bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16512: Amputation in Patients With Pad With and Without Diabetes: Insights From the EUCLID Trial
Authors: Govsyeyev Nicholas , Nehler Mark R , Low Wang Cecilia C , Kavanagh Sarah , Hiatt William R , Long Chandler , Jones William S , Fowkes Francis G , Berger Jeffrey S , Patel Manesh R , Katona Brian , Norgren Lars , Bonaca Marc P
Published: May 2021

Background/Introduction:
Amputation is a major morbidity of peripheral artery disease (PAD). Although traditionally attributed to ischemia, the multifactorial nature is increasingly recognized, particularly in those with concomitant diabetes mellitus (DM). Elucidating the drivers of amputation in PAD with and without DM may be important in developing strategies for prevention.

Purpose:
To elucidate the primary drivers of amputations in patients with PAD with and without DM.

Methods:
EUCLID randomized 13,885 patients with PAD. Investigators prospectively reported all amputations. In this post-hoc analysis, amputations (major – ankle and above, minor – distal to ankle) were retrospectively adjudicated using safety data when available to characterize the drivers including infection, ischemia, or multifactorial. Etiologies were evaluated by DM status at baseline.

Results:
A total of 415 patients (3% of total) underwent 533 (260 major and 263 minor) amputations over a median of 30 months. Of these, 360 (68%) occurred in the 5,345 patients with DM (n/N of 6.7%) and 173 (32%) occurred in the 8,450 patients without DM (n/N of 2.0%). There were 172 non-traumatic amputations with sufficient documentation to determine drivers. Ischemia was the primary driver overall (51%) followed by infection (27%) and multifactorial (22%). The primary driver, however, varied by DM status with the dominant driver in those with DM being infection (59%) and in those without DM, ischemia (82%) (
Fig. 1
). The etiology varied for major and minor with the former driven by ischemia (65%) and the latter driven by infection (59%).

Conclusions:
Amputations in PAD appear to have different primary drivers depending on concomitant DM. Infection may have a larger role in those with DM and ischemia in those without DM. Further research to elucidate the pathobiology and predictors of these outcomes may help in the development of strategies for prevention.
Abstract 16519: Meta-analysis of Outcome After Implantable Cardioverter Defibrillator Therapy in Patients With Cardiac Amyloidosis
Authors: Siddamsetti Sisir , Golzy Mojgan , Gautam Sandeep
Published: May 2021

Introduction:
Cardiac amyloidosis is associated with high risk for sudden cardiac death. However, the potential benefit of implantable cardioverter defibrillator (ICD) implantation in CA is unknown due to limited available data regarding outcomes following ICD implantation in this patient population. We sought to perform a meta-analysis of trials that evaluated the outcomes of ICD implantation in CA.

Methods:
We performed a systematic literature review in PubMed, SCOPUS, and Cochrane to identify all studies that evaluated ICD therapy in CA until May 2020. Outcomes analyzed were all-cause mortality and appropriate ICD therapy rates. A random effects model was used to calculate percentages and 95% confidence intervals (CI) of outcomes.

Results:
Of the screened articles, 5 observational studies were included for analysis. A total of 151 patients were analyzed. Mean age of population was 61.6 +/- 0.7 years and 79.2% were male. The all-cause mortality rate was 33% (95% CI:16 to 51%) and the incidence of appropriate ICD therapy was 23% (95% CI:16 to 30%) over a mean follow up period of 16 months (Figure). In trials that evaluated ICD therapy in non-ischemic cardiomyopathy such as DANISH, DEFINITE and SCD-HeFT trials mortality rates in the ICD arm were 21.6 % over 67.6 months, 9.4% over 29 months and 16.7% over 45.5 months, respectively. The incidence of appropriate therapy in DANISH, DEFINITE and SCD-HeFT trials were 28.9%, 19.8 % and 21% respectively.

Conclusions:
CA patients with ICD have equivalent appropriate therapy with disproportionately higher mortality over a shorter follow up compared to randomized trials of primary prevention ICD placement in NICMP. The benefit of ICD placement for mortality reduction in CA remains unclear and further large-scale studies are required to address this issue.
Abstract 16520: Predictors of Thirty Day Readmission in a Vulnerable and Underserved Urban Heart Failure Population
Authors: Steverson Alexandra B , Marano Paul , Chen Caren , Ma Yifei , Stern Rachel , Davis Jonathan D , Hsue Priscilla , Zier Lucas S
Published: May 2021

Introduction:
Heart failure (HF) readmission quality metrics disproportionately impact reimbursement in safety net hospitals. Prior research has demonstrated the effect of medical comorbidities on readmission, however, there is a paucity of data on predictors of readmission in vulnerable and underserved HF patients. We sought to evaluate the effect of demographics, medical and social comorbidities on risk of 30 day readmission in an academic safety net hospital in San Francisco.

Methods:
We performed a retrospective chart review from 2018 to 2020. Patients were included if treated for HF while on inpatient cardiology or medicine services and were assigned an ICD-10 discharge code for HF. Patients less than 21 years old were excluded. Demographics and comorbidities were obtained through evaluation of ICD-10 discharge codes and chart review. Multivariate modeling was used to determine predictors of 30 day readmission.

Results:
The study population included 383 patients in which the mean age was 60±13 years and 73% (n=282) were male. 44% (170) were Black, 23% (88) were Latinx, 33% (127) were not housed, 97% (371) had public insurance, and 21% (81) had a diagnosis of mental illness. 46% (177) had CAD, 76% (291) hypertension, and 36% (177) DM. Substance use was common with 30% (114) using methamphetamines, 36% (138) cocaine, 18% (69) opioids, and 35% (135) alcohol. On multi-variate analysis, EF less than 40% (75%, 285) was the only medical comorbidity associated with an increased risk of readmission (OR 1.86, 1.1-3.1, p= 0.018). Social variables associated with increased risk of readmission included identifying as Black (OR 2.26, 1.03-5.0, p= 0.043) or Latinx (OR 3.43, 1.41-7.59, p= 0.006), homelessness (OR 3.02, 1.76-5.18, p=<0.001), and specific substance use: methamphetamine (OR 2.23, 1.39-3.57, p=0.001), cocaine (OR 1.63, 1.03-2.57, p= 0.037), opioids (OR 1.81, 1.05-3.13, p= 0.033), and alcohol (OR 2.26, 1.43-3.58, p= 0.001).

Conclusion:
Race, housing status and substance use were more strongly associated with readmission risk than medical comorbidities in a population of urban, vulnerable and underserved HF patients. Interventions to improve HF readmission metrics should consider addressing racial and social disparities in similar populations.
Abstract 16526: The Performance of the American College of Cardiology/American Heart Association 2013 Pooled Cohort Equations in Cancer Survivors
Authors: Polter Elizabeth , Blaes Anne , Florido Roberta , Wolfson Julian A , Lutsey Pamela L , Joshu Corinne , Platz Elizabeth , Prizment Anna
Published: May 2021

Introduction:
Cancer survivors may have greater atherosclerotic cardiovascular disease (ASCVD) risk, due in part to cardiotoxic cancer treatments. We tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors.

Objective:
To estimate the calibration and discrimination of PCEs in cancer survivors as compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study.

Methods:
We evaluated the PCEs performance among 992 cancer survivors and 3320 cancer-free participants (controls) who were free of ASCVD (defined as myocardial infarction, coronary heart disease death, or stroke) and did not use statins. Each cancer survivor was incidence-density matched with up to five controls by age (within 5 years), race, sex, and study center. Follow-up started at the index visit: the first study visit that occurred at least one year after the diagnosis date of the cancer survivor (1-17 years after diagnosis) and finished at the ASCVD event, death, or end of follow-up. PCE predictors were measured at the index visit. Calibration of PCEs predictions of 10-year ASCVD risk in cancer survivors and controls was assessed using Hosmer-Lemeshow chi-square tests. Discrimination was measured via Harrell’s C-index.

Results:
54 (5%) and 224 (7%) ASCVD events were observed in 5411 and 22212 person-years among cancer survivors and controls, respectively. Median age was 69 years. 18% were Black. 51% were female. The PCEs overestimated the risk of CVD among cancer survivors as well as controls (Table 1). Discrimination was moderate in cancer survivors (C=0.73) and poorer than in controls (C=0.77).

Conclusions:
The PCEs overestimated ASCVD risk in cancer survivors as well as controls.

Support:
NHLBI, NCI, NPCR
Abstract 16527: Peri-Procedural and 45-Day Outcomes in the Roll-In Cohort of the Amplatzer Amulet Ide Trial of Left Atrial Appendage Occlusion
Authors: Gopinathannair Rakesh , Koerber Scott M , Akella Krishna , Lakkireddy Dhanunjaya
Published: May 2021

Background:
The Amulet IDE trial is an ongoing, randomized, worldwide trial, enrolled but following patients with non-valvular atrial fibrillation (AF) at high risk of stroke. The study is comparing the safety and effectiveness of the Amplatzer™ Amulet™ left atrial appendage (LAA) Occluder to the Watchman device. At US sites, the implanting physicians only had experience with the Watchman device; therefore, up to three roll-in subjects with Amplatzer Amulet device implantation were permitted prior to randomization. The purpose of this analysis is to describe the peri-procedural outcomes for the roll-in cohort.

Methods:
Roll-in subjects met the same eligibility criteria and have the same data collection requirements as randomized subjects. Adverse events were adjudicated by an independent clinical events committee and LAA occlusion was assessed by an independent core laboratory based on the 45-day TEE. Major adverse events included all cause death, ischemic stroke, systemic embolism or device-/procedure-related events requiring open cardiac surgery or major endovascular intervention within 7 days post implant or hospital discharge, whichever is later.

Results:
From August 2016 to November 2018, 201 patients with non-valvular AF at high risk of stroke and bleeding were enrolled at 82 sites as roll-in subjects. Mean age was 74.2 ± 7.5 years and 62% of subjects were male. The Amplatzer Amulet device was successfully deployed in 99% of subjects. Major adverse events within 7 days or hospital discharge occurred in 2.5% of patients and included death (n=3), ischemic stroke (n=1) and vascular access site bleeding (n=1). The majority (79%) of patients were discharged on antiplatelet therapy only or no anti-thrombotic medication. TEE follow-up at the 45-day visit revealed adequate (≤ 5 mm jet) occlusion of the appendage in 98.9% (178/180) of patients. Device-related thrombus (DRT) was identified by the core laboratory in 6 patients (3%); no patient experienced a thrombo-embolic event.

Conclusions:
In the roll-in cohort, with implanting physicians having no prior experience using the Amplatzer™ Amulet™ device, there was a low rate of procedural complications and high rates of both implant success and adequate LAA sealing at follow up.
Abstract 16532: Sedentary Time in Hospitalized Older Adults With Acute Cardiovascular Disease
Authors: Munir Haroon , Goldfarb Michael
Published: May 2021

Background:
Older adults may be subject to prolonged bedrest during hospitalization for acute cardiovascular (CV) disease, which can contribute to poor functional outcomes posthospitalization. Our objective was to describe mobility status in hospitalized older adults with acute CV disease.

Methods:
Patients aged ≥ 60 years old in the cardiac ICU and CV ward at a tertiary care academic centre in Montreal, Quebec were prospectively enrolled from April 2019 to March 2020. Activity levels were measured with an accelerometer (ActiGraph GT9 Link). Sedentary was defined as lying in bed or in a sitting position. Health-related quality of life (HRQoL) was measured with the Short-Form 36 (SF-36) questionnaire by telephone at 1 month post-hospital discharge. The primary outcome was percentage of sedentary time during hospital stay. Secondary outcomes were step counts, steps per minute, and kcal/day consumption.

Results:
There were 35 patients included in the analysis (75.7 6.9 years old; 45.7% females; 22.9% ischemic heart disease; 20.0% heart failure). Patients spent 91.2% ± 5.5 in the sedentary position during their hospital stay (range 80.0-100%;
Figure
). There was no difference in percentage sedentary time by primary diagnosis or sex. Mean steps per minute were 1.0 ± 1.2 and mean kcals consumed per day were 116.6 ± 124.5. In the multivariable analysis, a lower percentage of sedentary time and lower steps per minute were each associated with lower total SF-36 scores at 1-month posthospitalization (both P<0.05).

Conclusion:
Older adults with acute CV disease are sedentary for a large part of their hospital stay. Increased sedentary time is associated with worse self-reported posthospital HRQoL. Future studies are needed to determine whether interventions to increase activity during hospitalization improve posthospital HRQoL and functional outcomes.
Abstract 16533: Heterogeneity of Fibrosis in Patients Undergoing Combined Heart-Liver Transplant
Authors: Rushakoff Joshua , Kransdorf Evan P , Guindi Maha , Patel Jignesh K , Kobashigawa Jon A
Published: May 2021

Introduction:
Combined heart-liver transplant (CHLT) is indicated for patients with end-stage heart failure and concomitant irreversible liver injury. Given that liver dysfunction from congestive hepatopathy is common in patients with end-stage heart failure, it can be difficult to determine reversible from irreversible liver injury. Transjugular liver biopsy (TJLB) is frequently used to evaluate the severity of parenchymal injury, but is limited by heterogeneity of fibrosis across biopsy specimens. We sought to compare the fibrosis evaluation of the TJLB specimens as compared to the pathology of the liver explant at the time of CHLT.

Methods:
All CHLT cases at CSMC between 2007 and 2017 were included. Demographic and liver ultrasound (US) or abdominal computed tomography (CT) imaging was retrieved by chart review. TJLB was performed prior to transplant to determine the severity of liver fibrosis and was compared to the pathology of the liver explant. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns.

Results:
Thirteen CHLTs were performed at our center during the study period. The median follow-up was 59 months (IQR 48-67). Mean age at transplant was 53 years (SD +/- 14.9) and 77% of patients were male. Indications for CHLT included cardiac cirrhosis (7), amyloidosis (2), HCV cirrhosis (2), and congenital heart disease (2). By imaging, 3/7 patients (43%) had US and CT evidence, 2/7 (29%) had US or CT evidence, and 2/7 (29%) had no evidence of liver nodularity US or CT. All patients diagnosed with cardiac cirrhosis had both TJLB and explant pathology for review. All TJLBs were graded as stage 4 fibrosis. Fibrosis on analysis of the liver explant was variable: stage 4 (2), stage 3-4 (3), stage 2-4 (1), and stage 1-4 (1). Thus, 2/7 patients (29%) showed heterogeneity of fibrosis in their explant as compared to their TJLB.

Conclusions:
We found heterogeneity of fibrosis in liver explants of patients that had stage 4 fibrosis (cirrhosis) by TJLB and underwent CHLT. Further work is needed to identify which heart transplant candidates will most benefit from CHLT.
Abstract 16537: Left Atrial Strain in Evaluation of Heart Failure With Preserved Ejection Fraction
Authors: Ye Zi , Miranda William , Yeung Darwin F , Kane Garvan , Oh Jae K
Published: May 2021

Introduction:
Patients with heart failure with preserved ejection fraction (HFpEF) may have elevated left ventricular filling pressure with exercise (LVFP-ex), despite normal LVFP at rest. We aimed to assess the diagnostic value of resting left atrial strain (LAS) in detecting elevated LVFP-ex in dyspneic patients evaluated by exercise stress echocardiography.

Methods:
We performed 2D-speckle tracking analysis for LAS in 669 consecutive patients (mean age 64 ± 14, men 53%) who underwent treadmill echocardiography evaluation and had LV ejection fraction ≥50%. Assessment of LVFP at rest was based on the 2016 ASE Guidelines for diastolic function assessment. We used the 2019 ESC HFA-PEEF diagnostic algorithm to define elevated LVFP-ex (early mitral inflow wave/septal early diastolic tissue velocity (E/e’) ≥ 15 after exercise) and calculate a continuous HFA-PEEF score.

Results:
LAS
reservoir
was lowest in patients with elevated LVFP at rest (n=81) and lower in those with normal resting FP who developed elevated LVFP-ex (n=108) compared to those who maintained normal LVFP-ex (29.0 ± 5.2% vs. 33.1 ± 5.0% vs.39.3 ± 4.8%, p < 0.001). In patients with normal or indeterminate LVFP at rest (n=587), LAS
reservoir
and pre-exercise HFA-PEEF score demonstrated an area-under-the-curve (AUC) of 0.82 and 0.7 respectively for elevated LVFP-ex. There was a 28% higher odds of developing elevated LVFP-ex per 1% decrease in LAS
reservoir
(odds ratio, 95%CI: 0.78, 0.74 - 0.82). In patients with the intermediate score (n=461), 123 patients developed elevation in LVFP with exercise and were classified as having HFpEF per the diagnostic algorithm. Addition of LAS
reservoir
improved the predictive value of HFA-PEEF score for HFpEF (AUC increased from 0.71 to 0.80, p for ΔAUC =0.01).

Conclusions:
LAS
reservoir
has a potential to identify patients at intermediate-risk for HFpEF who may develop elevated LVFP with exercise only, and therefore a promising parameter to aid in the diagnosis of HFpEF when exercise testing is not feasible.
Abstract 16546: Pre-Pregnancy Body Mass Index and Risk of Peripartum Cardiomyopathy and Heart Failure in the Years Following Delivery
Authors: Mints Yuliya , Lyass Asya , Schmiegelow Michelle D , schou morten , Gislason Gunnar H , Christiansen Mia N , Kober Lars , Torp-Pedersen Christian , Andersson Charlotte
Published: May 2021

Introduction:
Peripartum cardiomyopathy (PPCM) is a form of systolic heart failure that occurs during pregnancy or in the early post-partum period. Obesity is known to be associated with other forms of heart failure in young adults, however it is unclear if it is also a risk factor for the development of PPCM.

Objectives:
To investigate the association of body mass index (BMI) with PPCM and heart failure in the years following childbirth.

Methods:
We conducted a retrospective review of pregnant women in the Danish National Patient Registry between 2004 - 2017. Baseline characteristics and other risk factors were obtained at the first prenatal visit (occurring at 8-11 weeks post-conception). Women were followed until the end of the study period, emigration, or death. Logistic regression was performed, adjusting for age as well as other known risk factors for PPCM. Cox proportional hazards analysis was used to assess the long-term risk of development of heart failure.

Results:
There were 403,820 pregnancies evaluated in 300,892 women, with an average age of 29 years. The average BMI was 24.4 kg/m2, with 21.6% classified as overweight (BMI 25 - 30 kg/m2) and 12.8% as obese (BMI > 30 kg/m2). The rate of PPCM was 0.1 per 1,000 in normal weight and overweight groups, and 0.3 per 1,000 in the obese women. After adjustment for age, ethnicity, smoking status, gestational diabetes, and presence of preeclampsia, there was a statistically significant increased risk of the development of PPCM up to 6 months after childbirth in patients who had class I (odds ratio [OR] 2.25, 95% CI 1.08-4.68) but not class II/III obesity (OR 1.63, 95% CI 0.60-4.43). This elevated risk persisted during long term follow up, with hazard ratios of 2.43 (95% CI 1.55 - 3.80) in women with class I obesity and 3.20 (95% CI 1.93 - 5.30) in women with class II/III obesity.

Conclusions:
High early pregnancy BMI is associated with elevated risk of development of peripartum cardiomyopathy even after adjustment for traditional risk factors. This risk of heart failure persists for several years after childbirth.
Abstract 16553: Association Between Family History and Isolated Early-Onset Atrial Flutter Across Race-Ethnicity
Authors: Qiao Victor , Ongtengco Ana , Ornelas Aylin , Chen Yining , Alzahrani Zain , Darbar Dawood
Published: May 2021

Introduction:
There is a genetic predisposition to early-onset atrial fibrillation (EOAF) but the role of family history in the pathogenesis of isolated EO atrial flutter (AFL) across racial and ethnic minorities remains unclear. Here, we determined whether probands with isolated EOAFL across race and ethnicity have a higher rate of AF in first-degree family members than matched control patients with late-onset (LO) AFL.

Methods:
In this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AFL. EOAFL was defined as AFL occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as LOAFL. The main outcome measure was the reported family history of AFL in first-degree relatives.

Results:
Of 106 patients enrolled, 23 (23%) were European American; 53 (52%) were African American, 22 (22%) were Hispanic/Latino (H/L) and 3 (3%) were Asian American. There was a family history of AFL in 11 probands with EOAFL (18%) compared with 3 (7%) patients with LOAFL (Table 1). There was a significantly greater prevalence of CHF in the EOAFL group (40%) than the LOAFL group (21%).

Conclusion:
Probands with isolated EOAFL are more likely to have a first-degree relative with AFL when compared to matched controls with isolated LOAFL. Our findings support genetic predisposition to isolated EOAFL across racial and ethnic minorities.
Abstract 16566: Presentation and Outcome of Pediatric Multisystem Inflammatory Syndrome Temporally Associated With Sars-cov-2 Pandemic: An International Survey
Authors: Bautista Carles , Sanchez-de-Toledo Joan , Bradley Clark C , Herberg Jetrho , Bajolle Fanny , Randanne Paula C , Salas-Mera Diana , foldvari sandrine , Chowdhury Devyani , Bianco Francesco , Singh Yogen , Levin Michael , Bonnet Damien , fraisse alain
Published: May 2021

Introduction:
Following the SARS-CoV-2 pandemic peak, children suffering from a multiorgan inflammatory disease that often leads to shock have been reported. This condition shares features with Kawasaki disease, but its etiopathogenesis is unknown.

Hypothesis:
We aimed to describe presentation and hospital course for this pediatric inflammatory multisystemic syndrome associated with COVID-19 (PIMS-TS).

Methods:
Data were collected from a retrospective review of children from 33 participating European, Asian and American sites.

Results:
We included 183 patients (109 males, 59·6%) with PIMS-TS, at a mean age of 7·0 (±4·7) years. Fifty-six (30·6%) had black ethnicity and obesity was present in 48 (26·2%) cases. Overall, 114/183 (62·3%) had biological evidence of current or recent SARS-CoV-2 infection. At admission, all presented with fever, 117/183 (63·9%) with gastrointestinal symptoms and 79/183 (43·2%) with shock, that was associated with more frequent black ethnicity, higher inflammatory markers and more cardiac involvement. Twenty-seven patients (14·7%) fulfilled criteria for Kawasaki disease. They were younger with no shock, fewer gastrointestinal, cardio-respiratory and neurological symptoms. Among the remaining PIMS-TS patients, 77 (49·3%) had mainly fever and inflammation with less cardiac involvement. For the entire cohort of 183 patients, the mean duration of admission was 8·6 (±5·6) days. Inotropic support, mechanical ventilation and ECMO were indicated in 72 (39·3%), 43 (23·5%) and 4 (2·2%) patients, respectively. Three patients (1·6%) died. A shorter duration of symptoms before admission was a risk factor for worse outcome and for ECMO/death, with 63% increased risk per day reduction (95%CI 0·39-0·93, p=0·03) and with 51·4% increased risk per day reduction (95%CI 0·36-0·9, p=0·03), respectively.

Conclusions:
We describe the first largest international series of children with PIMS-TS. Life-threatening shock is a common presentation. A shorter duration of symptoms prior to admission characterizes the fulminant form of the disease with potentially worse outcome.
Abstract 16587: More Than Five Years After FDA Approval, There Remains Very Limited Adoption of New Evidence-Based, Highly Effective Medications for the Treatment of Patients With Heart Failure, Especially Among Those on Medicare
Authors: Muhlestein Joseph B , May Heidi T , Bair Tami L , Knight Stacey , Knowlton Kirk U , Horne Benjamin D , Le Viet T , Anderson Jeffrey L
Published: May 2021

Background:
Over the past decade, the FDA has approved several new medications that are highly effective when added to existing standard therapy in the treatment of heart failure with reduced ejection fraction (HFrEF). It is possible that, despite the presence of substantial evidence regarding the clinical effectiveness of these new medications, their high cost and the complex medical reimbursement system in America may prevent their routine adoption.

Methods:
We analyzed 5,824 Intermountain Healthcare patients, age ≥18 years with a new clinical diagnosis of HFrEF (LVEF ≤35%), from 1/1/2015 onward, for the use of newly-approved sacubitril/valsartan or any sodium-glucose cotransporter-2 inhibitor (SGLT2-I). We collected baseline characteristics and medication utilization data. We followed the patients for 1.7±1.4 years for future major adverse cardiovascular events (MACE), including death, myocardial infarction (MI), stroke, and heart failure hospitalization (HFH). We identified differences between groups by multivariable Cox regression analysis.

Results:
Baseline characteristics and incidence of MACE, according to insurance status and the use of common HFrEF medications, are shown in the Table. Overall, only 344 (5.9%) and 169 (2.9%) of patients ever received a prescription for sacubitril/valsartan or an SGLT2 inhibitor, respectively. The figures show survival curves for MACE of patients receiving or not receiving the newly-approved medications.

Conclusion:
In this large, modern, real-world HFrEF population, the adoption of newly-approved evidence-based HFrEF medications is minimal in all patients and especially in Medicare patients. This lack of adoption is associated with a significant worsening in patient outcomes. These findings demonstrate a critical need to resolve our present healthcare financial crisis, which is almost certainly the reason for these findings.
Abstract 16588: Using Machine Learning to Improve Survival Prediction After Heart Transplantation
Authors: Ayers Brian , Sandhold Toumas , Gosev Igor , Prasad Sunil , Kilic Arman
Published: May 2021

Introduction:
Prior risk models for predicting survival after orthotopic heart transplantation (OHT) have displayed only modest discriminatory capability. With increasing interest in the application of machine learning (ML) to predictive analytics in clinical medicine, this study aimed to evaluate whether modern ML techniques could improve risk prediction in OHT.

Methods:
Data from the United Network for Organ Sharing registry was collected for all adult patients that underwent OHT from 2000 through 2019. The primary outcome was one-year post-transplant mortality. Dimensionality reduction and data re-sampling were employed during training. The final ensemble model was created from 100 different models of each algorithm: deep neural network, logistic regression, adaboost, and random forest. Discriminatory capability was assessed using area under receiver-operating-characteristic curve (AUROC), net reclassification index (NRI), and decision curve analysis (DCA).

Results:
Of the 33,657 study patients, 26,926 (80%) were randomly selected for the training set and 6,731 (20%) as a separate testing set. One-year mortality was balanced between cohorts (11.0% vs 11.3%). The optimal model performance was a final ensemble ML model. This model demonstrated an improved AUROC of 0.764 (95% CI, 0.745-0.782) in the testing set as compared to the other models (Figure). Additionally, the final model demonstrated an improvement of 72.9% ±3.8% (p<0.001) in predictive performance as assessed by NRI compared to logistic regression. The DCA showed the final ensemble method improved risk prediction across the entire spectrum of predicted risk as compared to all other models (p<0.001).

Conclusions:
An ensemble ML model was able to achieve greater predictive performance as compared to individual ML models as well as logistic regression for predicting survival after OHT. This analysis demonstrates the promise of ML techniques in risk prediction in OHT.
Abstract 16591: The Impact of African Ancestry on the Pooled Cohort Equation Atherosclerotic Cardiovascular Disease Risk Estimation: Insights From the Hispanic Community Health Study/study of Latinos
Authors: Flores Karen P , Khera Amit , Sotres-Alvarez Daniela , Mehta Anurag , Pirzada Amber , Swett Katrina , DAVIGLUS Martha L , C Robert , Engel Gonzalez Pedro , Gallo Linda , Talavera Gregory A , Sofer Tamar , Joshi Parag H , Rodriguez Carlos J
Published: May 2021

ACC/AHA 2018 guidelines recommend using Non-Hispanic (NH)-White pooled cohort equations (PCE) to estimate 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among Hispanics. If African ancestry is present, the PCE for Blacks is recommended. African ancestry estimates among Hispanic Community Health Study/Study of Latinos (HCHS/SOL) background groups have been reported.
1
We applied the PCE based on fractional African ancestry to HCHS/SOL participants and compared risk estimates from NH-White and NH-Black PCE in these groups. HCHS/SOL participants aged 40-75 years were divided into two groups based on median fractional African ancestry of ~10%: groups with >=10% or higher African Ancestry (Puerto Rican, Central Americans, and Dominicans) and those with <10% or lower African ancestry (Mexicans, South Americans, Cubans). Mean predicted ASCVD incidence using both PCE's was assessed. ASCVD risk frequencies are weighted using survey methods. Differences were determined by Rao-Scott Chi-square test. The PCE was applied to 9091 HCHS/SOL participants. (mean age 53.5, 48% F) Applying the NH-White PCE to lower African ancestry groups led to 38% of participants being classified as intermediate/high (>7.5%) ASCVD risk compared to 45% using the NH-Black PCE. Using the NH-White PCE in groups with higher African ancestry led to 36% of participants being classified as intermediate/high risk compared to 46% using the NH-Black PCE. ASCVD risk estimates per Hispanic background groups are shown.
(Figure 1C
). Our study is the first to apply both NH-Black and NH-White PCE to Hispanics and assess differences based on fractional African ancestry. The NH-Black PCE provided consistently greater estimates in both groups with slightly greater differential of estimates relative to NH-White PCE in those with higher African Ancestry. Further studies with outcomes data are needed to determine optimal application of PCE in Hispanics based upon fractional African Ancestry.
Abstract 16593: Secondary Raynaud’s Phenomenon is Associated With Microvascular Peripheral Endothelial Dysfunction
Authors: Sara Jaskanwal Deep S , Taher Riad , Toya Takumi , Lerman Lilach O , LERMAN Amir
Published: May 2021

Introduction:
Previous studies in patients with Raynaud’s phenomenon (RP) have found an association between microvascular abnormalities assessed via nail fold capillaroscopy as well as macrovascular peripheral endothelial dysfunction (PED). However, the association between RP and microvascular PED is not yet established.

Hypothesis:
We hypothesized that patients with RP have greater microvascular PED compared to controls without RP

Methods:
We performed a retrospective cross-sectional analysis of patients referred to Mayo Clinic between 2006 and 2014 for routine cardiovascular evaluation, and who underwent evaluation of Reactive Hyperemia Peripheral Arterial Tonometry (index < 2 consistent with PED). Patients with RP were identified by chart review.

Results:
Six hundred sixty six individuals were included in this study (mean age 51.9±13.5 years, 411 (61.3%) women), 637 (95.1%) individuals did not have RP (control group), and 29 (4.3%) had secondary RP. Only 4 patients had primary RP and were excluded from the final analyses. Individuals with secondary RP had a higher frequency of microvascular PED compared to controls (
Figure
). In a multivariate analysis adjusting for age, sex, smoking status, and use of statins we found a significant association between secondary RP and microvascular PED (OR: 2.45; 95% CI 1.13-5.34; P=0.0236) that remained significant in women after stratifying by sex. In a sensitivity analysis, we compared the frequency of PED in 29 patients with secondary RP and 58 controls matched with respect to age, sex, hypertension, dyslipidemia, and diabetes mellitus. Individuals with secondary RP had a higher frequency of microvascular PED compared to the risk factor-matched controls (18/29 [62.1%] vs 18/58 [31.0%], P=0.01).

Conclusions:
Secondary RP is associated with microvascular PED. Early detection of microvascular PED could help identify individuals with secondary RP who are at risk for developing cardiovascular disease.
Abstract 16624: Gender Disparities Based on Time to Revascularization in the Treatment of Non-st-segment Elevation Myocardial Infarction: An Analysis of 748,439 Nstemi Admissions
Authors: Yerasi Charan , Case Brian C , Wang Yanying , Forrestal Brian , Hahm Joshua , Dolman Sarahfye , Weintraub William S , Waksman Ron
Published: May 2021

Background:
Multiple studies on Non-ST-segment elevation myocardial infarction (NSTEMI) have shown that women tend to have delayed revascularization, with associated worse outcomes, when compared to men. However, there are no studies to date, evaluating the clinical characteristics and outcomes of men versus (vs.) women based on time to revascularization.

Methods:
The study cohort was obtained from the 2016 Nationwide Readmissions Database. We used the International Classification of Diseases, Tenth Revision, to identify patients who underwent diagnostic angiography and subsequently received either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Finally, mortality and 30-day readmissions rates based on gender and time to revascularization were extracted.

Results:
In 2016, there were a total of 748,439 weighted admissions for NSTEMI (57% men and 43% women). Compared to men, women were older and had higher percentage of baseline comorbidities. Women tended to be managed less invasively with only 45% undergoing coronary angiogram as compared to 54% in men (p<0.001). Furthermore, there was a difference in revascularization rates, PCI (men 30% vs. women 21%, p<0.001) or CABG (men 10% vs. women 5%, p<0.001). Majority of men (34%) were revascularized by PCI on same day, while majority of women (30%) were revascularized next-day of admission. In both men and women, patients with more comorbidities tend to have delay in revascularization. Compared to men, in-hospital mortality and 30-day readmission is higher in women as the revascularization is delayed (Figure 1).

Conclusions:
Currently, there exists wide disparity among men and women in the treatment of NSTEMI. Women tend to have worse outcomes as the revascularization gets delayed. Randomized clinical trials are needed to evaluate if a strategy of urgent revascularization (<90 minutes) in women is associated with improved outcomes.
Abstract 16631: Predictors of Left Ventricular Dysfunction in Patients After Anatomic Repair of Congenitally Corrected Transposition of the Great Arteries
Authors: Wilde Megan , Rodenbarger Andrew , Hartog Rebecca , Lim Tiffany , Watkins Kimberly , Lowery Ray , Yu Sunkyung , Afton Katherine , Goldberg Caren S , Lu Jimmy C , Ohye Richard G , Dorfman Adam L
Published: May 2021

Introduction:
After anatomic repair (AR) of congenitally corrected transposition of the great arteries (ccTGA), the left ventricle (LV) is re-established as the systemic ventricle. As such, LV dysfunction is an important factor in long-term patient morbidity. While predictors exist for successful AR, little is known regarding measures of LV function before and after AR, and no known predictors exist of worsening global longitudinal strain (GLS).

Methods:
All patients with ccTGA who survived to discharge after AR at a single institution from 2000-2018 were included. Pre-operative and discharge echocardiograms were reviewed and GLS analysis was performed. LV sphericity index was measured to determine the degree of ventricular septal shift; a lower index denotes more septal bowing into the LV. Logistic regression was used to identify factors associated with worsened GLS after AR.

Results:
Of 91 survivors (65% male), 51 underwent Senning/arterial switch (ASO) and 40 had Senning/Rastelli. Mean LV ejection fraction (EF) decreased from 66% to 61% after AR (p = 0.0003) with 26% having LVEF less than or equal to 55% (increased from 4% pre-op, p = 0.0003). Mean LV GLS was normal pre-op (-20.0% ± SD 4.1%) but worsened following AR (-16.5% ± 4.6%; p <.0001); abnormal LV GLS (> -18%) increased to 62% (vs 32% pre-op, p <.0001). More patients undergoing Senning/ASO (78%) had abnormal LV GLS at discharge compared to those with a Senning/Rastelli (22%) (odds ratio [OR] 9.3, p <.0001). Abnormal pre-op GLS (OR 5.8, p = 0.002) and lower LV sphericity index (OR 1.05, p = 0.01) were also significantly associated with worsening GLS at discharge. In multivariable analysis, all three remained independently associated with worsened LV GLS. Age at AR, ventricular looping, LV posterior wall thickness, and reintervention prior to discharge were not associated with changed LV GLS at discharge.

Conclusions:
Following AR of ccTGA, LVEF decreases but remains in the normal range, while LV GLS detects abnormalities. Risk factors for worsening GLS include abnormal pre-op LV GLS, lower LV sphericity index, and a Senning/ASO repair. Lower LV sphericity index, or more septal shift into the LV, may represent a “less trained” LV, highlighting the need for careful patient selection for AR.
Abstract 16640: Neutrophil Expansion is Essential for Adverse Left Ventricular Remodeling and Dysfunction in Chronic Ischemic Heart Failure
Authors: Antipenko Sergey , Mayfield Nicolas , Jinno Miki , Gunzer Matthias , Prabhu Sumanth D , Rokosh Gregg
Published: May 2021

Chronic inflammation contributes significantly to disease progression in heart failure (HF), and is characterized by expansion of activated macrophages, dendritic cells, and T cells in the failing heart. Neutrophils play a well-known role as the initial drivers of inflammatory response to myocardial infarction (MI), thereby providing the platform for the subsequent recruitment of macrophages and T cells. However, whether and how neutrophils contribute to inflammation and adverse LV remodeling in chronic HF are unknown. We tested the hypothesis that activated neutrophils are required for tissue remodeling and disease progression in HF. Male C57Bl/6 mice were studied 4 and 8 weeks after left coronary artery ligation during established ischemic HF (sham-operated controls). As assessed by flow cytometry, CD11b
+
Ly6G
+
neutrophils were expanded in the peripheral blood (4 w post-MI), and in the bone marrow, spleen, and heart at 8 w post-MI. Immunostaining revealed that in the failing heart, neutrophils were primarily localized to the MI border zone, but also augmented in remote zone myocardium. CXCL1 and CXCL5 chemokine expression was increased in the failing heart, consistent with chemotactic signals for myocardial neutrophil recruitment. Isolated naïve neutrophils also exhibited increased chemotaxis in response to plasma from HF mice (versus plasma from naïve mice), as assessed by time-lapse video microscopy. Moreover, blood neutrophils isolated from HF mice exhibited significantly increased neutrophil extracellular trap (NET) production as compared to control neutrophils, whereas plasma NETs (histone-DNA complexes) were increased in HF mice. Finally, the in vivo role of neutrophils in chronic HF (8 w post-MI) was determined via depletion studies using genetic (Ly6G-diptheria toxin receptor mice) and antibody (1A8) based approaches. In both models, 2 and 4 w of neutrophil depletion, respectively, significantly improved LV systolic function and reduced end systolic volume. 1A8 treated HF mice also exhibited reduced remote zone fibrosis.

We conclude:
neutrophil expansion and activation are important components of the chronic inflammatory response in HF, and play an obligatory role in the progression of LV remodeling in ischemic cardiomyopathy.
Abstract 16644: Durable Septal Pacing Induced by Non-viral Tbx18 Gene Transfer and Tgfβ Inhibition in a Porcine Model of Complete Atrioventricular Block
Authors: Kim Nam Kyun , Lee Ki Hong , Langberg Jonathan , Beyersdorf Jared , Fan Jinqi , Xiao Angel , Fernandez Natasha , Wolfson David , Santangelo Philip , Cho Hee
Published: May 2021

Introduction:
Cardiac pacing can be created by myocardial delivery of TBX18. However, evidence for overt fibrosis at the injection site and the use of viral vectors impede clinical translation of this concept. We hypothesized that non-viral gene transfer of TBX18 combined with prevention of fibrosis with a Tgfβ inhibitor enables durable ventricular pacing in the porcine model of CAVB.

Methods:
All pigs underwent transvenous RF ablation of the AV node to achieve complete heart block on day-1. The pigs were implanted with a backup pacemaker (VVI=50 bpm) and with osmotic pumps designed to release A83-01, an inhibitor of Tgfβ receptors. Synthetic mRNA encoding either TBX18 (n=7) or GFP (n=2) in saline was injected in the high interventricular septum with a NOGA-MYOSTAR™ catheter. Continuous and ambulatory ECG, blood pressure (BP) and activity were recorded for the 4-week study period with telemetry.

Results:
The control pigs were dependent on backup pacing throughout 4 weeks with retrograde conduction from the RV apex. In contrast, TBX18 injected pigs showed higher heart rate (HR) compared to control (4-week mean HR of 58±7 vs 52±7,
p
<0.05), exhibiting antegrade conduction from the high septum with narrow QRS complexes. Max. HR was higher in TBX18 pigs compared to control with a 4-week average of 70±9 vs 55±11 bpm (
p
<0.05). TBX18 pigs exhibited diurnal HR oscillations that directly correlated with their physical activity, indicating chronotropic competence. Likewise, mean BP correlated tightly with mean HR in TBX18 injected pigs (
p
<0.01) but not in control (
p
=0.164), indicating superior hemodynamic measures. Radiopaque agent-enabled, real-time fluoroscopic visualization revealed that the injected biologic spread beyond the intended delivery site in 2 of 7 TBX18 pigs. The mean and max. HR of the 2 pigs were slower than the other five TBX18 pigs, suggesting that conventional imaging can be leveraged to identify redosing criteria, and minimize non-responders. No increase in spontaneous or induced arrhythmias was observed in TBX18 pigs compared to control.

Conclusions:
mRNA delivery of TBX18 combined with Tgfβ inhibition achieved durable septal pacing for 4 weeks in a porcine model chronic heart block, demonstrating therapeutic efficacy with greater safety profiles.
Abstract 16660: Gender Disparities in the Presentation, Management and Outcomes of Patients With Acute Coronary Syndrome: Insights From the Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) Trial
Authors: Khraishah Haitham , Jeong Sun Young , alahmad barrak , Alfaddagh Abdulhamied , Mathenge Njambi , Kassab Mohamad B , KOLTE Dhaval S , Albaghdadi Mazen
Published: May 2021

Introduction:
Despite the increasing interest in sex differences in acute coronary syndrome (ACS) presentation, management, and outcomes in high-income countries, reports on such differences from low- and middle-income countries (LMICs) are limited. Limited resources in LMICs may worsen health disparities experienced by women and vulnerable populations.

Methods:
Using ACS QUIK trial database, we examined sex-differences in terms of baseline characteristics, management received, and relevant clinical outcomes of 21,374 patients presenting with ACS. The main outcomes were the rates of in-hospital and 30-day composite of death, reinfarction, stroke, and major bleeding. We fitted log Poisson multivariate random effects models to obtain the relative risks comparing females to males. We used random intercepts for different hospitals and centers as the clustering variable. Effect measure modification by baseline variables was examined by restricting the analysis to each category and comparing the effect estimates for females to males.

Results:
A total of 5,191 (24.3%) patients were women. Compared to men, women presenting with ACS were older (65±12 vs 58±12 years; p < 0.001), more likely to have hypertension (61.2% vs 42.4%; p < 0.001), and diabetes mellitus (53.5% vs 41.4%; p < 0.001). After symptom onset, women tended to present later to the hospital (medians, 300 vs 238 mins; p < 0.001) and had higher Killip class on presentation (17.8% vs 12.3%; p < 0.001). Women presenting with STEMI were less likely to receive primary PCI (45.9% vs 49.8% of men, p <0.001) and had longer median door-to-balloon times (medians, 90 vs 80 mins for men; p <0.001). Compared to men, women were 53% more likely to experience in-hospital MACE (adjusted RR = 1.53; 95% CI, 1.32-1.77; p<0.001), and 39% higher risk of 30-day MACE (adjusted RR = 1.39; 95% CI, 1.65-2.07, p <0.001).

Conclusion:
In summary, our study confirms a higher CVD risk profile, delayed presentation, suboptimal medical care in women presenting with ACS in Kerala, India. Women were also found to have higher in-hospital and 30-day MACE, even after adjustment for potential confounders.
Abstract 16676: Heightened Platelet Function: An Unrecognized Component of the Covid Hypercoagulability State
Authors: Bliden Kevin , Rout Amit , Chaudhary Rahul , Barnes Jaime , Singh Sahib , Timilsina Saroj , Tantry Udaya , Gurbel Paul A
Published: May 2021

Introduction:
Thrombo-inflammatory syndrome (TIS) characterized by a pathophysiological state of hypercoagulability, heightened platelet function, and inflammation has been observed in patients with acute myocardial infarction, and HIV.

Hypothesis:
The incidence of TIS is observed at a high rate in COVID-19 patients and worsens with symptom severity

Methods:
Blood samples from COVID-19 positive hospitalized patients (n=24) was collected for coagulation and platelet function analysis using point-of-care thromboelastography, TEG6s (Haemonetics, Corp) and routine labs were collected to measure markers of inflammation, coagulation, and organ damage (Table). Disease severity was grouped according to oxygen supplementation requirements and comparisons were made using unpaired t-test and chi-squared tests. Thrombo-inflammation was defined as the presence of both hypercoagulability by TEG [Clot initiation (R) < 4.6, fibrin clot strength (FCS) >32mm, and platelet fibrin clot strength (PFCS) >69] and D-dimer >ULN.

Results:
Ninety- five percent of COVID positive patients had at least one co-morbidity with the incidence of hypertension (71%), diabetes (50%), and obesity (42%) being the most frequent. A total of 63% (16/24) of patients had TIS, the incidence was significantly increased with escalating disease severity (p=0.03). A significant stepwise (p<0.05) increase in FCS, D-Dimer, WBC count, lactate dehydrogenase, and procalcitonin was observed with worsening respiratory function (table). MA-ADP a measure of platelet function was in the high normal range for 81 % of patients.

Conclusions:
Thrombo-inflammatory is observed with most COVID patients, importantly heightened platelet function is a component of the syndrome and raises the question if antiplatelet therapy is needed in select COVID patients. Selective assessments with TEG6s may facilitate antithrombotic personalization.