bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10052: Leadless Pacemaker and Deep Brain Stimulator: Proximity Without Interference
Authors: Srivastava Shaurya , Jamal Shakeel , Banga Sandeep , Thakur Ranjan K
Published: June 2023

Introduction:
Deep Brain Stimulator (DBS) treatment is a known form of treatment for advanced Parkinson’s disease refractory to medical therapy. With the current aging population, instances where cardiac implantable electronic devices are becoming more frequent. Due to risk of complications from implantation of both devices, literature has recommended keeping a minimum distance of 20cm (or 6in) between the two generators. In this case we have demonstrated a successful leadless pacemaker placement at 37mm apart without any complications.

Case Report:
75 year old female with past medical history of essential tremor status post left VIM and VOA/VOP deep brain stimulator placement in 2019 presented to the emergency department with chief complaint of fall secondary to weakness. Electrocardiogram demonstrated Afib with RVR. Heparin was started for anticoagulation as the patient's CHADSVASC score was noted to be 5. Rate control was unsuccessful despite attempts with Metoprolol, digoxin loading, and max use of intravenous Cardizem. Cardioversion was not an option as the patient would need to commit to 4 weeks of uninterrupted therapeutic anticoagulation and be unable to undergo lung biopsy for new found lung mass. Extensive discussion was held with the patient and it was determined to proceed with AV nodal ablation with leadless pacemaker placement. Patient underwent successful placement of the Medtronic MC1VR01 US leadless pacemaker 37mm apart from the prior DBS device. Patient’s heart rate after the procedure remained stable at the lower rate of 80bpm with follow up device check in clinic showing no complications or interference among devices.
Abstract 10065: Higher Cholesterol Absorption Marker at Baseline Predicts Less Cardiovascular Events in Elderly Patients With Hypercholesterolemia Treatment: Kyushu Elderly Ezetimibe Phytosterol (KEEP) Study
Authors: Ouchi Yasuyoshi , Sasaki Jun , Oikawa Shinichi , Nakagawa Kiyotaka , Sato Masao , Koba Shinji , SAIKAWA Tetsunori , Kuwabara Masanari , Arai Hidenori
Published: June 2023

Introduction:
Serum cholesterol levels depend on both cholesterol synthesis in the liver and absorption in the intestine. The higher absorption of cholesterol is reported to be related to a higher incidence of cardiovascular events (CVEs).

Hypothesis:
When treated with a cholesterol absorption inhibitor, higher cholesterol absorption marker could be associated with less CVEs.

Methods:
The participants in the Kyushu Elderly Ezetimibe Phytosterol (KEEP) study were the intension-to-treat (ITT) population of the EWTOPIA75 study which has proved the beneficial effect of ezetimibe on the prevention of CVEs in the elderly older than 75 years old (Ouchi Y, et al: Circulation 140:992-1003, 2019). A total of 1,131 participants were randomly assigned to a group receiving diet therapy only (diet group) and a group receiving ezetimibe (10 mg/day) in addition to diet therapy (ezetimibe group), and were followed up for 4 years. Blood sampling was performed at baseline and at 24 weeks of follow-up to measure serum lipids and related compounds including cholesterol absorption and synthesis markers. Serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were also measured. The data of 1,061 participants (501 in the ezetimibe group and 560 in the diet group) were analyzed.

Results:
The mean age of participants analyzed was 80.5+/-4.8, and the female to male ratio was 3.2. The number of CVEs was 64. Both higher levels of campesterol (cholesterol absorption marker) and campesterol/lathosterol (cholesterol synthesis marker) ratio at baseline were significantly associated with lower risk of CVEs by ezetimibe (p=0.01 and p=0.04, respectively). No interaction of either lathosterol or campesterol with ezetimibe treatment on CVEs was found. NT-pro BNP was significantly associated with the risk of CVEs (p=0.004), but not hs-CRP.

Conclusions:
The KEEP Study has revealed that CVEs were significantly reduced in hypercholesterolemic participants with higher levels of campesterol, suggesting a rationale to treat patients with higher level of cholesterol absorption marker by ezetimibe which has been proved to be effective for the prevention of CVEs.
Abstract 10067: Association of Race and Education With Postpartum Cardiology and Primary Care Follow-Up Among Women With Preeclampsia
Authors: Countouris Malamo E , Shapero Kayle , Hauspurg Alisse , Swabe Gretchen , Magnani Jared W
Published: June 2023

Introduction:
Preeclampsia is associated with cardiovascular disease (CVD), and follow-up in women for CVD prevention is essential. We examined racial differences in follow-up with primary or cardiology care and assessed if social factors modified that association.

Methods:
We conducted our analysis in an administrative database (Optum’s de-identified Clinformatics® Data Mart) and identified women with preeclampsia diagnosed from 9/2014-9/2019. Odds of a follow-up visit with a primary care provider or cardiologist within 6 months after delivery were compared among Black versus White women using multivariable logistic regression models adjusting for age, comorbidities (by Elixhauser score), income, education, insurance type, and number of adults per household. We examined the effect modification of education and income on follow-up by race. A Cox proportional hazard model was used to compare time to follow-up.

Results:
Of 22,887 women with a diagnosis of preeclampsia (age 31.7±5.6 years), 2,736 (12.0%) were identified as Black race and 3440 (15.0%) Hispanic. Education, income, and comorbidities differed by race and ethnicity. Black women had lower odds of follow-up with a primary care provider or cardiologist within 6 months after delivery: adjusted odds ratio (aOR) 0.85 [95% confidence interval (CI) 0.78-0.92] compared with White women and were 13% less likely to have follow-up in adjusted time to event models. Hispanic women also had lower odds of follow-up: aOR 0.84 [95% CI 0.78-0.91] and were 12% less likely to have follow-up compared with white women. There was an effect modification of education by race on follow-up (p for interaction=0.001), but not income (p for interaction=0.14).

Conclusions:
Black and Hispanic women have decreased odds of follow-up with a primary care provider or cardiologist than White women in the 6 months postpartum, a disparity that may be modified by socioeconomic factors. Improving follow-up care for Black women, particularly those with less than a college-level education, may enhance CVD prevention.
Abstract 10070: Valve-in-Valve Transcatheter Mitral Valve Replacement versus Redo Surgical Mitral Valve Replacement-Sytemetaic Review and Meta-Analysis
Authors: Zahid Salman , Inayat Arslan , Hamayel Abdallah , Salman Fnu , Jain Deeptanshu , Humayun Omama , WARRAICH SAMI , Goel Sachin S.
Published: June 2023

Introduction:
Data on comparative outcomes between valve in valve transcatheter mitral valve replacement (ViV-TMVR) versus redo-surgical mitral valve replacement (SMVR) for degenerated bioprosthetic valves remain limited.
Hypothesis:
ViV TMVR is associated with lower in-hospital mortality and complication rates compared with redo SMVR.

Methods:
The MEDLINE (PubMed, Ovid) and Cochrane databases were queried with various combinations of medical subject headings (MeSH) to identify relevant articles. Eight studies evaluating comparative outcomes (ViV TMVR vs Redo SMVR) for patients with degenerated bioprosthetic valves were included in the analysis.

Results:
A total of 5,161 patients with degenerated prosthetic mitral valves underwent ViV TMVR (n = 1163) and redo SMVR (n = 3998) were included in the study. The mean age of patients was 76 versus 66 years for ViV TMVR versus the redo SMVR group, respectively (p<0.01). In terms of comorbidities, female gender (55% vs 53.4%), serum creatinine (1.52 vs 1.3), dialysis (6.4% vs 6.6% ), LVEF (55.56+/-9.5 vs 57.35+/-8.7), diabetes (20.2% vs 19.5%), hypertension (73.5% vs 63.4%), atrial fibrillation (64.5% vs 69% ), and mitral regurgitation (82.4% vs 80.5%) were similar between the ViV TMVR and redo SMVR groups respectively. Using a pooled analysis, in-hospital mortality, and major bleeding were significantly lower for patients undergoing ViV TMVR compared with redo SMVR. No significant difference was observed in the incidence of stroke. The length of stay was significantly lower in the ViV TMVR group compared with the redo SMVR group.

Conclusions:
ViV TMVR is associated with lower in-hospital mortality, complications, and length of hospital stay compared with redo SMVR for degenerated bioprosthetic valves.
Abstract 10098: Assessment of a Rate Pressure Product Target During Stress Echocardiograms in Patients With Advanced Cirrhosis
Authors: Arman Huseyin E , Ali Saad A , Elsner Nathaniel , Ofner Susan , Li Xiaochun , Zenisek Joseph , Frick Kyle
Published: June 2023

Introduction:
Dobutamine and exercise stress echo are routinely performed on patients with advanced cirrhosis though have low sensitivity in this patient population, even when target heart rate is achieved. This is in part due to their unique cardiovascular physiology which is frequently marked by reduced peripheral vascular resistance with low blood pressure, impaired chronotropic response to stress, hyperdynamic left ventricular systolic function and elevated cardiac output. In the general population, achieving a rate pressure product (RPP), defined as peak systolic blood pressure multiplied by peak heart rate, > 25,000 is typically considered a high level of stress and is an adequate workload to detect ischemia, however this has not been validated in patients with advanced cirrhosis. We aimed to assess the impact of achieving a RPP > 25,000 on the ability of stress echo to detect obstructive coronary artery disease (CAD) in patients with advanced cirrhosis.

Methods:
We performed a case-control study on patients with advanced cirrhosis where 88 had and 97 did not have CAD based on invasive coronary angiography. A total of 159 patients (85.9%, 77 with CAD and 82 without) had dobutamine and 26 (14.1%, 11 with CAD and 15 without) had exercise as their stress modality. Continuous variables were compared by means of Wilcoxon Rank Sum test. Categorical variables were expressed as numbers and percentages and compared by means of chi-square and Fisher exact tests.

Results:
The average maximum RPP was 19,999 ± 4,969.4 with 32 patients (17.3%) achieving a RPP > 25,000 (14 with and 18 without CAD, P = 0.63). The average percent of maximum predicted HR (MPHR) achieved was 86.7 ± 9.2% with 136 patients (73.5%) achieving > 85% of MPHR. Achieving a maximum RPP > 25,000 (OR 0.83, 95% CI 0.39 - 1.79, P = 0.63) or a MPHR > 85% (OR 1.04, 95% CI 0.54 - 1.99, P = 0.92) did not improve the ability of stress echo to detect obstructive CAD.

Conclusions:
Achieving a maximum RPP > 25,000 did not improve the ability of stress echo to detect obstructive CAD in patients with advanced cirrhosis.
Abstract 101: Distinctive Individual Effects of LPC(18:2) and LPC(22:6) on Survival and Neurological Outcomes After Cardiac Arrest: Combination As A Future Therapy
Authors: Choudhary Rishabh C , Yin Tai , Espin Blanca B , Shoaib Muhammad , Nishikimi Mitsuaki , Yagi Tsukasa , Becker Lance B , Kim Junhwan
Published: June 2023

Introduction:
Decreased plasma Lysophosphatidylcholine (LPC) was found to be associated with survival after cardiac arrest (CA) in humans and rats. Supplementing LPC species containing docosahexaenoic acid, LPC(22:6), improved rat brain function and survival after CA. Thus, LPC deficiency may be a major cause of CA pathology and LPC supplementation may be a novel therapeutic approach to CA. However, the therapeutic effects of individual LPC species are not fully understood, particularly a species containing linoleic acid, LPC(18:2). While 22:6 is an omega-3 fatty acid and highly abundant in the brain, 18:2 is omega-6 and minimally present in the brain. Therefore, we hypothesized that the protective role of LPC(18:2) may be different from LPC(22:6). Furthermore, LPC(18:2) may provide additive protection when administered together with LPC(22:6).

Objective:
To investigate the protective role of supplementing LPC(18:2) compared to LPC(22:6) after CA.

Methods and Results:
We first compared the relationship between plasma LPC(18:2) levels and outcomes of CA patients as compared to LPC(22:6). LPC(22:6) was found to be associated with both survival and neurological outcomes, whereas the levels of LPC(18:2) were associated with survival only. We then tested whether supplementing LPC(18:2) can improve survival and neurological function in rats undergoing 10 minutes of asphyxial CA. Supplementing LPC(18:2) post-resuscitation significantly improved survival as did LPC(22:6) in rats. Although LPC(18:2) supplementation improved in some individual neurofunctional tasks, the overall neurological function of survived rats was not improved. Particularly, while 3 of 7 survived rats treated with LPC(22:6) were able to walk across a ledge, none of 10 survived rats treated with LPC(18:2) were able to cross the ledge.

Conclusion:
Significantly improved survival without significantly improved brain function in rats and poor correlation with neurological outcomes from humans suggest that LPC(18:2) may protect organs other than the brain. The results further indicate that different LPC species have different mechanisms of improving outcomes, demonstrating the potential of utilizing different combinations of LPC as improved therapeutic treatments in CA.
Abstract 10111: Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial
Authors: Huo Yong , Li Yong , Zhang Ping , Deng Huan , Li Haoyu , An Pei , Xue Fengtai , Yu Zhongxun , Ma Qingyang , Qi Litong , Chen Beijian , Lian Qiufang , Wang Shuqing , Lu Di , QIAN LEI ,   CREDIT-1 Investigators
Published: June 2023

Introduction:
Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285).

Methods:
Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C <1.8 mmol/L and LDL-C <1.4 mmol/L.

Results:
A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L and LDL-C <1.4 mmol/L compared with corresponding placebo groups (
Table
). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia.

Conclusions:
Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.
Abstract 10113: Validation of a Deep-Learning-Based Retinal Biomarker in the Prediction of Cardiovascular Disease: Data From UK Biobank
Authors: Tseng Rachel M , Rim Tyler Hyungtaek , Shantsila Eduard , Park Sung Ha , Kim Sung Soo , Lee Chan Joo , Tham Yih Chung , Thakur Sahil , Yi Joseph , Nusinovici Simon , Peng Qingsheng , Yu Marco , Lee Geunyoung , Bakhai Ameet , Leeson Paul , Lip Gregory , Wong Tien Y , Cheng Ching-Yu
Published: June 2023

Introduction:
Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, with a benchmark of 10% for 10-year CVD risk determining clinical intervention. Yet, effects on clinical practice are limited and the barriers call for a simple, non-invasive risk stratification tool. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aimed to further validate our biomarker, Reti-CVD,

1)

to detect risk group of ≥10% in 10-year CVD risk and

2

)

enhance risk assessment in individuals with QRISK3 of 7.5%-10% (termed as borderline-QRISK3 group) using the UK Biobank.

Methods:
RetiCVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of RetiCVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding RetiCVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups.

Results:
Among 45,233 participants with no history of CVD, 6.7% had CVD events during the 11-year follow-up. RetiCVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.34 (95% confidence interval [CI], 1.26-1.42) with a 14.7% (95% CI, 13.6-15.9%) 10-year CVD risk in RetiCVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in RetiCVD-high-risk group (12.8% in non-statin cohort [n=16240], 11.5% in stage 1 hypertension cohort [n=5102], and 14.9% in middle-aged cohort [n=11,474]). C statistics increased by 0.013 (0.010-0.017) in non-statin cohort, 0.017 (0.010-0.024) in stage 1 hypertension cohort, and 0.022 (0.017-0.027) in middle-aged cohort for CVD event prediction after adding RetiCVD to QRISK3.

Conclusion:
RetiCVD has the potential to identify individuals with ≥10% 10-year CVD risk who are likely to benefit from earlier, upstream preventative CVD interventions. For borderline-QRISK3 individuals, RetiCVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in early vulnerable adult groups.
Abstract 10124: Characteristics of the Right Ventricle in Left Ventricular Noncompaction With Reduced Ejection Fraction
Authors: Gregor Zsofia , Kiss Anna Reka , Grebur Kinga , Dohy Zsofia , Kovacs Attila , Merkely Bela , Vago Hajnalka , Szucs Andrea
Published: June 2023

Introduction:
Reports of left ventricular noncompaction (LVNC) rarely include descriptions of the right ventricle (RV).

Hypothesis:
This study aimed to describe the characteristics of the RV in LVNC patients with reduced LV function (LVNC-R) compared with patients with dilated cardiomyopathy (DCM) and subjects with LVNC with normal left ventricular ejection fraction (LV-EF) (LVNC-N).

Methods:
Forty-four LVNC-R patients, 44 LVNC-N participants, and 31 DCM patients were included in this retrospective study (LV-EF: LVNC-R: 33.4±10.2%; LVNC-N: 65.0±5.9%; DCM: 34.6±7.9%). Each group was further divided into two subgroups by the amount of RV trabeculation.

Results:
There was no difference in the RV-EF between the groups, and the RV trabecular mass correlated positively with the RV volume and negatively with the RV-EF in all the groups. All the measured parameters were comparable between the groups with decreased LV function. Subgroups with RV hypertrabeculation showed significantly higher RV volumes and lower RV-EF in the decreased-LV-function groups than patients with normal RV trabeculation. LV trabeculation correlated with RV volumes in both noncompacted groups, while the correlation with RV trabeculation was observed only in the LVNC-N group (r=0.469, p=0.001). Both decreased-LV-function groups had worse RV strain values than the LVNC-N group; however, RV strain values correlated with RV trabeculation predominantly in the LVNC-R group.

Conclusions:
Correlations between LV trabeculation and RV parameters and the presence and characteristics of RV hypertrabeculation raise the possibility of RV involvement in noncompaction; moreover, RV strain values might be helpful in the detection of early subclinical changes of the RV.
Abstract 10126: Impact of Albuminuria on Prognosis After Transcatheter Aortic Valve Replacement for Aortic Stenosis
Authors: Tobe Akihiro , Tanaka Akihito , Tokuda Yoshiyuki , Shirai Yoshinori , Miyazaki Tatsuya , Yuhara Satoshi , Akita Sho , Furusawa Kenji , Ishii Hideki , Murohara Toyoaki
Published: June 2023

Introduction:
Albuminuria is a well-known risk factor of cardiovascular events. However, the impact of albuminuria on the prognosis in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) has not been studied.

Methods:
This is a single-center retrospective observational study. Consecutive patients who underwent TAVI for severe AS and whose preoperative urinary data were available were included. Finally, 228 patients were investigated. Patients were divided into two groups according to the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR<30 mg/g). Total protein to creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was a composite endpoint of all-cause death and readmission due to heart failure.

Results:
There were 117 patients with a high ACR and 111 patients with a low ACR. At baseline, patients with a high ACR had significantly lower eGFR than those with a low ACR. During the median follow-up period of 467 days, the patients with a high ACR had higher incidence of a primary endpoint than those with a low ACR (p<0.001). The individual incidence of all-cause death, cardiac death and heart failure readmission were also significantly higher in patients with a high ACR than those with a low ACR. Patients with PCR≥150mg/g or positive dipstick proteinuria were at a higher risk of primary endpoint as well (p<0.001 and p=0.008, respectively), however, there was no significant difference between the patients with eGFR<60 and ≥60 mL/min/1.73m
2
(Figure). Multivariate Cox proportional hazards analysis showed a high ACR was independently associated with a primary endpoint (HR, 4.98; 95% CI, 1.84-13.49; p=0.002).

Conclusions:
Preoperative albuminuria (ACR≥ 30 mg/g) is an independent predictor of cardiac events in the patients with severe AS undergoing TAVI. PCR≥150 mg/g and positive dipstick albuminuria are also useful for risk prediction.
Abstract 10134: Role of Cardiac Sympathetic Nerves in Mediating the Central Nervous System Cardioprotective Effects of Leptin After Ischemia/Reperfusion Injury
Authors: Omoto Ana C , Docarmo Jussara M , Nelson Bejamin , Aitken Nikaela , Dai Xuemei , Moak Sydney , Wang Zhen , Mouton Alan J , Li Xuan , Hall John E , Da Silva Alexandre A
Published: June 2023

We previously demonstrated that central nervous system (CNS) administration of leptin improves left ventricular (LV) function after myocardial infarction through mechanisms that are poorly understood. Increased cardiac sympathetic activity is an important compensatory mechanism to maintain cardiac output after ischemic injury, and previous studies showed that centrally-administered leptin increases sympathetic outflow to various tissues. In the present study, we tested the hypothesis that leptin’s CNS-mediated cardioprotective effects are mediated via cardiac sympathetic nerves. Male and female Wistar rats (~8 weeks of age) were submitted to cervical ganglia denervation (CGx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO) and an exercise performance test (Vmax), myocardial ischemia/reperfusion (I/R) was induced by temporary (60 min) ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused chronically for 28 days starting 20 min after reperfusion using osmotic pumps implanted subcutaneously in the scapular region and connected to the ICV cannula. Cardiac function was assessed weekly by ECHO. At the end of week 4, a final Vmax was performed and +dP/dt
max
was accessed by LV catheterization using a Millar catheter. Despite ~70% reduction in cardiac tyrosine hydroxylase positive fibers compared to sham, CGx did not prevent leptin’s CNS-mediated cardioprotective effects as indicated by improved ejection fraction (55±1 vs. 29±3 %), global longitudinal strain (-19±2 vs. -3±2 %), +dP/dt
max
(10214±614 vs. 7174±716 mmHg/s) and exercise performance (1.3±14 vs. -46.3±14 Δ% compared to baseline before I/R) when compared with CGx vehicle-treated animals. CGx also did not prevent the effect of ICV leptin to reduce septal collagen deposition and heart weight/tibia length post-I/R. These results suggests that leptin, via its CNS actions, improves cardiac function and remodeling after I/R injury independent of cardiac sympathetic innervation.
Abstract 10176: Rate Control versus Catheter Ablation for Heart Failure Patients With Atrial Fibrillation: A Meta-Analytic Comparison
Authors: Alam Mustafa , Baqal Omar Javed , Jhamnani Sunny
Published: June 2023

Introduction:
Atrial fibrillation (AF) remains a significant cause of morbidity and mortality in the United States. Optimal management of AF in heart failure (HF) patients remains a controversy. Recent studies have demonstrated favorable outcomes of catheter ablation versus medical therapy. The purpose of this meta-analysis is to investigate whether catheter ablation achieves better outcomes as compared to rate control.

Methods:
A systematic search of MEDLINE was conducted using PRISMA guidelines with the search terms “rate control”, “atrial fibrillation”, and “ablation.” Studies were included if they compared a catheter ablation strategy versus rate control medical therapy in HF patients. Multiple endpoints were extracted from the articles including LVEF, 6MWD, change in BNP, and Quality of Life (QoL) outcomes using the Cochrane manual. Revman 5.4 was used to aggregate the outcomes and compute statistics using a random effects model to create forest plots.

Results:
A total of 7 studies with 1065 patients were included in this analysis. LVEF increased by 5.69% [4.80, 6.58] p<0.00001, 6MWD increased by 24.82m [2.69, 46.94] p=0.03, BNP decreased -102.54 [-174.68, -30.40] p=0.005, and QoL outcomes using the MLHFQ improved -8.10 [-15.73, -0.48] p=0.04.

Conclusions:
Catheter ablation improves outcomes in HF patients with atrial fibrillation as compared to a rate control only strategy. Further large-scale randomized studies are needed to quantify improvements in outcomes.
Abstract 10191: Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Blood Pressure Trajectories in Middle-Aged Adults
Authors: Khan Bilal , Scherzer Rebecca , Lewis Cora E , Shlipak Michael , IX Joachim H , GUTIERREZ Orlando M
Published: June 2023

Introduction:
Kidney tubules play a key role in regulating blood pressure (BP). Urine biomarkers of kidney tubule injury associate with incident hypertension (HTN) in older adults with multiple comorbidities. Less is known about these associations in younger adults.

Hypothesis:
Urine biomarkers of kidney tubular injury and dysfunction associate with incident HTN and greater 10-year rise in BP in middle-aged adults.

Methods:
In 1,170 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study (mean age 45±4, 40% black, 56% women) without HTN, cardiovascular disease or kidney disease at the year 20 exam (baseline for this analysis), we measured urine monocyte chemoattractant protein-1, alpha-1-microglobulin, kidney injury molecule-1, epidermal growth factor [EGF], interleukin-18, chitinase-3-like protein 1, and uromodulin. We examined associations of biomarkers with incident HTN (onset of systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg or initiation of BP meds) after baseline in interval-censored Cox models and BP trajectories in linear mixed models adjusted for established risk factors.

Results:
During a median 9.9 years of follow up (IQR 5.9-10.2), 376 incident HTN events occurred. Compared to the lowest tertile of EGF, the risk of incident HTN was lower in the two higher tertiles in the model adjusted for age, sex, race, and urine creatinine, and in the fully adjusted model (Figure). The mean increase in SBP over 10 years was 3.4 mmHg lower in Tertile 3 vs. Tertile 1 of EGF (95%CI -6.1, -0.7). There were no statistically significant associations of urine EGF with incident HTN or BP trajectories when EGF was modeled as a continuous predictor. There were no statistically significant associations of other biomarkers with incident HTN or BP trajectory.

Conclusions:
In middle aged adults without HTN, cardiovascular or kidney disease, higher urine EGF levels associated with lower risk of incident HTN and lower 10-year mean rise in BP.
Abstract 10200: Costs and Resource Utilization of People With Stable Heart Failure and Insomnia: Evidence From a Randomized Trial
Authors: Hollenbeak Christopher S , Jeong Sangchoon , O'Connell Meghan , Redeker Nancy S , Yaggi Henry
Published: June 2023

Introduction:
Nearly half of patients with chronic heart failure (HF) report insomnia symptoms. Cognitive behavioral therapy for insomnia (CBT-I) is efficacious for treating insomnia in the presence of comorbid conditions. This study estimated healthcare costs and resource utilization for people with stable chronic HF and insomnia using data from an NIH-funded clinical trial comparing CBT-I with an HF self-management

Methods:
Using data from the HeartSleep Study, we examined resource utilization one year following randomization. Resource utilization was measured as self-reported physician office visits, emergency department visits, and inpatient admissions, collected at each follow-up. Costs were estimated by applying price weights to visits, and adding self-reported out of pocket expenses and indirect costs. Univariate comparisons were made of resource utilization and costs between CBT-I and attention control groups. A generalized linear model (GLM) was used to model costs, controlling for covariates.

Results:
There were no significant differences in demographic characteristics between patients who received CBT-I (N=79) and those who received HF self-management (attention control) (N=71). During the first year following randomization, participants receiving CBT-I had 4.2 inpatient hospitalizations compared to 4.6 for the attention control group (p = 0.40). Participants receiving CBT-I also had 13.1 outpatient visits on average, while control participants had 15.4 outpatient visits. Relatively few emergency department visits were required by either CBT-I or attention-control participants. Overall, total costs were slightly higher for participants who received CBT-I ($7,813 vs. $7,538, p = 0.96). In the multivariable analysis participants who received CBT-I had $630 in higher costs, but this was not statistically different from the attention control group.

Conclusions:
Among patients with both HF and insomnia, CBT-I and HF self-management had similar resource utilization and total costs. Additional research is needed to estimate the value of CBT-I relative to other treatments for insomnia in patients with HF.
Abstract 10202: DNA-PKcs: A Novel Therapeutic Target in Pulmonary Arterial Hypertension
Authors: Yamamoto Keiko , Yokokawa Tetsuro , Lemay Sarah-Eve , Bourgeois Alice , Shimauchi Tsukasa , Shimauchi Kana , Nadeau Valerie , SALEM MABROUKA , Breuils Bonnet Sandra , potus francois , Boucherat Olivier , Provencher Steeve , Bonnet Sebastien
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular obliteration of small pulmonary arteries (PAs), notably due to excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs). Accumulating evidence indicates that PAH-PASMCs have acquired an over-efficient DNA damage response (DDR) ensuring sensing, signaling, and repair of DNA damages, accounting for their enhanced capacity to survive and proliferate under stressful conditions. DNA-dependent protein kinase (DNA-PK) is a pivotal component of the DNA repair machinery which plays an instrumental role in the overall survival and proliferation of cancer cells. Based on similarities between PAH and cancer cells, we thus hypothesized that increased expression of DNA-PK contributes to vascular remodeling in PAH.

Methods and Results:
Using Western blot (WB) and immunohistochemistry, we found that expression and activity of DNA-PK were increased in PAH-PASMCs (n=6) compared to controls (n=6, p<0.01). Similarly, DNA-PK was significantly up-regulated in distal PAs from PAH animal models (i.e. MCT rats and Su/Hx rats and mice, n=5/group, p<0.01). In vitro, the pharmacological inhibition of DNA-PK using AZD-7648 or Nedisertib attenuates PAH-PASMC proliferation (Ki67 and EdU labeling, MCM2, PLK1, and PNCA by WB; p<0.05) and resistance to apoptosis (AnnexinV labeling, Survivin by WB)(n=5 cell lines; p<0.05). These effects were associated with reduced expression of gH2AX. As assessed by echocardiography and right heart catheterization, treatment with AZD7648 improved pulmonary hemodynamics (RVSP, mPAP, and TPR) and right ventricular function (CO, PAT/PET, TAPSE) in Su/Hx mice with established PAH (n=10/group; all p<0.01). Accordingly, pulmonary vascular remodeling (EVG) and the proportion of PCNA-positive PASMCs were reduced in AZD7648-treated Su/Hx mice when compared to vehicle-treated Su/Hx mice (p<0.001).

Conclusions:
We showed for the first time that DNA-PK is overexpressed in human and experimental PAH and contributes to the pro-proliferative and anti-apoptotic phenotype of PAH-PASMCs.
Abstract 10210: Citalopram, but Not Fluoxetine May Improve Post-Stroke Recovery
Authors: Toubasi Ahmad A , Kalbouneh Heba M , Albustanji Farah H , Obaid Yazan Y , Al-Harasis Layla M
Published: June 2023

Introduction:
Several studies evaluated the role of Selective Serotonin Reuptake Inhibitors (SSRIs) in several aspects of stroke recovery. However, the results of these studies were inconsistent.
Hypothesis
This study was conducted to assess the hypothesis that SSRIs improve post-stroke recovery.

Methods:
In this systematic review and meta-analysis, we searched the following databases: PubMed, Cochrane, Scopus and Google Scholar. The studies were included if they were placebo-controlled trials in design and reported SSRIs effects on post-stroke depression, anxiety, disability, dependence, motor abilities and cognitive functions.

Results:
The search yielded 44 articles that included 16,164 patients and about half of the participants were treated with SSRIs. Our results showed that SSRIs had significant effect on preventing depression (Figure 1: Weighted Mean Difference (WMD)=-7.05; 95%CI: -11.78- -2.31), treating depression (Figure 1; WMD=-1.45; 95%CI: -2.77- -0.14), anxiety (Figure 1: Relative Risk (RR)=0.23; 95%CI: 0.09-0.61), dependence (Figure 1: WMD=8.86; 95%CI:1.23-16.48), motor abilities (Figure 1: WMD=-0.79; 95%CI: -1.42- -0.15) and cognitive functions (Figure 1: WMD=1.00; 95%CI: 0.12-1.89). On the other hand, no significant effect of SSRI on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (RR=1.44; 95%CI:1.13-1.83).

Conclusion:
Our study showed that SSRIs are effective in preventing and treating depression, improving anxiety, motor function, cognitive function and dependence in post-stroke patients. These benefits were only reproducible with the citalopram sub-analysis but not fluoxetine; further well-conducted placebo-controlled trials are needed to investigate the safety and efficacy of citalopram among post-stroke patients.
Abstract 10214: Invasive versus Echocardiographic Hemodynamics in the First Genetically Modified Porcine to Human Xenotransplant
Authors: Soares Cullen , Hong Susie N , Hanna Peter , Goerlich Corbin E , Hong Charles C , Dickfeld Timm , Grazioli Alison , Mohiuddin Muhammad , Griffith Bartley , Ananthram Manjula
Published: June 2023

Introduction:
Our medical center performed the first genetically modified cardiac xenotransplant in human and performed longitudinal invasive and noninvasive hemodynamic measurements throughout the recipient’s hospitalization. We hypothesized that echocardiographic derived hemodynamic assessments would correlate with invasive measurements within the cardiac xenotransplant.

Methods:
Transthoracic echocardiography (TTE) and right heart catheterizations were performed in the cardiac xenotransplant. Retrospective analysis of TTE and invasive hemodynamics were analyzed to assess correlation between various parameters. The following invasive hemodynamics were measured or calculated: right atrial pressure (RAP), pulmonary artery systolic and diastolic pressures (PASP, PADP), pulmonary vascular resistance (PVR), pulmonary artery pulsatility index (PAPi), cardiac output (CO), cardiac index (CI), right ventricular stroke work index (RVSWI) and cardiac power output (CPO). TTE measurements and calculations included: RAP based on inferior vena cava size and collapsibility, PASP calculated via tricuspid regurgitation velocity (TRV), PADP based on end diastolic pressure gradient, right ventricular outflow time-velocity integral (TVI RVOT), PVR (TRV/TVI RVOT x 10 +0.16) PAPi, CO (using left ventricular outflow tract (LVOT) velocity-time integral and LVOT area), CI (from TTE-derived CO), CPO and RVCPI {4x(TRV)
2
} x TAPSE as a surrogate of RVSWI.

Results:
Pearson correlation for RVSWI and RVCPI using invasive measurements obtained at the time of TTE was -0.095 and at time of mixed venous blood gas (mVBG) was 0.963. Mean absolute difference in time between mVBG and TTE was 4h 59 min. Pearson correlation for catheter-based continuous CO (CCO) monitoring with TTE was 0.965.

Conclusions:
In a retrospective analysis of porcine cardiac xenotransplant function, there was a strong correlation between directly measured hemodynamics with TTE, particularly when mVBG was obtained.
Abstract 10218: Differences in Treadmill Exercise Stress Testing Parameters Among Electronic Cigarette Vapers, Combustible Cigarette Smokers, and Controls: The Clues Study
Authors: Hughey Christina M , Piasecki Thomas M , Korcarz Claudia E , Hansen Kristin M , Ott Nancy R , Tattersall Matthew C , Fiore Michael C , Baker Timothy B , Stein James H
Published: June 2023

Background:
Use of electronic nicotine delivery devices is increasing but their effects on exercise function are not well-characterized. We hypothesized that treadmill stress test outcomes would differ between chronic electronic cigarette users (“vapers”), combustible cigarette users (“smokers”), and non-smoking/non-vaping controls.

Methods:
CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] <5 ppm, positive urine NicCheck I), 117 exclusive smokers (CO >5 ppm, positive urine NicCheck I), and 114 non-vaping/non-smoking controls (CO <5 ppm, negative urine NicCheck I). Participants completed a symptom-limited Balke treadmill stress test protocol, a mean (SD) of 91.3 (16.2) minutes after vaping, smoking, or resting. Outcome measures were peak achieved metabolic equivalents (METs), rate-pressure product (RPP, peak heart rate [HR]*systolic blood pressure), HR reserve (peak HR/[220-age]), and 60-second HR recovery (HRR60). Group differences were compared by general linear models with omnibus p-values adjusted for age, race, and sex and with
post-hoc
t-tests using Bonferroni-corrected p-values.

Results:
Vapers were 27.4 (10.6) years old (39% female, 86% white) and had vaped for 4.1 (2.7) years (16.3 [30.0] vape-years). Smokers were 42.8 (13.8) years old (44% female, 56% white) and had smoked for 23.0 (13.0) years (28.7 [26.5] pack-years). Controls were 30.8 (11.9) years old (50% female, 69% white). Age, race, and sex-adjusted mean (95% CIs) outcome values by group are in the Figure. Vapers performed worse than controls on all 4 exercise parameters: peak METs (p<0.001), peak RPP (p=0.020), HR reserve (p<0.001), and HRR60 (p=0.025) with intermediate values compared to smokers.

Conclusion:
Vapers consistently performed worse than controls on 4 treadmill exercise parameters that predict adverse cardiovascular disease outcomes with intermediate values compared to smokers.
Abstract 10240: Lower May Not Be Better: Systolic Blood Pressure and Risk of Major Adverse Limb Events in Patients With Symptomatic Peripheral Artery Disease After Revascularization: Insights From Voyager Pad
Authors: Buchanan Cullen E , Szarek Michael , Debus Sebastian , Patel Manesh R , Nehler Mark , Anand Sonia S , Hess Connie , Hsia Judith A , Muehlhofer Eva , Haskell Lloyd P , Berkowitz Scott D , Bauersachs Rupert , Bonaca Marc P
Published: June 2023

Introduction:
Blood pressure (BP) trials have established optimal targets for major adverse cardiovascular event (MACE) prevention; however, less intensive BP control (also called permissive hypertension) is sometimes utilized to minimize end organ damage in specific settings such as acute stroke and acute kidney injury. An analysis from ALLHAT found that systolic blood pressure (SBP) <120mmHg was associated with a 26% higher rate of major adverse limb events (MALE) in peripheral artery disease (PAD). Whether this association is present in patients with PAD after lower extremity revascularization (LER) is not well described.

Methods:
VOYAGER PAD randomized patients with symptomatic PAD after LER to rivaroxaban or placebo. The primary composite endpoint was time to first event of MACE or MALE. BP measurements were obtained at baseline, 1, 3, and every 6 months after enrollment. Associations between average SBP at 1 month after LER and incident MACE and MALE through follow up were evaluated. Splines were estimated in proportional hazard models with adjustment for treatment assignment.

Results:
SBP measurements at 1 month were available in 6,248 patients. Median (IQR) SBP in mmHg was (126, 114-139). The relationship between SBP after LER and future risk of MACE (Figure, Panel A) shows an apparent increased risk at SBP <90mmHg. The relationship of SBP and MALE appeared linear (Figure, Panel B) with a lower risk at higher SBP and greater risk with SBP below ~120mmHg. For every 5mmHg decrease in SBP there was an associated 7% increase in risk of MALE (HR 1.07, 95% CI 1.05-1.10, p <0.0001). The pattern appeared consistent regardless of index revascularization type (surgical vs endovascular).

Conclusion:
Patients with PAD are at heightened risk of MALE due to obstructive conduit artery disease. There is an inverse relationship between SBP and MALE after LER. Further investigation into optimal BP targets in patients with PAD are warranted.
Abstract 10256: Current Indications for Surgery for Severe Mitral Regurgitation Predict Higher Risk of Mortality in Women Compared to Men
Authors: Abadie Bryan , Cremer Paul C , GILLINOV A MARC , Cho Leslie
Published: June 2023

Introduction:
Studies have shown that mitral valve repair (MVr) for severe mitral regurgitation (MR) restores normal life expectancy in men, but not in women. The reasons for this difference in long term mortality are unknown. The purpose of this study was to evaluate men and women who underwent isolated mitral valve repair and compare differences in mortality for the current AHA/ACC class I indications for surgery: symptoms, ejection fraction (EF) ≤ 60%, and left ventricular internal dimension at end-systole (LVIDs) ≥ 4.0 cm.

Methods:
All patients who underwent isolated mitral valve repair for the primary indication of degenerative MR at a single institution between 1994 and 2016 were screened. Patients were excluded if they underwent a concomitant surgical intervention or did not have 1 year of follow up data.

Results:
A total of 12,880 patients underwent surgery for severe degenerative MR of which 5,267 had an isolated MVr and 1 year of follow up data. There was 3,159 men and 2,108 women in the study. Men and women had similar age and pre-operative ejection fraction, with some difference in pre-operative comorbidities (see Figure). EF was a predictor of death in both women and men, although the hazard ratio was higher in women [HR 1. 78 (CI 1.30 - 2.40, p = 0.017) vs 1.37 (CI 1.06 - 1.78, p < 0.001)]. In men, symptoms (HR 0.98 CI 0.73 - 1.31, p = 0.878) and increased LVIDs (HR 1.12 CI 0.87 - 1.62, 0.277) did not predict mortality. However, in women, the presence of symptoms did predict death (HR 1.80 CI 1.06 - 3.05, p = 0.029). An increased LVIDs trended towards death but did not quite meet statistical significance (HR 1.41 CI 0.99 - 2.00, p = 0.059) in women.

Conclusion:
The non-gender-specific thresholds for mitral valve surgery in the current guidelines may underestimate disease severity in women as they were associated with an increased risk of death compared to men. Therefore, delaying surgery until women meet these thresholds may be exposing them to undue harm.
Abstract 10258: Rivaroxaban to Improve Clinical Outcomes in Outpatients With Covid-19: A Meta-Analysis of Two Randomized Clinical Trials
Authors: Hsia Judith A , Spyropoulos Alex , Piazza Gregory , Weng Stephen , Dunne Michael , Lipardi Concetta , Barnathan Elliot S , Bonaca Marc P
Published: June 2023

Background:
Thromboprophylaxis with rivaroxaban 10 mg once daily has been shown to reduce the risk of major thrombotic events in patients with COVID-19 both in-hospital and after discharge. The potential role of thromboprophylaxis with rivaroxaban in high-risk outpatients with COVID-19 was examined in 2 randomized, controlled trials; pooled analyses of these studies will enable evaluation of consistency of findings.

Methods:
PREVENT-HD (NCT04508023) and the Bill and Melinda Gates Medical Research Institute (Gates MRI) study (NCT04504032) are both virtually conducted, pragmatic trials which randomized patients with acute COVID-19 to rivaroxaban 10 mg daily or placebo (PREVENT-HD)/placebo equivalent (Gates MRI) on top of standard care (Figure). Both studies collected clinical outcomes including all-cause hospitalization, death, thrombotic and bleeding events. A patient-level meta-analysis was prespecified prior to PREVENT-HD database lock.

Results:
The 2 trials randomized a total of 1,781 patients. PREVENT-HD closeout is ongoing with anticipated unblinding in July 2022 and submission to AHA as an LBCT. Gates MRI study results have been reported; among the 497 randomized patients, clinical events were infrequent overall, with hospitalizations in 3 (1.4%) patients receiving rivaroxaban and 7 (3.2%) in the placebo group (RR 0.43, 95% CI 0.11, 1.65; p=0.21). A planned pooled analysis will occur after PREVENT-HD database lock enabling presentation at AHA 2022 if selected.

Conclusions:
A patient-level meta-analysis of 2 randomized, controlled trials of similar design evaluating rivaroxaban 10 mg daily for pre-hospital prevention of thrombotic complications, hospitalization, and death in outpatients with COVID-19 will be conducted. We hope to present the results at the AHA Scientific Sessions.