose:
Pulmonary hypertension, despite oxygen therapy, remains a major comorbidity of COPD. Pruning in the form of loss of small vessel fractional volume has been shown to be associated with right heart disease and poor outcomes in COPD. In this investigation we sought to investigate the relationship between this marker and the presence of precapillary pulmonary hypertension by hemodynamic measures.

Methods:
We conducted an automated search of patients at Brigham and Women’s Hospital with the diagnosis and PFTs consistent with COPD, CT pulmonary angiography and RHC timed within a year. Patients with other forms of lung disease, risk factors for group 1 PH, poor image quality, active lung infection or lung collapse were excluded. All data collection was approved by the IRB at Mass General Brigham (IRB #2018P000419).Using the Chest Imaging Platform (
www.chestimagingplatform.org
) we measured the total vascular volume (TBV), the small (vessels with a cross sectional area <= 5 mm
2
, BV5) and large ( > 5mm
2
, BVg5) for both the arteries and the veins; The small vessel fraction (BV5/TBV) a marker of pruning, and ratio of arterial to venous volumes were also calculated and analyzed using Wilcoxon Rank-sum and modeled using linear regression in R version 4.0.1

Results:
Of the Total Cohort (N=44), 17 had precapillary PH (prePH), 12 had PH associated with elevated wedge pressures (pcPH) and the remaining 15 did not meet diagnostic criteria for PH. Patients with prePH had a lower arterial but not venous BV5/TBV (prePH: 0.39 vs noPH: 0.46, p = 0.04) and higher arterial to venous volume ratios for large vessels (1.95 vs 1.38 p = 0.008) compared to patients without PH. In a linear regression models, lower arterial but not venous small vessel fraction continued to be related to mean pulmonary artery pressures after adjustment for age and gender (p = 0.01).

Conclusions:
In this retrospective study of COPD patients with CT angiography and hemodynamic assessment, decreased small arterial vascular fraction derived from 3D reconstruction of the intraparenchymal vasculature was associated with increased mPAP and was higher in patients with precapillary PH compared to controls.
Abstract 11811: Impact of Anemia on the Outcomes of Hospitalizations for Atrial Fibrillation: Analysis of National Inpatient Sample
Authors: Almani Muhammad , Usman Muhammad , Richard Trohman , Santos Volgman Annabelle , Ayub Muhammad
Published: March 2022

Introduction:
Anemia is a known adverse prognostic factor among patients with cardiovascular diseases. We sought to determine the impact of anemia on hospitalizations for atrial fibrillation (AF).

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2016 - 2018 Database. The NIS was searched for hospitalizations for adult patients with AF as principal discharge diagnosis with and without anemia as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Multivariate logistic and linear regression analysis were used accordingly to adjust for confounders. STATA software was used for analysis.

Results:
Of the 1,236,549 patients admitted for AF, 196,430 (15.9%) had anemia. The mean age of patients with anemia was 74 years (95% CI 73.8 - 74.1) vs. 70 years (95% CI 70.2 - 70.3) at the time of admission for AF (p<0.001). There were 56.6% females in the Anemia group vs. 50.3% in the other group (p<0.001). The adjusted odds ratio (aOR) for inpatient mortality for AF with anemia compared to AF without anemia was 1.53 (95% CI 1.388 - 1.686, p<0.001). Patients with anemia averaged 1.23 days longer length of stay (95% CI 1.182 - 1.287, p<0.001) and 14112 USD higher mean hospitalization charge (95% CI 13179 - 15046, p<0.001). Comorbid anemia in AF patients was associated with higher risks of cardiac arrest (aOR 1.61; 95% CI 1.38 - 1.87, p<0.001) and cardiogenic shock (aOR 1.84; 95% CI 1.61 - 2.10, p<0.001) and a lower likelihood of cardioversion (aOR 0.73; 95% CI 0.71 - 0.76, p<0.001). Detailed outcomes are listed in Table 1.

Conclusions:
Comorbid anemia leads to worse outcomes in patients with AF. Early detection and treatment of anemia in at-risk patients may improve clinical outcomes in AF.
Abstract 11815: Statin Intolerance is Predicted by Intolerance to Multiple Others Drugs: Results of a Large Real-World Experience
Authors: Anderson Jeffrey L , Le Viet T , Bair Tami L , Knight Stacey , Ronnow Brianna , Muhlestein Joseph B , Knowlton Kirk U , Horne Benjamin D
Published: March 2022

Background:
Dealing with statin intolerance represents a major clinical challenge. Controlled clinical trials suggest that a large percentage of statin intolerance may be due to a “nocebo effect”, wherein adverse reactions are linked to pill ingestion irrespective of actual pill content (e.g., SAMSON trial). We tested whether statin intolerance was associated with intolerance to other medications in a large real-world experience. We hypothesized that statin intolerance would be associated with multiple drug intolerances.

Methods:
We searched Intermountain Healthcare medical records between January 2002 and February 2021 for patients (pts) with a listed intolerance or allergy to 1 or more statins. We compared these to a control group of randomly selected pts not exposed to statins but taking one or more other oral medications. A second control group included all patients taking and tolerating statin therapy. We compared the number of recorded drug allergies/intolerances in the statin intolerant group with those in the 2 control groups.

Results:
Characteristics of patients in the 3 groups are shown in the Table. On average, statin intolerant patients had 3.64 additional listed drug allergies/intolerances (beyond statins), compared to 1.31 in non-statin exposed controls and 1.81 in the statin tolerant population (both p<.001).

Conclusion:
In this large real-world experience, statin intolerance was strongly associated with intolerance to multiple other medications. Although some patients may have a true intolerance to multiple medications, including statins, patients with multiple drug intolerances may also suffer from a generalized nocebo effect. In either case, noting a patient’s tendency toward multiple drug intolerances can alert clinicians to an increased intolerance risk when initiating a statin and can lead to preemptive medical and educational interventions aimed at reducing this risk.
Abstract 11820: Physician-Adjudicated Heart Failure Phenotypes Among Patients With Chronic Inflammatory Diseases
Authors: Underberg Daniel , Rivera Adovich , Sinha Arjun , Feinstein Matthew J
Published: March 2022

Objective:
To characterize clinical phenotypes of incident heart failure (HF) among patients with various chronic inflammatory diseases (CIDs).

Background:
Several CIDs are associated with increased HF risk, but differences in HF phenotypes across CIDs are incompletely understood. No prior studies to our knowledge have adjudicated HF phenotypes with physician chart review across a spectrum of CIDs.

Methods:
We screened for patients with CIDs (and controls without CIDs) who had possible HF in a large urban medical system, then performed physician adjudication of HF endpoints. Possible HF was based on the intentionally sensitive criterion of a single inpatient or outpatient administrative code for HF; we then determined if HF was definite/probable vs. not present using standardized, validated criteria. Charts of patients with adjudicated HF were queried to define specific HF phenotypes. We then compared clinical, demographic, and HF phenotypic characteristics for HF patients with specific CIDs vs. non-CID controls using Fisher’s exact test.

Results:
Out of 415 patients with at least one code for HF, 192 had definite/probable HF. We observed significant differences in HF phenotypes across CIDs (Table 1). Isolated right-sided HF was more than twice as common in patients with scleroderma (27.8%) than in any other CID. Left ventricular systolic dysfunction was most common in patients with HIV and lupus (SLE); mean LVEF was 45.0% ± 18.6% for HIV and 41.3% ± 17.1% for SLE, while it was 57.7% ± 10.7% for scleroderma. Those with HIV and multiple CIDs were most likely to have coronary artery disease.

Conclusions:
Different CIDs are associated with different phenotypic presentations of physician-adjudicated HF, which may reflect different underlying inflammatory pathophysiologies. Future studies in larger, multi-center cohorts are needed to confirm these findings, as are mechanistic studies focused on understanding specific immunoregulatory contributors to HF.
Abstract 11821: Telomerase Therapy Reverses Vascular Senescence and Extends Lifespan in Progeria Mice
Authors: Mojiri Anahita , Walther Brandon , Jiang Chongming , Matrone Gianfranco , Holgate Rhonda , Xu Qiu , Morales Elisa , Wang Guangyu , gu jianhua , Wang Rongfu , Cooke John P
Published: March 2022

Background:
Hutchinson-Gilford Progeria Syndrome (HGPS) is an accelerated aging syndrome associated with premature vascular disease and death due to heart attack and stroke. In HGPS a mutation in lamin A (progerin), alters nuclear morphology and gene expression. Current therapy increases the lifespan of these children only modestly. Thus, greater understanding of the underlying mechanisms of HGPS is required to improve therapy. Endothelial cells (ECs) differentiated from induced pluripotent stem cells (iPSCs) derived from these patients exhibit hallmarks of senescence including replication arrest, DNA damage, increased expression of inflammatory markers and telomere erosion. We hypothesized that correction of shortened telomeres may reverse these measures of vascular aging.

Methods:
We generated ECs from iPSCs belong to children with HGPS and their unaffected parents. Telomerase mRNA (hTERT) was used to treat HGPS ECs. Endothelial morphology and functions were assessed, as well as proteomic and transcriptional profiles with attention to inflammatory markers, DNA damage and EC identity genes. In a mouse model of HGPS, we assessed the effects of lentiviral transfection of mTERT on measures of senescence, focusing on the EC phenotype in various organs.

Results:
hTERT treatment of human HGPS ECs improved replicative capacity; restored endothelial functions such as nitric oxide generation, acLDL uptake and angiogenesis; and reduced the elaboration of inflammatory cytokines. In addition, hTERT treatment improved cellular and nuclear morphology, in association with a normalization of the transcriptional profile, effects which may be mediated in part by a reduction in progerin expression and an increase in SIRT1. Progeria mice treated with mTERT Lentivirus manifested similar improvements, with a reduction in inflammatory and DNA damage markers and increased SIRT1 in their vasculature and other organs. Furthermore, mTERT therapy increased the lifespan of HGPS mice.

Conclusion:
Vascular rejuvenation using telomerase mRNA is a promising approach for progeria and other age-related diseases.
Abstract 11822: Comparison of Outcome of Cardiopulmonary Resuscitation in COVID Positive versus COVID Negative Patients; a Tertiary Care Hospital Experience From Pakistan Cardiopulmonary Resuscitation in COVID Positive versus COVID Negative Patients
Authors: Ahmed Amber , iqbal madiha , Khan MFAISAL , Hirani Sana
Published: March 2022

Introduction:
The impact of Covid-19 on outcomes of In-hospital cardiac arrest IHCA remains unclear.

Aims & Methodology:
We, conducted a retrospective cohort study to compare the characteristics and outcome of CPR in Covid positive V/s Covid negative patients, at our institute. Data were retrieved from a review of the medical records of all patients who underwent cardiac arrest during the pandemic period. Taking Covid-19 as the exposure variable, our sample population was divided into two cohorts.

Results:
Eighty patients who underwent CPR were included in the study with;40 patients in each group. The mean age was 61 in the positive group and 65 in the negative group. The male to female ratio was equal in the covid positive group but the male population was higher in the negative group. (77%). The most frequent comorbidities were the same (Diabetes, hypertension, and ischaemic heart disease) in both groups. All of the patients had ARDS in Covid positive group while septic shock was the commonest diagnosis (48.9%) in the negative group. In the positive group, 74% of patients were in high dependency unit (HDU) and 26% were in ICU. In the negative group,94% of patients were in HDU and 6% in ICU. The initial rhythm was Pulseless electrical activity (PEA) in 52% of the positive group and all of the patients (100%) in the negative group. Eight percent of covid positive patients had shockable rhythm while remaining had asystole. The median duration of CPR was 15 minutes in the positive group and 17 minutes in the negative group. Although the return of spontaneous circulation (ROSC) was achieved in 14% of patients in covid positive, none of them survived to discharge. In the negative group, 30% of patients achieved ROSC while survival to discharge was 15%. The odds of mortality were 6.88 [95% confidence interval (CI)0.789-60] times higher in COVID-19-positive patients, compared to negative patients.

Conclusions:
Covid-19 infection is associated with poor outcomes in IHCA compared to non-covid illnesses.
Abstract 11823: Machine Learning-Based Model for Prediction of All-Cause Mortality in Low Ejection Function Patients
Authors: Sakashita Yuji , Kawamura Ai , Kashiyama Noriyuki , Kawamura Takuji , Yoshioka Daisuke , Toda Koichi , Miyagawa Shigeru
Published: March 2022

Introduction:
It is important to accurately predict heart failure prognosis for quality of life and selection of the treatment. In this article, we developed the prediction model based on machine learning and show how each variable used in the prediction model contributed to the prediction.

Methods:
We developed the 5-year all-cause mortality prediction model by machine learning. The database contained 1227 cases and 232 variables. We dropped the variables which had over 20% of missing value. We split the database into 80% as training data and 20% as test data. We selected the variables for model development by statistical methods, algorithm-based method, and past findings. The models were developed using selected variables and evaluated the performance with the area under the curve. The best-performing model was analyzed how each variable contributed to the prediction by the SHapley Additive exPlanations (SHAP).

Results:
We selected 19 variables by statistical methods, algorithm-based method, and past findings for the model development. The best model has used six variables, age, creatinine, body surface area, blood urea nitrogen, diabetes mellitus, and emergency hospitalization from all combinations of variables. The AUC was 0.80 in training data and 0.79 in test data. We showed the contributions of variables to the prediction by SHAP in Figure. The variables listed in higher were more affected to the prediction value. The values positioned in more right were contributed to survival.

Conclusions:
We successfully developed the prediction model using six variables and with good AUC.
Abstract 11825: The Association Between Frailty and Vascular Endothelial Growth Factor Families in Patients With Heart Failure: The PREHOSP-CHF Study
Authors: Iguchi Moritake , Wada Hiromichi , Shinozaki Tsuyoshi , suzuki masahiro , Ajiro Yoichi , Matsuda Morihiro , Koike Akihiro , Koizumi Tomomi , shimizu masatoshi , Ono Yujiro , Takenaka Takashi , Sakagami Satoru , Morita Yukiko , Fujimoto Kazuteru , Yonezawa Kazuya , Yoshida Kazuro , Ninomiya Akiyo , Nakamura Toshihiro , FUNADA JUNICHI , Kajikawa Yutaka , Oishi Yoshifumi , Kato Toru , Kotani Kazuhiko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji
Published: March 2022

Background:
Frailty is a complex clinical syndrome associated with ageing and chronic illness, and is common in heart failure (HF). Vascular endothelial dysfunction including maladaptive angiogenesis and lymphangiogenesis is involved in the pathogenesis of HF, and is also considered to be the causes of frailty. We investigated the association of vascular endothelial growth factor (VEGF) families, central regulators of angiogenesis and lymphangiogenesis, with frailty, and prognostic role of these cytokines in frail HF patients.

Methods:
We performed a multicenter prospective cohort study to determine the predictive value of VEGF families for prognosis among patients with HF. A total of 1,024 patients (mean age, 75.5 years, 58.7% male) were included in the analyses. Serum levels of VEGF, VEGF-C, VEGF-D, and soluble VEGF receptor-2 (sVEGFR-2) were measured. Frailty was assessed by Canadian Study of Health and Aging Clinical Frailty Scale (CFS).

Results:
A total of 256 (25.1%) patients had frailty (CFS≥5) at baseline. Frail patients were older, more likely female, and had lower body mass index, higher NYHA class, and higher rates of prior hospitalization for HF, HF with preserved ejection fraction, anemia, cerebrovascular disease, and dementia. N-terminal pro brain natriuretic peptide, high sensitivity troponin I, and high sensitivity C-reactive protein levels were higher in frail patients. During the 2-year follow-up, 211 all cause death occurred. In Kaplan-Maier analysis, frail patients showed significantly higher incidence of all-cause (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.14-5.42). Regarding VEGF families, frail patients had significantly lower levels of sVEGFR-2 and VEGF-C, and higher levels of VEGF-D. Multiple regression analysis revealed that VEGF-C had inverse correlation with CFS (P, 0.03). After adjusting for clinical confounders, a low VEGF-C level was independently associated with all-cause death in frail patients (HR, 0.74; 95%CI, 0.58-0.94 for 1-SD increase), but was not in non-frail patients (HR, 0.87; 95%CI, 0.64-1.14 for 1-SD increase) (P for interaction, 0.09).

Conclusions:
In HF patients, a low VEGF-C value was associated with frailty and was independent risk for all-cause death in frail patients.
Abstract 11836: Higher Burden of Supraventricular Ectopy is Independently Associated With Greater Risk of Dementia in Older Adults Without Atrial Fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Parikh Romil R , Wang Wendy , Rooney Mary R , Zhang Michael J , Vant Hof Jeremy R , Matsushita Kuni , Soliman Elsayed Z , Windham B Gwen , Mosley Thomas , Pike James R , Wasserman Bruce A , Johansen Michelle C , Gottesman Rebecca F , Alonso Alvaro , Chen Lin Y
Published: March 2022

Introduction:
In older adults without atrial fibrillation (AF), it is unclear if higher burden of supraventricular ectopy (SVE) is associated with dementia risk independent of cardiovascular risk factors and clinically documented stroke.

Hypothesis:
In older adults without AF, higher burden of SVE including premature atrial contractions (PAC) and atrial tachycardias (AT) are associated with a higher risk of dementia.

Methods:
Among 2167 participants (mean age, 79 years, 60% female, 26% Black) without adjudicated dementia, stroke or AF, at baseline (2016-17), AT and PAC were measured over 2 weeks by an ambulatory, continuous electrocardiogram recorder (Zio XT patch, iRhythm Technologies, Inc.). We quantified burden of PACs and ATs as: 1) natural log of frequency (episodes/day) due to skewed distributions, and 2) a dichotomous frequency measure, split at the median. Additionally, we dichotomized duration of the longest AT episode at the median. Dementia was adjudicated based on cognitive assessments through 2019 using the Clinical Dementia Rating scale at study visits or by telephone cognitive interviews, informant interviews, and ongoing linkage to medical records. We calculated relative risk of incident dementia using Poisson regression with robust error variance.

Results:
At baseline, median Zio XT patch wear time was 13.8 days (interquartile interval 13-14 days). Over 2 years of follow-up, 66 (3.0%) participants developed dementia. Higher frequency of AT and PAC (continuous or dichotomous) were associated with a higher risk of dementia independent of incident AF, stroke, and cardiovascular risk factors (Table).

Conclusions:
In older adults without AF, higher burden of SVE is associated with a greater risk of dementia independent of incident AF, stroke, and cardiovascular risk factors. Future research should define underlying mechanisms and evaluate the effect of lowering SVE burden on the risk of dementia in older adults with a higher SVE burden.
Abstract 11839: Outcomes of Stroke and Bleeding by Class of Anticoagulant Use for Non-Valvular Atrial Fibrillation in Patients With Active Cancer
Authors: Patel Ashley , Khawaja Muzamil , Chen Christopher R , Zheng Henry , Morgan Jacob , Kaczmarek Jessica , Gao Feng , Karimzad Kaveh , Song Juhee , Lopez-Mattei Juan , Iliescu Cezar , Deswal Anita M , Palaskas Nicolas L
Published: March 2022

Introduction:
The choice of anticoagulant for patients with non-valvular atrial fibrillation (AF) in the setting of active cancer has not been well studied given only a minority of patients with cancer included in clinical trials.

Hypothesis:
Cancer patients will have similar rates of stroke (CVA), gastrointestinal bleeding (GIB), and intracranial hemorrhage (ICH) when treated with direct oral anticoagulants (DOAC) compared to warfarin (VKA) for AF.

Methods:
A retrospective study was performed at MD Anderson Cancer Center on patients with cancer and AF being treated with VKA or DOAC. The outcomes assessed were overall mortality, CVA, GIB, or ICH and patients were censored at 5 years. 1:1 propensity score matching was conducted to select comparable patients receiving VKA versus DOAC. Multivariable Cox proportional hazards regression models were fitted for each outcome.

Results:
A total of 1133 patients were included in the dataset with mean age of 72 years, 42% women, and 74% received DOAC (57% received apixaban). At 5 year follow up, mortality occurred in 145, CVA in 59, GIB in 59, and ICH in 6 patients. The baseline risk scores were higher for those on VKA compared to DOAC (CHADSVASC 3.5±1.6 vs 3.3±1.7 p=0.04, HASBLED 2.0 ± 1.1 vs 1.8 ± 1.0 p<0.01). After propensity score matching 210 patients were included in each anticoagulant group. Survival analysis showed higher GIB free survival in the DOAC group however no difference was observed for composite GIB, CVA, or ICH (Figure). On multivariate analysis the risk of GIB was higher in the VKA group (HR 3.1, 95% CI 1.3-7.3); however, risk of mortality (HR 1.1, 95% CI 0.7-1.8), CVA (HR 0.9, 95% CI 0.4-1.8), ICH (HR 0.3, 95% CI 0.0-2.2), and composite of GIB, CVA, or ICH (HR 1.3, 95% CI 0.8-2.3) were not different comparing VKA to the DOAC propensity matched group.

Conclusion:
Patients with active cancer have higher risk of GIB but similar overall survival and risk for composite stroke and bleeding when treated with VKA compared to DOAC for AF.
Abstract 11842: Graft Flushing Solution Applies Myocardial Protection Properties in Coronary Artery Bypass Grafting
Authors: Szalkiewicz Philipp , Emmert Maximilian Y , Heinisch Paul , Arnold Zsuzsanna , Ingo Crailsheim , Markus Mach , Grabenwöger Martin , Winkler Bernhard
Published: March 2022

Introduction:
In on-pump coronary artery bypass grafting (CABG) procedures testing of the distal anastomoses via repeated flushing of graft storage solution perfuses at a certain extent the downstream myocardium. This study evaluated the impact of specific solutions on myocardial protection during CABG procedures.

Hypothesis:
Duragraft® (Somaluthion, Jupiter FL,USA) storage solution exhibits beneficial myocardial protection compared to 0.9% Saline/Biseko® (Biotest Pharma GmbH, Dreieich, Germany).

Methods:
Between 7/2019 - 3/2020 either Duragraft® (Group A) or 0.9% Saline/Biseko (Group B) was applied during 272 CABG procedures. After propensity matching 166 patients of identical group size (male: 86.7%; 68.1 ± 9.3 years) were analyzed in this single center retrospective study. Cardiac enzymes were evaluated after CABG during hospital stay and compared between both groups.

Results:
The mean count of venous and overall grafts was 1.5 (± 0.5) and 2.6 (±0.7). No clear difference in the distribution pattern of Creatine Kinase was observed, while high sensitive Troponin I (in nanogram per liter) were significantly lower in Group A at 12-24 hours (4384.9 (± 5509.6) vs. 11566.9 (± 31505,1); p= 0.042), two days (1931.9 (± 3079.8) vs. 4978.5 (± 9145.6); p= 0.05), three days (1473.3 (± 3207.4) vs. 2939.8 (±5564.5); p= 0.046) four days (992.4 (± 1957.3) vs. 1995 (± 3404.8); p= 0.037) and at the sixth day (716.3 (± 1056,2) vs. 1573.9 (±3013.1); p= 0.046) after surgery.

Conclusions:
Downstream myocardium perfusion with graft solution could provide enhanced myocardial protection in on-pump procedures, with Duragraft® being superior to Saline/Biseko® in terms of Troponin release.
Abstract 11844: Viral Gene Signatures in Patients With Cardiomyopathy After Chemotherapy
Authors: Varkoly Kyle , Tan Shaoyuan , Beladi Roxana , Kraberger Simona , Fath Ayman , Yaron Jordan , Zhang Liqiang , Pepine Carl J , Varsani Arvind , Shah Chintan , Moreb Jan , Schultz-Cherry Stacey , Lucas Alexandra R
Published: March 2022

Introduction:
Chemotherapy for hematologic malignancies can cause severe cardiomyopathy. Chemotherapeutic agents also induce immune suppression increasing the risk of opportunistic infections.

Hypothesis:
We have hypothesized that immunosuppression after chemotherapy increases opportunistic viral infections, myocarditis and cardiomyopathy.

Methods:
Viral gene sequences were identified using an unbiased high-throughput sequencing approach of patient blood samples following chemotherapy treatment for hematological malignancies (N = 28). Detected viral sequences were correlated with cardiac ejection fraction (LVEF) measured before and after treatment.

Results:
In a blinded analysis undertaken by two investigators viral sequences were identified in blood samples from patients after chemotherapy. Low levels of Influenza A, orthomyxovirus and Avian Paramyxovirus sequences were detected but identified individual virus sequences did not have a significant correlation to reduced LVEF post chemotherapy (r = 0.177-0.293). Detected sequences for all RNA viruses combined did indicate some correlation with LVEF, r = 0.621, suggesting potential for nonspecific RNA virus detection ( p < 0.0078). In a secondary broad screen, data mining was performed including all detectable viral sequences without the filtering of human related sequences. In this broad analysis a significant correlation was detected for Paramyxovirus with reduced cardiac LVEF (r = 0.592 post, compared to r = 0.464 prior to chemotherapy; P < .0096). For detected Orthomyxovirus sequences correlations were similar for LVEF pre- and post- chemotherapy (R = 0.483, P < 0.0451). Retroviruses reads were increased but suspect due to human genome retrovirus sequences (R= 0.512; P < 0.0351). No correlation was seen for Anellovirus, a DNA virus. Reduced LVEF did not correlate with chemotherapy (p = NS).

Conclusions:
This is the first report of screening for RNA viruses in the circulating blood of patients post chemotherapy using a high-throughput sequencing approach. Influenza Orthomyxovirus and Avian Paramyxovirus sequences were detectable in patients with reduced LVEF after chemotherapy. Further analysis for RNA virus infections in cardiomyopathy after chemotherapy is warranted.
Abstract 11846: Excess Healthcare Costs and Bed Days Associated With Complications Following Catheter Ablation of Atrial Fibrillation
Authors: Ngo Linh T , Ganesan Anand N , Kaambwa Billingsley , Woodman Richard , Hay Karen , Ranasinghe Isuru
Published: March 2022

Background:
Complications following catheter ablation of atrial fibrillation (AF) have been extensively examined but little is known about their associated economic burden.

Hypothesis:
Complications of AF ablations were associated with a significant increase in healthcare resources utilization.

Methods:
All patients >18 years undergoing AF ablations in the financial years of 2011-2017 in Australia with available cost data from the National Hospital Cost Data Collection were included. The primary outcome was occurrence of any complications up to 30-days post-discharge. All costs were adjusted to 2021 Australian dollars. The increase in length of stay (LOS) and in cost associated with complications, adjusting for patient characteristics, was evaluated using generalized linear models and negative binomial regression.

Results:
Our study included 19,916 patients (mean age 62.6±11.3 years, 30.2% females). The median length of stay was 1 day (interquartile range [IQR] 1-2 days) and the median cost per hospitalization was $6,646.5 (IQR $5,979.7-$10,210.5). A total of 1,074 patients (5.39%) experienced a complication (4.24% during the hospital stay and 1.37% post-discharge). The most common complications were bleeding (3.18%), pericardial effusion (0.66%), and vascular injury (0.43%). On average, the occurrence of a complication was associated with 2.8 excess bed-days and a $6,119.4 (95%CI $5,491.2-$6,747.7) increase in hospitalization cost (totaling nearly $6.6 millions). Complications that required cardiac surgery were associated with the highest incremental cost per patient ($19,958.5 [95%CI $17,304.5-$22,612.6]) but most of excess cost was attributable to bleeding ($4,808.5 per patient, $3,048,596.1 in total, 44.4% of total excess cost) and pericardial effusion ($6,064.8 per patient, $1,073,094.9 in total, 16.3% of total excess cost).

Conclusions:
The occurrence of any complication following AF ablation is associated with a significant economic burden, most of which was attributable to bleeding and pericardial effusion. Strategies to improve procedural safety and reduce healthcare cost should focus on these complications.
Abstract 11853: Serum Matrix Metalloproteinase 2 is Associated With Lower Ventricular Stiffness and Suboptimal Outcomes in Children With Single Right Ventricle Physiology Who Are Under Consideration for Stage 3 Palliation
Authors: Chowdhury Shahryar M , Bandisode Varsha , Rhodes John , Graham Eric M , Atz Andrew M , Menick Donald R
Published: March 2022

Background:
Increased extracellular matrix (ECM) metabolism is associated with poor outcomes in numerous cardiovascular diseases. However, its relationship to outcomes in patients with single right ventricle physiology (SRV) is unknown. The objective of this study was to investigate the association of measures of ECM metabolism to outcomes in SRV patients under consideration for stage 3 palliation (S3P).

Methods:
SRV patients undergoing routine pre-S3P catheterization were prospectively enrolled. Serum matrix metalloproteinase 2 (MMP-2), cardiac magnetic resonance T1 mapping derived extracellular volume (ECV), and pressure-volume loop derived ventricular stiffness (β) by micro-conductance catheter were collected. Controls were age-matched children undergoing closure of clinically insignificant patent ductus arteriosus. SRV were divided into those who had an optimal outcome or suboptimal outcome (hemodynamic concern causing delay in S3P, length of stay ≥ 14 days, heart transplant or death in first year after S3P).

Results:
Of 30 patients, 15 had SRV and 15 were controls; 7 SRV patients had suboptimal outcome. Mean age was 4.2 ± 0.7 years. SRV patients with suboptimal outcome had lower β (p = 0.05) and ECV (p = 0.04) than patients with optimal outcome (Figure A and B, respectively). MMP-2 was lower in SRV patients with suboptimal outcome compared to SRV patients with optimal outcome and controls (Figure C) (p = 0.05). In SRV patients, MMP-2 correlated with β (r = 0.56, p = 0.03).

Conclusion:
In biventricular heart disease characterized by chronically increased afterload, MMP-2, ECV, and ventricular stiffness are elevated. In contrast, this study shows that SRV patients with lower MMP-2, ECV, and ventricular stiffness have worse outcomes at the time of S3P; this suggests immature ECM metabolism leads to poor outcomes in SRV patients. Future studies exploring the mechanism by which immature ECM and dysregulated ECM metabolism influence SRV outcomes are warranted.
Abstract 11855: Disruption of β-arrestin-2 Signaling Resulted in Impaired Systolic and Diastolic Function During Aging
Authors: Rosas Paola C , Capote Andrielle E , Warren Chad M , Chowdhury Shamim , Wolska Beata M , Solaro R J
Published: March 2022

Introduction:
Angiotensin II (ang II) signaling at ang II receptor type 1 (AT1R), which is a G-protein coupled receptor (GPCR), promotes both G-protein signaling as well as β-arrestin-2 signaling. β-arrestin-2 participates in GPCR desensitization, internalization, but also acts a scaffold for adaptive signal transduction that may occur independently or in parallel to G-protein signaling.

Hypothesis:
We tested the hypothesis that β-arrestin-2 is an important element in the preservation of cardiac function during aging.

Methods:
We tested this hypothesis by aging β-arrestin-2 knock-out (KO) mice, and wild-type equivalent (WT) to 12-16 months. We performed echocardiography studies, and Western blot analysis.

Results:
By echocardiography we found that compared to controls aged KO mice exhibited enlarged left atria (2.2±0.1 vs 2.5±0.1 mm) and left ventricular diameters (4.2±0.2 vs 4.5 ±0.1mm) as well as depressed contractility parameters such as s’ (23.2±1.4 vs 21.4±0.8 mm/s) and decreased circumferential fiber shortening velocity (5.5±0.4 vs 4.5±0.2) with preserved ejection fraction (EF>50%). Aged KO also exhibited depressed relaxation parameters such as e’ (29.2±1.4 vs 21.4±0,6 mm/s) and E/e’ (27.4±1.6 vs 35.6±2.0) when compared to WT controls at the same age. Cardiac dysfunction in aged KO mice was correlated with decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302. Among other kinases, cMyBP-C phosphorylation at Ser302 is a PKCε target which activation is negatively regulated by β-arrestin-2 signaling. To determine the direct effects of PKCε over-activation on cMyBP-C phosphorylation, we used mice that over-expresses constitutively active PKC
ε
in the heart. We found that similarly to our aged KO mice, PKCε overexpression model exhibited significantly higher levels of cMyBP-C phosphorylation at Ser302, when aged to 12 - 15 months.

Conclusions:
Deletion of β-arrestin-2 signaling in KO mice affected aged mice, resulting in changes in the phosphorylation of myofilament proteins consisting of decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302 through the unrestricted activity of PKCε. These changes negatively affected systolic and diastolic function in aged KO mice.
Abstract 11858: A Metabolomic Study of Thrombosis After Cardiac Surgery in Children With Congenital Heart Disease
Authors: Adelekan Zainab , Jorgenson Alissa , Watson David , Tang Weihong , FROST JENNIFER , Zupancich Leah , Garland Kathleen , Dassenko David , Edens R Erik , Overman David M , Huntley Marnie T , Li Shengxu
Published: March 2022

Background:
Thrombosis is a major complication after cardiac surgery in children with congenital heart disease (CHD), and it significantly increases the risk of mortality and other complications and prolongs hospital stay. The underlying mechanisms for the development of thrombosis after cardiac surgery in children with CHD remain poorly understood.

Aim:
To identify novel circulating metabolites before cardiac surgery that are associated with the development of thrombosis in children with CHD after surgery.

Methods:
Untargeted metabolomic data on 1,006 metabolites were measured in plasma from 100 children (age range: 0 days-18 years) with CHD undergoing cardiac surgery. A total of 740 metabolites met quality control criteria (call rate>70% and Spearman correlation coefficient between blind duplicates>0.5). Kruskal Wallis test was used to examine the difference in concentrations of individual metabolites between those who developed thrombosis and those who did not.

Results:
In total, 16 children (16%) developed thrombosis. Among the 740 metabolites, 170 showed differences at a false discovery rate (FDR) of less than 0.01. The top three metabolites showing the strongest associations with thrombosis were 5-methylthioadenosine (MTA), cytidine, and eicosapentaenoate (EPA; 20:5n3) with an FDR of 0.003. Pathway analysis showed that pathways of Arginine biosynthesis (P=7.67х10
-4
), nicotinate and nicotinamide metabolism (P=0.001), and aminoacyl-tRNA biosynthesis (P=0.008) were significantly enriched.

Conclusion:
We have identified promising novel metabolites associated with thrombosis in children with CHD who have undergone cardiac surgery. Replication studies are ongoing.