bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15930: Circulating Levels of Proprotein Convertase Subtilisin/kexin Type 9 (pcsk9) are Associated With Monocyte Subsets in Patients With Stable Coronary Artery Disease
Authors: Krychtiuk Konstantin , Lenz Max , Hohensinner Philipp , Distelmaier Klaus , Schrutka Lore , Kastl Stefan , Pfaffenberger Stefan , Huber Kurt , Hengstenberg Christian , Wojta Johann , Speidl Walter S
Published: November 2020

Introduction:
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis. Circulating monocytes can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets.

Methods:
We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM).

Results:
Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n=55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p=0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R=0.29; p=0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p=0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p=0.05). Conversely, patients with PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p=0.02). In contrast, IM showed no association with PCSK-9 levels.

Conclusions:
We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.
Abstract 15942: Oral Anticoagulation as Compared to Oral Anticoagulation Plus Single Antiplatelet Therapy in Stable Coronary Artery Disease With Af: A Meta-analysis
Authors: Vaz Igor , Kumar Ashish , Shariff Mariam , Doshi Rajkumar P , Duarte Rafael
Published: November 2020

Introduction:
There are limited data on the appropriate antithrombotic therapy in patients with stable coronary artery disease (CAD) and concurrent atrial fibrillation (AF). The efficacy of using a single antiplatelet (SAP) in addition to oral anticoagulation (OAC) as compared to OAC alone remains controversial, with the earlier regimen associated with increased risk of major bleeding.

Methods:
A systematic electronic search of the PubMed, EMBASE and Cochrane databases was performed to identify relevant publications. Inclusion criteria were randomized controlled studies (RCTs) and observational studies comparing OAC+SAPT to OAC alone in patients with stable CAD and concurrent AF. All-cause mortality, stroke and myocardial infarction (MI) were the endpoints analyzed. We used the inverse variance method with random-effect model to calculate the hazard ratio (HR) with 95% confidence interval (CI). Statistical heterogeneity was calculated using Higgins I2 statistics. All statistical analysis was performed using RevMan Version 5.3.

Results:
The final analysis included two RCTs and 3 observational studies comparing OAC+SAPT versus OAC alone in patients with stable CAD and AF. There was no difference in the rate of mortality between the two treatment strategies [HR: 1.13, 95%CI: 0.88-1.46, I2= 71%] [Figure, PANEL A]. Subgroup analysis based on RCTs and observation studies reported similar results. Additionally, there was no difference in the rate of stroke [HR: 1.24, 95%CI: 0.83-1.85, I2= 0%] [Figure, PANEL B]or MI [HR: 0.57, 95%CI: 0.29-1.14, I2= 0%] [Figure, PANEL C] between the two treatment strategies

Conclusion:
OAC+SAPT as compared to OAC alone in patients with stable CAD and AF was associated with similar rates of all-cause mortality, stroke and MI.
Abstract 15946: The Impact of COVID-19 on Blood Pressure Trends Utilizing a National Remote Monitoring Platform
Authors: Peterson Eric D , James Roberta A , Barrett Malcolm , Schnieder Jennifer , Shah Bimal R
Published: November 2020

Background:
The Shelter-in-place response to the COVID-19 pandemic has demonstrated the value of telemedicine and remote monitoring platforms like Livongo’s Home Blood Pressure Monitoring Program (HBMP) that utilizes a Bluetooth connected blood pressure cuff and access to coaches. The objective of this study was to understand the HBPM frequency and blood pressure trends during the pandemic for this high-risk group of people.

Methods:
Utilizing Livongo’s national repository of HBMP participants, we selected members with valid measurements between September 16, 2019 and June 15, 2020. The COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University was used to identify the first date a COVID-19 case was identified in each state and county. The top 9 counties with the highest cumulative COVID-19 cases were selected for further evaluation. Weekly national, regional, state, and county number of BP checks, mean SBP and DBP readings, and percentage of people with BP >= 130/80, >=140/90, and >= 160/100 were evaluated.

Results:
There were 47,745 HBPM participants, age of 54 year, 47% female, mean baseline BP of 129/79. The national trend showed slight increases in SBP and DBP during March 2020 though BP monitoring frequencies seem unchanged. Figure 1 shows state SBP and DBP trends by region. Some of the variability in the states is due to top counties with cases. Cook County, IL had a mean (95% CI) SBP increase of 6.5 mmHg (7.8, 5.1) resulting in while New York City's mean SBP decresed to -1.4 mmHg (-0.1, -2.7).

Conclusion:
There is a lot of variation in regional trends on the impact of COVID-19 on BP, even for the 9 selected counties. Further study is required to understand the possible drivers of the trends, such as, medication adherence, exercise, and stress.
Abstract 15949: Post-transcriptional Regulation of Cardiac Pathological Remodeling-- Role of Cytosolic Rbfox1c
Authors: Gao Chen , xiong Zhaojun , Liu Jianfang , Wang Menglong , Hsiao Yun-Hua , Ren Shuxun , Rau Christoph D , Li Katelyn , Vondriska Thomas M , Wang Yibin , Xing Yi
Published: November 2020

Post-transcriptional regulation plays a key role in transcriptome reprogramming during cardiac development and pathogenesis. In previous study, we have identified that loss of RBFox1 is a molecular hallmark associated with cardiac pathological hypertrophy and heart failure. We further demonstrate that RBFox1 regulates cardiac gene expression and function at post-transcriptional level through targeted RNA splicing in nuclei. However, RBFox1 gene also generates a cytosolic isoform RBFox1c, suggesting that it might also regulate other aspects of post-transcriptional regulation in heart. We detected that RBFox1c mRNA constituted 40% of total RBFox1 level in normal adult heart but repressed in diseased heart. In RBFox1-cKO mice, enhanced cardiac fibrosis was associated with loss of cardiac function following MI or TAC. Restoration of RBFox1c expression (RBFox1c-TG) significantly reduced cardiac fibrosis. RNA sequencing in RBFox1c expressing cardiomyocytes showed that RBFox1c specifically suppressed the expression of pro-inflammatory genes. The pro-inflammatory genes were induced in the RBFox1 deficient hearts but suppressed upon cardiomyocyte specific RBFox1c expression. In vitro, RBFox1c expression in NRVM suppressed PE induced proinflammatory genes and significantly blocked the effects of the conditioned media on fibroblast proliferation. De novo motif discovery identified a significant enrichment of the conserved RBFox1 binding motif in the 3’UTRs of the RBFox1c dependent genes. RNA-CLIP analysis further demonstrated a direct binding of RBFox1c to the pro-inflammatory gene 3’UTR. We characterized the interactome of RBFox1c and found RBFox1c specifically interacted with a component of the RNA non-sense mediated decay machinery-Upf1. RBFox1c interaction with Upf1 in cardiomyocytes was diminished upon hypertrophic stress. By inactivation of Upf1 via siRNA, we demonstrated that RBFox1c mediated repression of proinflammatory genes was Upf1 dependent. Finally, by temporally induced expression of RBFox1c in post-TAC heart, we provided proof-of-concept evidence that targeted expression of RBFox1c was sufficient to ameliorate pathological remodeling and progression of heart failure as a potential gene-based therapy.
Abstract 16247: Methamphetamine Use Predicts Worse Prognosis in a Safety Net Heart Failure Population
Authors: Thakkar Anjali B , Ma Yifei , Wang Teresa , Teng Alexandra , Scherzer Rebecca , Hsue Priscilla
Published: November 2020

Background:
Methamphetamine (MA) use is rising, and overdose deaths have increased by 500% in San Francisco since 2008. MA use is associated with heart failure (HF); yet, cardiovascular (CV) outcomes in this population have not been described.

Methods:
We performed a retrospective case-control study of HF patients at a safety net hospital in San Francisco. Between January 2001-June 2019, 1771 HF patients with MA use were matched by age and gender to 3542 HF patients without MA use. We examined age and gender-adjusted associations of MA use with likelihood of index HF admission and 30-day readmission (HF and all-cause), and used demographic-adjusted Cox regression model with competing risks to compare hazard rates associated with MA use over the 18-year study period.

Results:
At time of HF diagnosis, mean age was 52 years and 77% were male. Patients with MA use were significantly more likely than non-MA users to be black (49.1% vs 33.0%), and to have comorbid conditions including HIV (14.5% vs 4.7%), pulmonary hypertension (11.1% vs 7.7%), hypertension (82.0% vs 77.6%), and cocaine use (58.0% vs 14.7%). Despite similar rates of coronary artery disease, myocardial infarction, and diabetes, HF patients with MA use were less likely to have percutaneous coronary intervention (6.1% vs 8.2%) or coronary artery bypass graft (0.8% vs 1.4%), p<0.05 for all. Compared to HF patients without MA use, HF patients with MA use had higher rates of index HF hospitalizations (36.0% vs 21.7%, adjusted odds ratio 2.04, 95% CI 1.80-2.32, p<0.01), 30-day HF readmission (12.2% vs 6.4%, adjusted hazard ratio (aHR) 1.87, 95% CI 1.31-2.67, p<0.01) and 30-day all cause readmission (20.9% vs 14.3%, aHR 1.46, 95% CI 1.14-1.88, p<0.01). Exposure to MA was associated with higher likelihood of death during the study period, regardless of hospitalizations (22.4% vs 15.1%, aHR=1.17, 95% CI 1.03-1.33, p<0.01).

Conclusions:
In our study, HF patients with MA use were more likely to be admitted for an index HF admission; subsequently, they were also more likely to be readmitted within 30 days. Regardless of hospitalization risk, individuals with MA use had higher likelihood of death. Further study to understand the clinical and socioeconomic factors driving worse outcomes in this high-risk population is needed.
Abstract 16257: Giant Left Circumflex (LCx) Coronary Artery Aneurysm (CAA) Presenting as a Cardiac Mass
Authors: Aljamal Ahmad O , Raad Mohamad , Parikh Sachin
Published: November 2020

Introduction:
CAAs are a rare but potentially life-threatening condition. Commonly defined as localized dilations greater than 1.5 times the adjacent artery, “giant” CAA (GCAA) is a term used to describe CAAs that have progressed to greater than four times the adjacent artery.

Case:
A 73-year-old male who presented with acute dyspnea was found to have a 4.5cm epicardial mass on computed tomography angiography (CTA) of the chest. Coronary angiography revealed a large partially thrombosed saccular aneurysm of the proximal LCx with diffuse ectasia of the remaining coronary arteries. He underwent percutaneous coronary intervention (PCI) with the placement of a covered stent from the left anterior descending to the left main artery, traversing and effectively occluding the LCx. He tolerated the procedure and was discharged on clopidogrel and apixaban.

Discussion:
Due to their insidious nature, CAAs are underdiagnosed and progress undetected. Serious complications include aneurysm rupture and fistula formation. CAAs are most commonly caused by atherosclerosis but have been associated with infectious, rheumatologic, and genetic etiologies. Drug-eluting stents are increasingly implicated in CAAs by the mechanism of direct vessel trauma and drug-induced inhibition of smooth muscle proliferation. The optimal management of CAAs remains unclear. Cardiovascular risk reduction and monitoring are recommended. Invasive management is usually reserved for giant or unstable aneurysms. Surgical resection or repair is conventional but percutaneous methods such as coiling and stent occlusion are increasingly utilized. Our patient underwent a successful vessel and aneurysm occlusion with favorable post-PCI outcomes.

Conclusion:
GCAAs are extremely rare and understudied. Percutaneous management appears effective in the management of GCAAs, but the study of long-term safety and outcomes is required.
Abstract 16267: Coronary Artery Bypass Grafting versus Percutaneous Coronary Intervention in Patients Presenting With Acute Coronary Syndrome With Culprit Unprotected Left Main Artery
Authors: Barssoum Kiro , Kumar Ashish , Rai Devesh , Kharsa Adnan , Chowdhury Medhat , Thakkar Samarthkumar J , Rao Mohan
Published: November 2020

Background:
Outcomes of coronary artery bypass grafting (CABG) versus (vs) percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndromes (ACS) with unprotected left main (ULM) as culprit vessel are not well represented in major clinical trials. We performed a meta-analysis and meta-regression of studies that compared the outcomes of CABG vs PCI in ULM in ACS.

Methods:
Medline, EmCare, CINHAL, Cochrane database, and Google Scholar were searched for studies comparing CABG vs PCI in patients who presented with ACS and was found to have ULM as culprit vessel. Our primary outcome was mortality at longest follow up. Our secondary Outcome was repeat revascularization at longest follow up. We used PM method with HKSJ adjustment to estimate risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using I
2
statistics. Multivariable meta-regression analysis was used to account for heterogeneity. History of smoking, diabetes, hypertension and previous PCI was used for multivariable regression. R version 3.6.2 was used for all statistical analysis.

Results:
A total of 8 studies met our inclusion criteria. The follow up period varied from 6 months to 10 years. There was no significant difference in the risk of mortality between CABG vs PCI; RR: 1.31, CI: 0.76 - 2.27, I
2
= 71%. However, the PCI as compared to CABG was associated with higher risk repeat revascularization at longest follow up; RR: 2.64, 95% CI: 1.56 to 4.46, I
2
= 60%. Meta-regression analysis reported previous PCI to be associated with lower mortality with CABG [P value =0.01], while history of diabetes was associated with higher mortality with CABG [P value <0.001].

Conclusion:
CABG vs PCI in ULM in ACS is associated with similar risk of mortality. Previous PCI and non-diabetics were associated with higher mortality with PCI as compared to CABG. However PCI as compared to CABG was associated with higher risk of repeat revascularizations.
Abstract 16269: Does the “July Effect” Impact Heart Failure Outcomes? A Real-World Analysis of More Than Half a Million Nationwide Admissions
Authors: Kolkailah Ahmed A , Abougergi Marwan , Desai Parth V , Patel Axi , Fugar Setri , Okoh Alexis K , Al-ogaili Ahmed , Hirji Sameer , Kaneko Tsuyoshi , Volgman Annabelle S , Doukky Rami
Published: November 2020

Background:
The “July effect” is a well-described phenomenon in academic medicine, relating to the annual influx of new trainees. We examined whether the “July effect” impacts inpatient outcomes of admissions for heart failure (HF).

Methods:
Between 2012 and 2014, we included adult patients (≥18 years) with a primary diagnosis of HF, defined using ICD-9 codes, from the National Inpatient Sample. We excluded non-teaching hospitals. Primary endpoint was in-hospital mortality. Secondary endpoints included hospital length of stay (LOS) and total cost adjusted for inflation. Logistic regression and adjusted odds ratio (OR) were used to adjust for confounders. Based on academic calendar, we classified admissions into 4 quarters (Q1-4). Q1 and Q4 were designated to assess the effect of novice (July effect) vs. seasoned trainees, respectively.

Results:
We identified 699,675 HF admissions during Q1 and Q4 over the study period. Mean age was 71 years and 48% were females. There were 20,270 in-hospital deaths (Q1 9,695 vs. Q4 10,575). After adjusting for confounders, there was no mortality difference between Q1 and Q4 admissions; adjusted OR 0.96, p = 0.23 (Figure). Similarly, there was no difference in hospital LOS or total cost; 5.8 vs. 5.8 days, p = 0.66 and $13,755 vs. $13,586, p = 0.46, in Q1 and Q4, respectively.

Conclusion:
In the largest study to date, there was no evidence of a “July effect” on inpatient HF outcomes. This may be credited to the well-defined guidelines which facilitate safe patient care in these patients.
Abstract 16273: Safety of Subcutaneous ICD Implantation in Patients With Prior Sternotomy
Authors: AlKofahi Mejalli , Mohammed Moghniuddin , Reddy Madhu , Dendi Raghuveer , Pimentel Rhea C , Berenbom Loren D , Emert Martin , Ramirez Rigoberto , Noheria Amit , Sheldon Seth H
Published: November 2020

Introduction:
Subcutaneous ICD (S-ICD) implantation is a viable alternative to transvenous ICD implantation in patients without a pacing indication. The S-ICD lead is placed near the sternum. The safety of S-ICD implantation and risk for inappropriate shocks is uncertain in patients with prior sternotomy.

Methods:
This single-center retrospective cohort study included patients that had implantation of an S-ICD between February 2014 - May 2020. The 30-day complication rates and long-term risks of inappropriate shocks were compared between patients with and without prior sternotomy.

Results:
Ninety-eight patients (52 ± 15 years old, 43% men, BMI 29 ± 6, 72% primary prevention, 28% ischemic cardiomyopathy, median LVEF 30% (IQR 25-45%)) underwent S-ICD implantation, among whom 19 (19.4%) had a prior sternotomy. The median time between sternotomy and S-ICD implantation was 96 (IQR 4.1-306) months. The sternal coil was primarily implanted left of the sternum (n=17/19, 89%). A two-incision technique was used in 79% of patients with prior sternotomy vs. 65% without sternotomy (p=0.23). The 30-day complication rate was similar between those with and without prior sternotomy (n=1/19 vs. n=10/79, 5% vs. 13%, p=0.36). The only 30-day complication in patients with prior sternotomy was a hematoma without intervention. The 30-day complications in patients without prior sternotomy included: superficial site infection resolving with brief antibiotics (n=4), inappropriate shock (n=3), lead migration requiring revision (n=2), and a hematoma without intervention (n=1). Over a median follow-up of 17.1 (IQR 3.4-29.1) months, the frequency of inappropriate shocks was similar between patients with and without prior sternotomy (n=1/19 and n=6/79, 5% vs. 8%, p=0.72). The median time to inappropriate shock from S-ICD implantation was 1.1 (IQR 0.1-19.8) months. The mechanisms of inappropriate shocks were T-wave oversensing or other oversensing (n=5/7, 72%), air in the pocket (n=1/7, 14%), and atrial tachycardia (n=1/7, 14%).

Conclusions:
Implantation of S-ICD in patients with prior sternotomy was not associated with an increased risk of 30-day complications or inappropriate shocks. These outcomes need to be confirmed in larger, multicenter studies.
Abstract 16274: Risk of Bleeding in Patients With Non-Valvular Atrial Fibrillation Exposed to Apixaban With or Without Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-norepinephrine Reuptake Inhibitors (SNRIs)
Authors: Shen Sophie W , Jiang Jenny , Priyadarshi Ankit , Zhang Guoqiang
Published: November 2020

Background:
Patients with NVAF treated with direct oral anticoagulants (DOACs) are often also treated with SSRI/SNRI for co-existing conditions. Whether the concomitant use of SSRI/SNRI with DOAC such as apixaban would impart additional bleeding risk over that of apixaban alone has not been well studied.

Objective:
To assess the risk of major bleeding (MB) in patients with NVAF treated with apixaban alone and in concomitant with SSRI/SNRI in a real-world setting.

Methods:
We identified patients with NVAF, and newly prescribed with apixaban or co-administered with SSRI/SNRI (Apix+SSRI/SNRI) in a large US administrative claims database (1JAN2013-31DEC2017). Patients treated with Apix+SSRI/SNRI were matched by propensity score (PSM) with those treated with apixaban only. Cox model was used to estimate the hazard ratios (HRs) of overall and individual MB (GI bleeding, intracranial hemorrhage [ICH], or other bleeding requiring hospitalization) across matched cohorts. Additionally, we applied inverse probability treatment weighting (IPTW) and covariates balancing PS (CBPS) methods to adjust for unbalanced covariates despite matching on PS.

Results:
We identified 32,225 and 6,101 patients with NVAF newly prescribed with apixaban and co-administered with Apix+SSRI/SNRI. Before PSM, Apix+SSRI/SNRI patients were older, had higher baseline CHA
2
DS
2
-VASc and HAS-BLED scores, more comorbidities, and received a lower dosage of apixaban. PS matched 6,035 patients in each group. The adjusted HR (95% CI) of overall MB, with Apix+SSRI/SNRI relative to apixaban alone was 1.42 (0.94-2.15). For GI bleeding HR was 1.26 (0.74-2.15), 3.94 (0.78-19.77) for ICH, and 1.39 (0.66-2.93) for other bleeding leading to hospitalization. The estimated associations between co-administration of apixaban with SSRI/SNRI and MB were less strong with IPTW and CBPS analyses. None of the HR point estimates was statistically significant.

Conclusion:
In this real-world study of patients with NVAF, patients co-administered with apix+SSRI/SNRI did not show significant increased risks of MB compared with those on apixaban alone. The findings do not suggest apixaban used concomitantly with SSRI/SNRI would impart additional risk of MB over that of apixaban alone in patients with NVAF.
Abstract 16278: Discordant Lipid Phenotype and Other Determinants of Statin Response in the Pravastatin Inflammation/crp Evaluation (PRINCE) Trial
Authors: Ajala Oluremi N , Demler Olga , Liu Yanyan , Ridker Paul M , Glynn Robert J , Chasman Daniel , Mora Samia
Published: November 2020

Introduction:
Wide variability in LDL-C change is observed with statins, yet determinants of statin response are uncertain.

Methods:
Participants were selected from the primary prevention cohort of the Pravastatin Inflammation/CRP Evaluation double-blind trial that randomized participants to pravastatin 40 mg/d or placebo over 24 weeks. Baseline and 24-week levels of LDL-C and 15 other biomarkers were measured in 495 participants. We defined optimal statin response as >=30% LDL-C reduction and suboptimal response as <30% reduction. Sub-optimal hs-CRP response was defined as >=median (14%) decline in hs-CRP from baseline to 24 weeks and non-response as no decrease or an increase in hs-CRP. χ
2
, t-tests and ANOVA were used to compare variables across optimal statin response (N=166) and suboptimal response (N=287). Multivariable logistic regression models evaluated associations of determinants of statin response. Forward selection identified variables that associated with response. Xgboost was used to train and validate the models using 2/3 and 1/3 of the data respectively.

Results:
Significant determinants of optimal statin response included older age, and higher baseline levels of LDL-C and triglyceride-rich lipoproteins. By contrast, female sex, alcohol intake >=1 drink/day, diabetes, higher baseline levels of apo B and lipoprotein(a) were associated with decreased response, as was hs-CRP non-response (Table). Race, baseline hs-CRP and sub-optimal hs-CRP response, smoking, HDL-C and BMI had no significant effect on statin LDL-C response. Training and validation of models predicted suboptimal LDL-C response with an AUC of 0.71. Similarly, training and validation of models using Xgboost yielded an AUC of 0.85.

Conclusion:
This study identified discordant lipid phenotype and other determinants of moderate-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.
Abstract 16296: Heart Failure-Smart Life: Effects of a Mobile-based Education and Self-management Program for Patients With Heart Failure
Authors: Ahn Jeong-Ah , Choi Eui-Young , Park Jin-Sun
Published: November 2020

Introduction:
It is considered an important strategy to support heart failure (HF) patients for lifetime self-management. However, some programs for HF patients made them difficult to revisit the hospital or due to economic burden. Therefore, a practical alternative to a comprehensive and user-friendly self-management program for HF patients is needed.

Purpose:
The aim of this study was to develop a mobile App program for HF patients, and to identify the impact of the program on patients with HF.

Methods:
We developed a mobile App program, named “HF-Smart Life”. This App installed the configurations and functions of educational materials using pictures and animations, daily health (blood pressure and body weight) check-up diary, Q & A, and 1:1 chat considering user’s convenience. Regarding the experimental study, we employed a quasi-experimental design to evaluate the effects of the program in 74 patients with HF. The experimental group participated to use the mobile App program, including education, feedbacks on self-management, and monitoring in their daily life, for 3 months.

Results:
Participants of the program (n=36) exhibited significantly improved NYHA functional class and cardiac diastolic function (E/Ea ratio measured by echocardiogram) than the control group (n=38) after 3 months. The mean NYHA function class of the experimental group changed from 2.14 to 1.82, and that of the control group changed from 2.66 to 2.38 (F=9.260, p=.003). Also, the mean E/Ea ratio decreased from 12.24 to 11.35 in the experimental group, whereas that of the control group increased from 14.70 to 16.42 (F=5,280, p=.024). However, there was no significant difference between the groups with cardiac systolic function (left ventricular ejection fraction measured by echocardiogram) and quality of life.

Conclusions:
This mobile App program showed effectively improvements in HF patients' symptom (functional) class and cardiac diastolic function. Future study is needed to investigate the long-term effects of the mobile-based education and self-management program in HF population.

Funding:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2017R1C1B1007090 & 2019R1F1A1063148).
Abstract 16300: Preoperative Computed Tomography Angiography Reveals Leaflet-specific Contribution to Aortic Stenosis Influenced by Local Coronary Factors
Authors: Chen Ian Y , Vedula Vijay , Malik Sachin B , Liang Tie , Chung Kieran S , Sayed Nazish , Tsao Philip S , Giacomini John C , Marsden Alison L , Wu Joseph C
Published: November 2020

Background:
Current computed tomography (CT)-based diagnosis of severe aortic stenosis (AS) using aortic valve calcification (AVC) load does not take into account interleaflet differences in calcification and leaflet dysfunction.

Objectives:
We sought to assess the functional impact of these differences and identify factors that can influence calcification load in a leaflet-specific manner.

Methods:
We retrospectively reviewed the CT angiograms (CTA) of 170 AS patients being considered for valvular intervention and 20 control normal-valve patients. We quantified AVC load, aortic valve leaflet calcification (AVLC) load, and systolic leaflet excursion (LE
sys
), and used regression analysis to investigate their interrelationships. We further performed computer simulation to examine how interleaflet differences in LE
sys
affect aortic valve area (AVA). Lastly, we used regression analysis to identify contributors of leaflet-specific calcification.

Results:
We observed significant interleaflet differences in AVLC load in AS patients, with noncoronary cusp (NCC) carrying the most load (342.0 [220.3-603.1] AU), compared to the right coronary cusp (RCC) (278.5 [168.2-492.1] AU;
P
< 0.001) and the left coronary cusp (LCC) (240.6 [143.1-450.3] AU;
P
< 0.001). However, LCC, but not NCC, was associated with the least LE
sys
(43.0 [38.4-49.2] °), compared to both NCC (45.2 [41.2-49.9] °;
P
= 0.009) and RCC (47.8 [42.1-53.0] °;
P
< 0.001). Computer simulation of normal valve dynamics revealed that NCC and RCC contributed 10.4 [-1.6-15.7] % more (
P
= 0.004) and 10.7 [4.9-20.4] % more (
P
< 0.001) to AVA than LCC. In multiple regression analysis, only NCC and RCC AVLC loads predicted LE
sys
(b = -0.015,
P
< 0.001; b = -0.020,
P
< 0.001), but not LCC AVLC load (b = -0.008;
P
= 0.065). Both ostial/proximal occlusion and ostial height of right coronary artery predicted RCC AVLC load (b = 71.508,
P
= 0.007; b = 10.252,
P
= 0.008).

Conclusions:
NCC and RCC should be given more weight than LCC in the evaluation of AS because of their greater AVC loads, more predictable LE
sys
-AVLC relationships, and greater contributions to AVA. Ostial/proximal occlusion and large ostial height of RCA should signify risk for disease progression in RCC.
Abstract 16309: Age Specific Baseline Predictors of All-cause Mortality in Systolic Blood Pressure Intervention Trial (SPRINT) Identified by Machine Learning
Authors: Gani Nuha , Husain Anwar , Dandi Gauri , Atkinson Ian , Mallick Zyannah , Banerjee Avantika , Xin Victoria , Hayashi Scout , Lewis Natalie , Mahmood Nayab , Hasan Noah , Qureshi Khizar , Dey Amit , Rosenberg Yves D , Hasan Ahmed A
Published: November 2020

Introduction:
The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT01206062) aimed to identify an SBP target to reduce incidence of cardiovascular (CV) morbidity and mortality in hypertensive, non-diabetic patients of age ≥ 50 at increased CV risk. It found that intensive treatment (SBP target <120 mmHg) led to fewer major CV events and death but higher rates of adverse events. We reused publicly available patient-level SPRINT data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF), to identify age specific baseline (bl) predictors for all-cause mortality (ACM).

Methods:
RSF was performed on 30 bl variables from 9361 patients in age group specific cohorts (50-59, 60-69, 70-79, 80-90). The identified top 10 predictors from each cohort were included in a multivariate analysis using a Cox proportional hazards model.

Results:
The top 10 predictors of ACM for age specific subgroups are shown in Figure 1. As expected, cardiovascular disease (CVD) predictors were selected, yet RSF distinctively identified renal biomarkers as important predictors, consistent with our previous analyses. Smoking status and history of CVD ranked as top predictors among age groups 50-59, 60-69, and 70-79. RSF also identified social factors, including race among age groups 60-69 and 80-90 and female gender among age groups 50-59 and 80-90 as important predictors for ACM. Lipid markers and medications used also showed up as top predictors. Specifically, polypharmacy emerged as a top predictor in age groups 60-69, 70-79, and 80-90, notably ranking higher in the 80-90 age group.

Conclusions:
Using ML, we uncovered in an unbiased fashion, unanticipated age specific top predictors for ACM in SPRINT trial. This highlights the value of ML for analyzing disease and therapeutic intervention outcomes and age specific prognostic factors to advance precision medicine.
Abstract 16311: Efficacy and Safety of Inclisiran According to Sex: A Pooled Analysis of the ORION 9, 10 and 11 Trials
Authors: Wright R Scott S , Ray Kausik K , Raal Frederick J , Kallend David , Jaros Mark , Koenig Wolfgang , Leiter Lawrence , Landmesser Ulf E , Schwartz Gregory G , Wijngaard Peter L , Kastelein John J ,   for the ORION Phase III investigators
Published: November 2020

Introduction:
Despite a later onset in life than males, ASCVD is the leading cause of death in females, additionally mortality is higher compared to males. Disparities in the diagnosis and treatment of CVD risk factors may contribute to this difference. Inclisiran is a novel siRNA that inhibits PCSK9 synthesis and lowers LDL-C. Three Phase III placebo-controlled trials evaluated efficacy and safety of inclisiran in patients with HeFH (ORION-9), ASCVD (ORION-10, -11) and ASCVD risk equivalents (ORION-11).

Objective:
To assess the impact of sex on the efficacy and safety profile of inclisiran.

Methods:
Patients from each trial were categorized by sex. The co-primary endpoints were percentage change in LDL-C from baseline to Day 510 and time-adjusted percentage change in LDL-C from baseline after Day 90 up to Day 540. Secondary efficacy and safety parameters were assessed over 18 months.

Results:
Of a total 3660 patients, 1190 (32.5%) were females and 2470 (67.5%) were males. At baseline, females were less likely to receive statins [high-intensity statins] (90% [70%]
vs
93% [76%]), or have ASCVD (73.6% vs 90.3%), were more likely to have ASCVD-risk equivalent (26.4%
vs
9.7%)
vs
males. The efficacy of inclisiran
vs
placebo in both co-primary endpoints was similar in both sexes. Females had higher LDL-C at baseline (122.9 mg/dL
vs
105.8 mg/dL) and (secondary endpoints) placebo-corrected mean absolute reduction in LDL-C at Day 510 (62.6
vs
54.0 mg/dL,
P
<0.05) and time-adjusted reduction from Days 90 to 540 (59.0
vs
51.5 mg/dL,
P
<0.05) with inclisiran were greater in females than males. Most AEs were similar between inclisiran
vs
placebo for both sexes except for injection-site AEs that were higher in the inclisiran arm than placebo (females 9.4%
vs
0.2%, males 2.8%
vs
0.9%; Table).

Conclusions:
The efficacy and safety profile of inclisiran was generally similar in both sexes, except for more inclisiran injection-site AEs (mainly mild) vs placebo, which were more frequent in females.
Abstract 16322: Safety and Efficacy of Transapical Transcatheter Aortic Valve Replacement in the Treatment of Pure Non-calcified Native Aortic Regurgitation
Authors: Shen Can , Peng Ying , Liu Lulu , Shi Jun , Guo Yingqiang , Rao Li
Published: November 2020

Background:
Transcatheter aortic valve replacement (TAVR) in patients with pure aortic regurgitation (AR) is still “off-label” use due to the lack of suitable transcatheter heart valve. This study aimed to evaluate the safety and efficacy of TAVR with J-Valve
TM
(JieCheng Medical Technology Co., Ltd., Suzhou, China) transcatheter heart valve for the treatment of patients with pure non-calcified native AR.

Methods:
The clinical and follow-up data of patients with pure non-calcified native AR treated by TAVR with J-Valve
TM
between April 2014 and November 2019 in the West China Hospital were summarized. Procedural results and clinical outcomes were analyzed using Valve Academic Research Consortium-2 criteria.

Results:
A total of 123 patients were enrolled with a mean age of 72.1±6.4 years. There were 28 cases with bicuspid aortic valve and 95 cases with trilobal aortic valve. The median follow-up period was 18 months. Transapical implantation with J-Valve
TM
was successful in all patients (100%). By the end of the follow up, the rate of all-cause mortality was 5.7%, among which 5 cases died during the perioperative period. Other results include stroke (1.6%), new permanent pacemaker implantation (8.9%), major bleeding (6.5%), acute kidney injury (2.4%) and aortic valve-related re-intervention (3.3%, they were given surgical aortic valve replacement for thrombosis of artificial valve (2 cases) or severe post-procedural paravalvular leakage (2 cases)). Among the 112 survival cases without re-intervention, Echocardiography revealed that none of them had moderate or severe paravalvular leakage; mild and mild-moderate paravalvular leakage occurred in 9.8% and 8.0% cases, respectively. Mean transvalvular gradient after valve implantation was 9.2±3.5 mmHg. At 6 months of follow up, left ventricular end diastolic diameter was remarkably smaller compared to that before procedure (53.5±8.2 mm vs 64.3±8.9 mm, P<0.001) and left ventricular ejection fraction was significantly increased (56.3±11.8 % vs 54.2±12.4 %, P=0.031).

Conclusions:
TAVR with J-Valve
TM
transcatheter heart valve system for treatment of patients with pure non-calcified native AR is safe and effective which may be a reasonable option in the future treatment.
Abstract 16331: Prevalence and Outcomes of Arrhythmia in Tumor Lysis Syndrome: A National Perspective
Authors: Desai Rupak , Jain Akhil , Singh Sandeep , Faisaluddin Mohammed , Malik Faizan Ahmad , Desai Virmitra , Shah Vraj , abu hassan falah , Bambhroliya Zarna , Bhuva Rushik
Published: November 2020

Introduction:
Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Epidemiology and mortality outcomes of arrhythmia in TLS are scarcely studied in the literature.

Methods:
We used the National Inpatient Sample (NIS) to study the prevalence and outcome of arrhythmia in patients hospitalized with TLS (ICD-9 code 277.88) from 2009-2014. Multivariable regression was performed to analyze TLS-related mortality.

Results:
A total of 9034 cases of arrhythmia among 37,861 TLS patients were identified. The trends in the prevalence of arrhythmia were stable with rates ranging from 19.8% to 25.8%, with the highest frequency recorded in 2014 (25.8%)
(Fig. 1A).
Atrial fibrillation (13.6%) was the most common arrhythmia followed by ventricular tachycardia in 2.6% of the patients
(Fig. 1B).
Sixty-seven percent of arrhythmias were among white old (>65) males. Arrhythmic cohort showed a higher frequency of comorbidities like fluid-electrolyte disturbances, congestive heart failure, renal failure, pulmonary circulatory disorders, deficiency anemias, etc. The most common malignancies were leukemia and lymphoma. Overall in-hospital mortality (32% vs 21.3%), the median length of stay (11 vs. 9 days) and hospital charges were higher among arrhythmic TLS patients.

Conclusions:
In this population-based analysis, arrhythmia in TLS was associated with higher odds of mortality and increased resource utilization. Strategies to improve the management of TLS to prevent arrhythmia is of utmost importance.
Abstract 16333: Racial Differences in Pressure-volume Relationships in Val122Ile Associated Cardiac Amyloidosis
Authors: Batra Jaya , olivotto iacopo , Maurer Mathew S
Published: November 2020

Background:
Transthyretin cardiac amyloidosis (ATTR-CA) is the leading cause of restrictive cardiomyopathy in older adults. The valine-to-isoleucine substitution (Val122Ile) is the most common inherited variant in the U.S., primarily affecting patients of Afro-Caribbean descent. This variant has also been identified in white individuals in Northern Italy who present with a similar disease phenotype. It is unknown whether there are between-race differences in cardiac chamber function at diagnosis of Val122Ile associated ATTR-CA.

Methods:
In this retrospective study of 70 patients from two amyloid centers with Val122Ile associated ATTR-CA diagnosed over two decades, clinical and echocardiographic features at diagnosis were compared between races. Cardiac chamber performance was compared using noninvasive, single beat pressure-volume analysis.

Results:
Average age at diagnosis was 72 years. Compared to white patients (n=17), black individuals (n=53) had lower systolic blood pressure (110 vs. 131 mmHg , p<0.001), reduced pulse pressure (41 vs. 58 mmHg, p<0.001), and impaired renal function (eGFR 46 vs. 67 mL/min/1.73m
2
, p<0.001) at the time of diagnosis. End-systolic pressure-volume relationship (2.3 vs. 1.9 mmHg/mL, p = 0.88), and arterial elastance (3.0 vs. 3.0 mmHg/mL, p = 1.0) were similar between groups (Panel A). Black patients had an end-diastolic pressure-volume relationship shifted upward and leftward relative to white patients, indicating reduced left ventricular capacity. Accordingly, pressure-volume area at a left ventricular end-diastolic pressure of 30 mmHg was lower in black compared to white individuals (8,415 vs. 11,538 mmHg*mL, p = 0.012, Panel B).

Conclusion:
Despite presenting at a similar age to white patients, black individuals with Val122Ile associated ATTR-CA have a greater degree of cardiac remodeling which drives reduced overall chamber function. These findings suggest a more aggressive disease phenotype.
Abstract 16335: Metabolic Reprogramming From Glycolysis to Amino Acid Utilization in Cardiac Hif1 Alpha Deficient Mice
Authors: Menendez-Montes Ivan , Escobar Beatriz , Gómez Manuel J , Albendea-Gomez Teresa , Palacios Beatriz , Bonzon Elena , Alonso Ana V , Ferrarini Alessia , Jimenez-Borreguero Luis J , Vazquez Jesus , Martin Puig Silvia
Published: November 2020

Introduction:
Hypoxia is an important environmental cue implicated in several physiopathological processes, including cardiac development. Several gain of function models described before indicate that HIF1 signaling needs to be tightly regulated to ensure proper heart formation. However, there is lack of consensus about the functional outcomes of cardiac HIF1 elimination. We have previously reported that HIF1alpha expression is spatiotemporally regulated along cardiogenesis, establishing metabolic territories in the embryonic myocardium and controlling a switch from glycolysis to fatty acid oxidation (FAO) essential for chamber formation and cardiomyocyte maturation.

Objectives and Hypothesis:
We aim to assess the consequences of cardiac deletion of HIF1alpha during heart development and identify the adaptations to HIF1 signaling loss. Based on the tight regulation of HIF1alpha expression during cardiogenesis, we anticipated significant alterations of cardiac metabolism as well as functional and structural defects in HIF1alpha mutants.

Methods and Results:
A new conditional Hif1alpha knock out was generated in NKX2.5 cardiac progenitors. By means of histology, electron microscopy and high-throughput genomics, proteomics and metabolomics, we found that deletion of Hif1alpha leads to impaired embryonic glycolysis without influencing cardiomyocyte size or proliferation and results in increased mitochondrial number, transient activation of amino acid response and upregulation of HIF2alpha and ATF4. HIF1alpha mutants display normal FAO metabolic profile and do not show cardiac dysfunction in the adulthood.

Conclusions:
We demonstrated that HIF1 signaling is dispensable for heart development and uncovered the metabolic flexibility of the mammalian embryonic myocardium, able to utilize alternative fuels to carbohydrates in contrast to other vertebrates like zebrafish. This data highlights the importance of HIF in cardiac metabolic programing and could explain the distinct proliferative and regenerative capacity of cardiomyocytes from different species in response to cardiac injury.
Abstract 16337: A Risk Score That Predicts Recurrence of Neurally Mediated Syncope Using Electrocardiographic and Vectorcardiographic Parameters
Authors: Tentea Calina-Patricia , Chiorescu Roxana , Crisan Sorin , Pop Sorin , Ruskin Jeremy N , Blendea Dan
Published: November 2020

Introduction:
We have previously demonstrated that isolated very low QRS voltage (VLV defined as ≤0.3mV) in the frontal leads on the electrocardiogram (ECG; Figure A), as well as flat QRS loops in the frontal plane on ECG-derived vectorcardiograms (VCG; Figure B) predict recurrence of neurally mediated syncope (NMS). This phenomenon is possibly related to a specific ventricular geometry and activation pattern.

Hypothesis:
The aim of this study was to attempt to incorporate these novel ECG and VCG risk factors for recurrence of syncope into a prognostic risk score.

Methods:
We included 215 patients (age 48±20years), with NMS and a median of 3 syncopal episodes. The patients were followed for a median of 10 months (IQR 4-20). To weigh the relative importance of the prognostic risk factors identified in multivariate Cox regression analysis we attributed a score of 1 point for HR 1.5-1.99, 2 points for HR 2.0-2.49, and 3 points for HR ≥ 2.5. The total risk score, was divided into three categories: low risk (0-2), intermediate risk (3-5) and high risk (≥6).

Results:
The multivariate analysis identified history of ≥ 2 syncopal events (HR 3.85, 95%CI 1.62-9.14), left ventricular end-diastolic diameter of < 39mm by echocardiography (HR 1.94, 95%CI 1.00-3.82), isolated VLV QRS in frontal leads (HR 2.60, 95%CI 1.37-4.86) and flat QRS VCG loops in frontal plane (HR 2.23, 95%CI 1.24-3.99) as independent predictors for NMS recurrence (all P < 0.05). The actuarial total syncope recurrence rate at 1 year was 54.6% (95%CI 38.2-72.6) in the high-risk score category, 25.3% (95%CI 16.8-37.1) in the intermediate risk category, and 6.2% (95%CI 2.2-16.2) in the low-risk category (log rank test P<0.0001; Figure C). The ROC curve showed an AUC of 0.77 for the predictive value of the total risk score.

Conclusions:
The risk of recurrence of NMS could be stratified using a risk score that incorporates novel ECG and VCG parameters in addition to more established clinical and echocardiographic variables.
Abstract 16339: Mitochondrial Function in Animal and Novel Human Disease Models of Tachycardiomyopathy
Authors: Paulus Michael G , Renner Kathrin , Pabel Steffen , Pietrzyk Gabriela , Luchner Andreas , Maier Lars S , Birner Christoph M , Streckfuß-Bömeke Katrin , Sossalla Samuel T , Dietl Alexander
Published: November 2020

Introduction:
Clinical significance of tachycardiomyopathy (TCM) increased with trials on catheter ablation therapy. Myocardial biopsies from patients show disturbed mitochondrial architecture.

Hypothesis:
TCM involves mitochondrial dysfunction.

Methods:
First, TCM was investigated in an animal model: pacemaker implantation in 7 rabbits was followed by tachypacing for 30 days (TCM), 7 animals served as sham-operated controls (SHAM). Second, results of the animal study were evaluated for their translational perspective for human disease using a novel model of induced pluripotent stem cell-derived cardiomyocytes (iPS-CM), derived from 4 healthy donors. IPS-CM were paced with 120 bpm (TACH) or 60 bpm (CTRL) for 7 days in vitro. Targeted transcriptomics, high-resolution respirometry and flow cytometry (MitoSOX Red) were performed. To account for variations between cell differentiations, experiments on iPS-CM were carried out in a paired design.

Results:
TCM showed LV dilatation and dysfunction (ΔLVEDD +5.3±0.2mm; ΔFS -19±8%; TCM-SHAM; p<0.001). Histological findings resembled human disease entailing cardiomyocyte hypertrophy (CSA 519±32μm
2
vs. 413±21μm
2
, p<0.01) without fibrosis (hydroxyproline content, p=0.52). Mitochondrial transcriptome of TCM was characterized by downregulation of 10 antioxidative enzymes (e.g. GPX3, fold change (FC) 0.4; TCM/SHAM; p<0.05) as well as mitochondrial carriers, including ADP/ATP- and NADH-shuttling (SLC25A4, FC 0.7; SLC25A12, FC 0.8; p<0.01). As transcriptomics implied impaired substrate import, respirometry was performed in whole tissue. In support of our findings on the transcriptome level, mitochondrial oxidative phosphorylation capacity decreased in TCM (133±13 vs. 170±16 pmol·O
2
·s
-1
·mg
-1
·tissue, p<0.05). Similarly, oxidative phosphorylation was reduced in iPS-CM (995±738 vs. 1838±901 pmolO
2
·s
-1
·IU
-1
citrate synthase activity, TACH vs. CTRL, p<0.01). Concurrently, tachypacing increased mitochondrial superoxide emission in iPS-CM (MFI 491±206 vs. 301±119, p<0.05).

Conclusions:
Persistent tachycardia alters two mitochondrial key functions in an animal and a novel human ex vivo model: oxidative phosphorylation capacity is reduced, while superoxide emission increases.