bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13149: Mental Stress-Induced Hemodynamic Changes and Cardiovascular Outcomes
Authors: Cheung Brian , Almuwaqqat Zakaria , Kim Jeong Hwan , Hammadah Muhammad , Shah Amit J , Ko Yi-An , elon lisa , Sullivan Samaah , Shah Anish , Alkhoder Ayman , Lima Bruno B , Pearce Brad , Ward Laura , Kutner Michael , Hu Yingtian , Lewis Tene T , Garcia Ernest V , Nye Jonathon A , Sheps David , Raggi Paolo , Bremner James Douglas , Vaccarino Viola , Quyyumi Arshed A
Published: June 2023

Introduction:
Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes.

Hypothesis:
Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events.

Methods:
Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables.

Results:
In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 - 7,120). Patients with lower RPP changes (<median) during MS were more likely to have a lower resting RPP, be male, and have a history of smoking, obesity, and heart failure. Serum epinephrine levels (22.5 ± 37.3 pg/mL; p<0.001) increased after MS and correlated with RPP changes (r = 0.32; p < 0.001). During a mean follow-up of 4.6 years, there were 135 CV death and MI events (3.2/100 patient-years) and 279 events including HF hospitalizations (6.7 events/100 patient-years). After adjusting for the baseline RPP, demographics, clinical factors, and medication, patients with lower change in RPP during MS had higher primary [HR, 1.7 (95% CI, 1.1 - 2.5); p = 0.009] and secondary events [HR, 1.5 (95% CI, 1.1 - 2.0); p = 0.006].

Conclusions:
A reduced change in RPP during MS is independently associated with worse outcomes in patients with CAD. Whether hemodynamic reactivity during MS can be clinically used to identify residual risk needs further evaluation.
Abstract 13161: Longitudinal Profiling of Fasting Plasma Metabolome in Response to Weight-Loss Interventions in Patients With Morbid Obesity
Authors: Chen Mingjing , Huo Zhiguang , Peng Hao , Miao Guanhong , Wen Xiaoxiao , Anton Stephen , Hu Gang , Brock Ricky , Brantley Phillip J , Zhao Jinying
Published: June 2023

Background:
The mechanisms underlying the favorable effects of Roux-en-Y gastric bypass (RYGB) over adjustable gastric banding (BAND) or non-surgical interventions on long-term metabolic outcomes remain largely unknown. Studies to date have largely been cross-sectional in nature and confounded by weight loss.

Objective:
Identify plasma metabolites associated with differential metabolic outcomes in response to different types of weight-loss interventions, independent of weight loss.

Methods:
We studied 75 patients with obesity (25 each in RYGB, BAND, or intensive medical intervention [IMI]) in the HeadsUp Study, a longitudinal study designed to evaluate the effectiveness of different weight-loss interventions. Using untargeted metabolomics (GC-TOF-MS), we repeatedly measured 364 metabolites (153 known) in fasting plasma samples collected at baseline and 1-year after intervention. Linear regression model was used to identify baseline metabolites predictive of changes in fasting plasma glucose (FPG) and HbA1c, adjusting for age, sex, BMI, FPG, or HbA1c at baseline and weight loss. Longitudinal associations were examined with linear mixed-effect models, adjusting for same covariates plus change in BMI and weight loss. Metabolites enrichment and network analyses were performed to identify related metabolic pathways.

Results:
We identified 41 baseline metabolites (18 known) significantly predictive of changes in FPG or HbA1c when comparing RYGB vs. IMI. Longitudinal changes in 37 metabolites (22 known) and 76 metabolites (32 known) were significantly associated with changes in FPG or HbA1c when comparing RYGB vs. IMI, and RYGB vs. BAND, respectively. The identified metabolites are enriched in pathways involved in aminoacyl-tRNA and branched chain amino acids (BCAAs) biosynthesis.

Conclusion:
Baseline plasma metabolites predict differential metabolic outcomes induced by different types of weight-loss interventions, with the effects being independent of weight loss. Our findings suggest that RYGB may exert its favorable metabolic effects via rewiring metabolism, and help identify patients who may obtain the greatest benefits from bariatric surgery.
Abstract 13162: Temporal Trends in Secondary Pulmonary Hypertension and Subsequent Mortality in Hospitalized Geriatric Patients With Prior Revascularized Myocardial Infarction (2016-2019)
Authors: Sanku Koushik , Katukuri Nishanth , Pingili Adhvithi , TAJDIN BORZOO , Zahdeh Tamer , Cherukuri Akhila S , JALILI HAMIDREZA , Bahadoran Pooriya , Srikanth Sashwath , Desai Rupak
Published: June 2023

Background:
There is limited data on the burden and impact of Pulmonary hypertension (PHTN) in geriatric patients with prior revascularized MI. This study aims to explore the burden, trends, and impact of secondary PHTN on the survival of elderly patients with established CVD risk.

Methods:
We used the National Inpatient Sample (2016-2019) to identify geriatric (≥65 years) hospitalizations with prior revascularized MI (PCI or CABG) by using ICD-10 codes and divided them into two groups: with secondary PHTN and without secondary PHTN (GPRMI-PHTN+ VS. GPRMI-PHTN-). We then compared the two groups' morbidity, mortality, and associated outcomes.

Results:
Of 2265900 GPRMI patients that were included in the study, 169942 (7.5%) had secondary PHTN (median 76 [70-82]). The PHTN cohort often had females (42.5% vs 33.7%) and blacks (10.8% vs 7.7%) than the cohort without PHTN (p<0.001). The PHTN group often consisted of higher rates of diabetics (49.8% vs 46.3%) and smokers (45% vs 43.9%) (all p<0.005). The PHTN cohort had a higher all-cause mortality rate (3.7% vs 2.6%), often required home health care (26.7% vs 21.3%), transfers to other care facilities (23.4% vs 21.7%), with prolonged hospital stays (median 4 vs 3 days), and had higher hospital costs (all p<0.005). A significant decline in morbidity and mortality was noted temporally among males, females, and whites, but not in black, hispanic, and asian populations.

Conclusions:
PHTN is strongly associated with morbidity and mortality in geriatric patients with a prior history of revascularized MI. Prospective studies on such patients with long-term follow-up are warranted to establish trends and disparities among different populations and prevent worse outcomes.
Abstract 13166: Proteomic Pathways Across Ejection Fraction Categories in Heart Failure: An Exscel Substudy
Authors: Peters Anthony E , Nguyen Maggie , Green Jennifer , Pearson Ewan , Buse John , Sourij Harald , Hernandez Adrian F , Sattar Naveed , Holman Rury , Mentz Robert J , Shah Svati H
Published: June 2023

Background:
Ejection fraction (EF) is a key component of heart failure (HF) categorization, including the newly-proposed HF with mildly reduced EF (HFmrEF) category. The biologic basis of HFmrEF, as an entity distinct from HF with preserved EF (HFpEF) and reduced EF (HFrEF), has not been substantiated.

Methods:
The EXSCEL trial randomized participants with type 2 diabetes to once-weekly exenatide (EQW) vs. placebo. In participants with prevalent HF, we profiled ~5000 serum proteins. Principal component analysis (PCA) and ANOVA (FDR p<0.1) were used to determine differences in factors and individual proteins between three EF groups, as documented in EXSCEL (EF>55% [HFpEF], EF 40-55% [HFmrEF], EF<40% [HFrEF]). Cox proportional hazards was used to assess relationships between baseline proteins and changes in protein level with incident HF hospitalization.

Results:
Of 1199 EXSCEL participants with prevalent HF, 284 (24%), 704 (59%) and 211 (18%) had HFpEF, HFmrEF and HFrEF, respectively. Eight PCA protein factors and 221 individual proteins within these factors differed significantly across the 3 groups. Levels of the majority of proteins (83.3%) demonstrated concordance between HFmrEF and HFpEF, but higher levels in HFrEF, including the domain of extracellular matrix,
e.g.
COL28A1, tenascin C [TNC]; p<0.0001. A minority of proteins (1%) were concordant between HFmrEF and HFrEF including matrix metalloproteinase-9 (p<0.0001). Baseline levels of 94% of the 221 significant proteins were associated with incident HF including domains of extracellular matrix (COL28A1, TNC), angiogenesis (ANG2, VEGFa, VEGFd), myocyte stretch (NTpro-BNP), and renal function (cystatin-C). Change in levels of 18 of these proteins from baseline to 12 months (including increase in TNC) predicted subsequent HF (p<0.05). TNC levels were reduced by EQW compared with placebo (p<0.0001).

Conclusions:
In this large clinical trial, we found that most proteins were similar between HFmrEF and HFpEF. A key ECM protein, tenascin C, showed this relationship, and baseline level and change in tenascin C predicted HF and changed beneficially with EQW. These results suggest that HFmrEF is more biologically similar to HFpEF and highlight prognostic and modifiable biomarkers that vary by EF.
Abstract 13171: Cardiac Rehabilitation and COVID-19: Nationwide Declines in Access and Participation Among Medicare Beneficiaries
Authors: Varghese Merilyn S , Beatty Alexis , Sperling Laurence S , Fonarow Gregg C , KETEYIAN Steven J , McConeghy Kevin W , Penko Joanne , Song Yang , Yeh Robert W , Figueroa Jose F , Wu Wen-Chih , Xu Jiaman , Kazi Dhruv S
Published: June 2023

Introduction:
The effect of the COVID-19 pandemic on availability of and participation in cardiac rehabilitation (CR) participation is unknown.

Methods:
We used Medicare Fee-for-Service claims, American Hospital Association surveys, and Rural Urban Commuting Area codes to evaluate CR center availability and CR participation (01/2019-12/21).

Results:
Medicare beneficiaries participated in a mean ± SD of 56,898 ± 2,046 CR sessions per month from 01/2019 - 02/2020. Immediately after the announcement of the public health emergency in 03/2020, CR sessions declined by 93% (to 3,989 sessions in 04/2020) (Figure). The monthly CR sessions recovered gradually through 12/21, but CR participation remained 17% lower than pre-pandemic levels (54,730 ± 2,340 sessions/month in Q1 2019 vs. 45,209 ± 326 sessions/month in Q4 2021, p<0.01). Prior to the pandemic, Medicare beneficiaries received CR at 2,631 ± 8 CR centers. Only 688 centers were in operation in 04/2020 (a 74% decline from pre-pandemic levels), with slow and incomplete recovery in the following months. The number of CR centers in 12/2021 was 5% lower than pre-pandemic levels (2,620 ± 6 centers available in Q1 2019 vs. 2,485 ± 8 centers available in Q4 2021, p <0.01). Ownership status (private/not for profit, private/for profit and public/municipal), teaching status affiliation (major, minor and none), and location (metro, micro and rural) were not associated with post-pandemic CR center availability.

Conclusions:
The COVID-19 pandemic has been associated with persistent declines in the availability of CR centers and participation in CR sessions among Medicare beneficiaries. Future studies should examine the impact of these closures on health outcomes and equity. Meeting the Million Hearts Initiative’s goal of equitably increasing CR participation will require scalable innovation in CR financing and delivery.
Abstract 13174: Cardio-Metabolic Traits of a Heart Failure With Preserved Ejection Fraction Mouse Model
Authors: Rosas Paola C , Chowdhury Shamim , Kurup Shreya B , Patel Nisha A
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF, EF>50%) syndrome is often associated with hypertension, hyperlipidemia, obesity, and diabetes. Morbidity and mortality in patients with HFpEF are similar to those with heart failure with reduced ejection fraction, however therapies are scarce. Mouse models used to understand sarcomere dysfunction in HFpEF and to identify new targets are needed. In this study we challenged young mice with volume overload and metabolic perturbations induced by high fat diet (HFD) to harbor the conditions of HFpEF.

Methods:
C57BL/6N 16-weeks old female and male mice were treated with subcutaneous pellets of controlled released DOCA (Deoxycorticosterone Acetate, 0.71 mg/d), drinking water with 1% saline and HFD for a period of 3 weeks to induce obesity and mild hypertension. Cardiac function was evaluated at baseline (before treatment) and 2 and 3 weeks after treatment. Body weight, % fat mass, %lean mass, glucose tolerance test, and lipid profile were also evaluated at baseline and 3 weeks after treatment.

Results (Table): Treatment induced diastolic dysfunction measurable by echocardiography at 3 weeks with slower peak myocardial relaxation velocity (e’), increased peak blood inflow velocity at early diastolic filling E/e’ ratio, increased E/A ratio, and increased isovolumetric relaxation time (IVRT). Meanwhile ejection fraction is preserved. As expected HFD feeding elicited body weight increase with increased fat mass accumulation associated with decreased lean mass, glucose intolerance and hypercholesterolemia.

Conclusions:
This study describes a mouse model of HFpEF that only requires 3 weeks of treatment with DOCA, 1% saline drinking water and HFD. This model reproduces the most common comorbidities of HFpEF such as diastolic dysfunction, obesity, glucose intolerance, and hypercholesterolemia, and may be used to understand the molecular pathophysiology of HFpEF.
Abstract 13176: Overexpression of BANF1 is Linked to Cardiac Pathologies in Progeria Patients
Authors: Perales Selene G , Sigamani Vinoth , Ulaganathan Thennavan P , RAJASINGH SHEEJA , Johnson Rajasingh
Published: June 2023

Introduction:
Hutchinson-Gilford progeria (HGP) is a genetic disorder caused by a single nucleotide mutation in the Lamin A gene. This mutation causes the production of the abnormal lamin A protein called progerin. Children affected by this disorder age rapidly and die at an early age, mostly from cardiac pathologies. Another similar progeroid syndrome is Nestor-Guillermo progeria, in which the patients exhibit accelerated aging but have a longer life span. This latter syndrome is caused by a mutation that silences the BANF1 gene.

Hypothesis:
We hypothesize that BANF1 is linked to cardiovascular disease in Hutchinson-Gilford progeria patients. This gene could be targeted to reduce cardiac pathologies and increase the lifespan of patients with HGP.

Methods:
We obtained skin fibroblasts from two HGP patients and their respective parents from the Progeria Foundation. We successfully reprogrammed the fibroblasts into induced pluripotent stem cells by a safe non-viral method and further differentiated them into induced cardiomyocytes (iCMCs). Then, we performed multiple analyses to compare the iCMCs of the patients, their parents, and control iCMCs.

Results:
Through in-silico protein analysis, we were able to identify a relationship between nuclear lamina proteins and BANF1, which is also correlated to cardiac-specific proteins GATA4 and NKX2.5 (
Figure A
). Additionally, through qPCR (
Figure B
) and Western Blot (
Figure C
) analyses, we identified a significant difference in BANF1 expression between the progeria patient iCMCs and the other iCMCs. BANF1 was overexpressed in patient iCMCs, whereas, it had normal expression in patient fibroblasts when compared to control cells.

Conclusions:
We believe that BANF1 could be a good target for future therapeutic approaches to minimize cardiac pathologies in HGP patients and extend their lifespan.
Abstract 13203: Cardiovascular Health in Cardiac Rehabilitation: Applying the American Heart Association Life's Simple 7 in a Center-Based Cohort
Authors: Chacin Suarez Audry , Brewer LaPrincess , Abraham Helayna M , Olson Thomas P
Published: June 2023

Introduction:
Cardiac rehabilitation (CR) is a comprehensive secondary cardiovascular disease (CVD) program which integrates structured lifestyle interventions to reduce morbidity and mortality. The Life’s Simple 7 (LS7) is an objective measure of cardiovascular health (CVH) which incorporates health-promoting behaviors and clinical factors however, it has not been rigorously evaluated in the CR setting.

Methods:
Retrospective cohort study of 937 patients who attended center-based CR at Mayo Clinic from Jan 2018 -Sept 2020. Patient characteristics and LS7 component metrics at baseline (pre-CR) and completion (post-CR) were collected: 3 clinical factors (blood pressure [BP], cholesterol, and hemoglobin A1c [HbA1c]), and 4 health behaviors (smoking, body mass index [BMI], physical activity [PA] and diet). LS7 score was computed as a composite of each LS7 component by assigning 2-points for ideal, 1-point for intermediate, or 0-points for poor CVH ranging from 0-14 points. LS7 score was further categorized as poor 0-6, intermediate 7-8 and ideal 9 -14.

Results:
Patients were 64±13 years old, 34% were female, and attended a mean of 11±12 CR sessions,
Table 1.
At baseline, the LS7 components with the highest proportion within the poor category were HbA1c (201/495, 41%) and BMI (465/936, 50%),
Table 2.
From pre to post-CR, there was a reduction in proportion of patients classified within the poor category for each LS7 component except HbA1c (
Figure 1
), and the proportion of patients with LS7 scores in the ideal range increased from 6.4% to 19% (P<0.001). There was a statistically significant improvement in LS7 score from 5.5±1.8 to 6.7± 2.4 (+Δ1.6±2.4, P<.0001),
Table 2
.

Conclusions:
Patients attending CR demonstrated an improvement in LS7 score and almost all LS7 components suggesting an overall positive impact of CR on CVH. Further research is needed to better understand the impact of the individual LS7 components on CV outcomes in diverse populations participating in CR.
Abstract 13213: Performance of a Modified RAISE Score to Screen for Cardiac Amyloidosis in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Zenses Anne-Sophie , Bechard Stephanie , Fontaine Valérie , Mansour Mohamad J , Remillard Emilie , Carrier Zoe , Forcillo Jessica , Masson Jean-Bernard , Potvin Jeannot , Gobeil Jean-François , Juneau Daniel , Ribeiro Paula A , Argentin Stefania , Tournoux Francois
Published: June 2023

Background:
A high prevalence of cardiac amyloidosis (CA) can be found in specific populations such as TAVI [transcatheter aortic valve implantation] referrals. However, CA diagnosis is complex and often missed. Several institutions have engaged active chart review by a multidisciplinary clinical committee (MCC) - a highly labor intensive process - to identify patients at risk for CA.

Objective:
To assess whether the recently published RAISE score (Remodeling, Age, cardiac Injury, Systemic and Electrical abnormalities) could be a substitute to optimize the MCC based pre-screening process in a TAVI population.

Methods:
Our institutional MCC reviewed the medical chart of all patients who underwent TAVI in the past 3 years and appreciated the utility of scintigraphic screening. The decision to screen or not was based on the presence of red flags and the anticipated clinical benefice. The original RAISE score was slightly modified (mRAISE,
Figure
) to facilitate its use in our TAVI patients, for whom CA suspicion had never been raised. A patient with a score ≥3 was considered at high risk for CA (best cutoff previously published). The mRAISE score was compared to the MCC’s decision using a Cohen’s k.

Results:
Among 239 included patients (79±7y, 55% male), an mRAISE score ≥3 was found in 47 (20%), of whom the MCC suggested screening to only 25 (53% agreement), most of the remaining 22 being asymptomatic following TAVI. Of 192 patients (79%) with an mRAISE score <3, the MDC decided on “no screening” for 180 (94% agreement) and “screening” for the other 12; 3 patients refused and 9 had a negative screening. When compared with the MCC’s decision, global agreement of the mRAISE score was 86% with k=0.52 (
Figure
).

Conclusions:
The mRAISE score is not a perfect substitute for a MCC but rather an ideal pre-screening tool to optimize efficiency. If calculated prior to MCC meetings, an mRAISE score <3 can dramatically reduce the number of medical charts that need extensive review (>3/4 in our cohort).
Abstract 13221: A Multidisciplinary Approach to Transvenous Lead Extraction in the Setting of a Large Patent Foramen Ovale
Authors: Keen Susan , Dhande Mehak , Barakat Amr F , Toma Catalin , Smith Anson J , Estes N A , Shalaby Alaa
Published: June 2023

Introduction:
Increasing cardiovascular implantable electronic devices (CIED) implantation has been associated with a rising incidence of CIED infection. Treatment includes targeted antimicrobial therapy and device hardware removal although larger lead vegetations have historically undergone surgical removal. As many CIED recipients are at high surgical risk, there is growing need for transvenous approaches for safe debulking of vegetation mass.

Case:
An 80-year-old man with a history of ischemic cardiomyopathy and an indwelling dual chamber implantable cardioverter defibrillator (ICD) for 17 years with previous appropriate shocks was found to have
Enterococcus faecalis
bacteremia. Transthoracic echocardiography revealed a 3 cm vegetation on the right ventricular lead involving the tricuspid valve in addition to a large patent foramen ovale (PFO). He was started on intravenous antibiotics. Blood cultures revealed no growth.

Decision-making:
The large-sized vegetation in presence of a PFO posed a risk for pulmonary or systemic embolization from transvenous lead extraction. A multidisciplinary approach was developed which included temporary PFO occlusion, thrombus aspiration with the Inari FlowTriever thrombus aspiration system, and transvenous laser lead extraction (Figure 1). No residual material remained and the Amplatzer was retrieved. Cultures from the pocket, lead tips, and vegetation were collected. The vegetation culture grew
E. faecalis.
He underwent subcutaneous ICD implant six weeks later following antibiotic therapy.

Conclusions:
Vegetation suction with a simple handheld device can be safe and effective for vegetation removal in high-risk cases. Furthermore, temporary PFO occlusion can be performed during vegetation debulking and device extraction. These management strategies may gain wider application with an increasing need for lead extraction in older patients with comorbidities that preclude surgical candidacy.
Abstract 13233: Covid Related Thrombus or Vasculitis?
Authors: Rashmi Prama , Urja Prakrity
Published: June 2023

COVID is associated with cardiovascular manifestations. It worsens the pre-existing cardiovascular diseases, and newly diagnosed cardiovascular diseases are being reported with it. In our abstract we present a case with unusual cardiac manifestation with COVID.

63-years-old, covid positive male with hypertension, hyperlipidemia and coronary artery disease with prior RCA stent was admitted for inferior STEMI.The angiogram showed instent stenosis, with distal vessels narrowing. Stent was placed in RCA. Despite this, he had persistent chest pain and ST elevation, so he was taken back to Cath lab. It confirmed patent stent. For distal vessel narrowing with ongoing pain intra-aortic balloon pump was placed. Aggrastat and heparin was continued. At the time of discharge, he had ongoing dyspnea and chest pain, which was thought to be associated with COVID. He was readmitted in six days for pericardial effusion with constriction and echocardiographic finding of tamponade. He had elevated inflammatory markers and liver enzyme. With recent COVID infection, elevated inflammatory markers, echo findings and known distal coronary artery narrowing there was a concern of vasculitis and pericarditis. He was started on steroid and colchicine with significant improvement.

COVID can cause direct myocardial injury or indirect injury due to altered myocardial demand-supply. The pericardial involvement is associated with heightened inflammation and increased vascularity. Interestingly, our patient who initially presented as ACS had resolution of symptoms with steroids. Could ACS symptoms not resolving with antiplatelets and stenting be a part of inflammatory picture of COVID? In post-COVID autopsy and surgical tissue diffuse lymphocytic endotheliitis and apoptotic bodies are seen in the vascular beds. Vasculitis lesion in skin and Kawasaki’s disease is reported in adolescents and children. However, adult-onset vasculitis is still to be studied.
Abstract 13240: The Relationship Between History of Valve Surgery and Heart Failure Event in Japanese Atrial Fibrillation Patients: The Fushimi Af Registry
Authors: DOI KOSUKE , Ishigami Kenjiro , Ikeda Syuhei , Yoshizawa Takashi , Hamatani Yasuhiro , Ide Yuya , Fujino Akiko , Ishii Mitsuru , Iguchi Moritake , Ogawa Hisashi , Masunaga Nobutoyo , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: June 2023

Background:
We previously reported that valvular heart disease (VHD) was associated with an increased risk of hospitalization for heart failure (HF) in Japanese atrial fibrillation (AF) patients. However, the association of history of surgery for VHD with HF hospitalization remains unknown.

Method: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of July 2021. In the entire cohort, 747 patients had VHD. We divided them to surgery group (n=182) and non-surgery group (n=565). We compared clinical characteristics and incidence rates of HF hospitalization between two groups.

Result: Patients who received valve surgery were younger (72.0 years vs. 78.0 years, p<0.001), had lower systolic blood pressure (118 mmHg vs. 123 mmHg, p=0.02) and pulse rate (75.5 bpm vs. 79.1 bpm, p=0.003), more often paroxysmal type (46.7% vs. 31.0%, p<0.001), less likely to have hypertension (51.1% vs. 66.2%, p<0.001) and had lower CHADS2 score (2.09 vs. 2.55, p<0.001) than non-surgery group. Body weight, sex, prior HF, chronic kidney disease and prescription data were comparable between two groups.

During the median follow-up of 1,679 days, the incidence rate of HF hospitalization was lower in surgery group than non-surgery group (2.58% vs. 4.43% per person-year, respectively, log rank p=0.001). On multivariate Cox regression analysis, history of surgery was not significantly associated with a lower risk of HF hospitalization (adjusted hazard ratio 0.76; 95% confidence interval 0.52-1.12, p=0.16).

Conclusion:
The incidence rate of HF hospitalization was lower in patients with valve surgery than non-surgery group. However, history of valve surgery was not independently associated with a lower risk of HF hospitalization in Japanese AF patients.
Abstract 13248: The Association of Serial Measures of Plasma Trimethylamine N-Oxide With Incident Chronic Kidney Disease and Renal Function Decline Among Older Adults: The Cardiovascular Health Study
Authors: Wang Meng , Tang Wai Hong W , Otto Marcia D , Lee Yujin , Lemaitre Rozenn N , Fretts Amanda M , Sootedehnia Nona , Sitlani Colleen , Budoff Matthew , DIDONATO JOSEPH , Wang Zeneng , Psaty Bruce M , Siscovick David S , Sarnak Mark J , Mozaffarian Dariush , Hazen Stanley L
Published: June 2023

Introduction:
Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes renal tubulointerstitial fibrosis and kidney injury. Yet, little is known about prospective associations between TMAO and renal outcomes.

Hypothesis:
Higher plasma TMAO levels are prospectively associated with higher risk of incident chronic kidney disease (CKD) and greater renal function decline.

Methods:
We included 4,131 US adults from the Cardiovascular Health Study, a community-based cohort, with normal baseline renal function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73m
2
). TMAO was measured using liquid chromatography-mass spectrometry at baseline and year 7. Creatinine and Cystatin C were measured 4 times during serial follow-up and used to compute eGFR. Incident CKD was defined by eGFR (decline ≥ 30% plus eGFR<60 at a follow-up visit) or presence of CKD hospitalization ICD codes. Time-varying Cox models assessed how serial TMAO measures related to incident CKD, adjusting for sociodemographic, lifestyle, diet, and CVD risk factors. Linear regression models assessed how baseline TMAO related to annualized eGFR change in 3,997 participants with at least one follow-up eGFR measure.

Results:
During a median follow-up of 14 years, 1,136 participants developed CKD. There was a non-linear dose-response relationship of TMAO with CKD incidence: higher TMAO levels were associated with higher risk of incident CKD with a plateauing of risk above the ~75
th
percentile of TMAO levels (top
Figure
). Higher baseline TMAO levels were also associated with greater annualized eGFR decline (P-linearity=0.004. bottom
Figure
) after adjusting for baseline eGFR and other covariates.

Conclusions:
In this community-based cohort of older US adults, higher serial measures of plasma TMAO were associated with a higher risk of incident CKD and a greater rate of annualized renal function decline.
Abstract 13253: Regionalizing Non-Pulmonary Vein Triggers for Atrial Fibrillation Using Timing and Activation Pattern of Intracardiac Electrograms From Two Linear Decapolar Catheters
Authors: Thind Munveer , Arceluz Martin , Lucena Padros Irene , Kubala Maciej , Dhakal Bishnu P , Bode Weeranun D , Cerantola Maxime , Mirwais Maiwand , Bush Kelvin , Guandalini Gustavo , Hyman Matthew C , Lin David , Deo Rajat , Nazarian Saman , Tschabrunn Cory M , Schaller Robert D , Epstein Andrew E , Supple Gregory E , Frankel David S , Santangeli Pasquale , Callans David J , Marchlinski Francis E
Published: June 2023

Introduction

Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation (PVI) reduces atrial fibrillation (AF) recurrence. However, NPVTs are often single atrial ectopic beats with surface P wave obscured, making regionalization a challenge. We aimed to construct an algorithm to regionalize the site of origin of NPVTs using exclusively intracardiac electrograms from two standardly positioned linear decapolar catheters positioned 1) in the postero-lateral right atrium, along crista terminalis (CT) with distal bipole pair extending into SVC, and 2) in the coronary sinus (CS), with proximal bipole pair at CS ostium.

Methods

In 42 patients with AF, after PVI, we paced at 15 sites where NPVTs commonly arise (Figure 1). For each pacing site we analyzed activation sequence of the CS catheter electrogram (simultaneous/chevron/inverse chevron/distal-proximal/proximal-distal) and the timing (CSCT time) between the earliest electrograms from the two decapolar catheters. Negative CSCT time indicates CT catheter electrogram is earliest, positive indicates CS catheter electrogram is earliest (Figure 2, lower right).

Results

In this patient cohort (71% male, 57% persistent AF, 52% left atrial dilation), our algorithm was able to group the 15 pacing sites, into 7 clinically useful and distinct regions with high precision (positive predictive value range 81-99%, Figure 2).

Conclusions

An algorithm defined by the activation sequence and timing of electrograms from two linear multipolar catheters allows for accurate regionalization of NPVTs. This may be used to expedite identification of a region of interest to guide further focused detailed mapping of AF NPVTs.
Abstract 13254: Klotho Suppresses Endothelial-to-Mesenchymal Transition in the Aorta of Mice With Chronic Kidney Disease by Inhibition of Endothelial Senescent Activity
Authors: Yao Qingzhou , The Erlinda , Zhai Yufeng , Ao Lihua , Fullerton David , Meng Xianzhong
Published: June 2023

Background:
Klotho is an anti-aging protein expressed primarily in the kidney and vasculature. Chronic kidney disease (CKD) results in hyperphosphatemia. We reported that high levels of phosphate downregulate Klotho expression in vascular cells. Endothelial-to-mesenchymal transition (EndMT) in arteries promotes the development of atherosclerosis, and CKD is a significant risk factor for atherosclerosis. However, the impact of CKD on EndMT in arteries is unclear and whether Klotho insufficiency plays a role in the mechanism underlying vascular EndMT remains unknown. This study tested the
hypothesis
that Klotho insufficiency associated with CKD induces senescence in arterial endothelial cells to upregulate EndMT.

Methods and Results:
We developed a CKD model in C57/BL6 mice (5-6 months old) on AIN-76A diet and treated with adenine and calcitriol.
CKD was confirmed by markedly elevated blood levels of creatinine and phosphate, as well as by renal tubular damage. En face immunofluorescence staining of aorta and image quantification revealed that the levels of biomarkers of senescence (P21) and EndMT (vimentin) were greater, while Klotho levels were lower, in the aortic arch endothelial cells of CKD mice compared to sham control mice. P21 and vimentin were co-localized in a greater number of endothelial cells in the aortic arch of CKD mice. High phosphate treatment upregulated the levels of P21 and vimentin and reduced the levels of Klotho in both primary human and mouse aortic endothelial cells, and knockdown P21 attenuated EndMT induced by high phosphate. Recombinant Klotho suppressed both senescence and EndMT in primary human aortic endothelial cells. Further, prolonged treatment of CKD mice with recombinant Klotho attenuated endothelial senescence and EndMT in the aortic arch.

Conclusion:
Klotho insufficiency associated with CKD promotes endothelial senescence and EndMT in aorta. High phosphate is capable of inducing endothelial senescent change that provokes EndMT. Administration of recombinant Klotho or upregulation of Klotho expression may have therapeutic potential for suppressing pro-atherosclerosis activity in large arteries by prevention of endothelial senescence and resultant EndMT.
Abstract 13256: Prognosis of Congestive Heart Failure Due to Chagas Disease in Women and Men
Authors: Mansur Antonio de Padua , del Carlo Carlos H , Bocchi Edimar A , Pereira-Barretto Antonio C
Published: June 2023

Introduction:
Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of congestive heart failure (CHF) in Latin America and carries a high morbidity and mortality burden. Previously, it was believed that there was no epidemiological and clinical evidence of a gender-associated risk of death in patients with CCC.

Hypothesis:
to analyze the mortality of congestive heart failure due to CCC in women and men.

Methods:
From February 2017 to September 2020, we followed a cohort of patients with CHF due to CCC in a single-center outpatient clinic. Serologic tests defined Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed with the Kaplan-Meier method and Cox proportional hazards methods.

Results:
We studied 733 patients, mean of 61.4 ± 12.3 years, and 381 (52%) males. At baseline, women were older (63.0±11.9 vs. 60±12.4 years; p=0.01), had a higher prevalence of CKD (9.7 vs. 5.1%; p=0.002), higher mean left ventricular ejection fraction (LVEF) (44.5±14.6% vs. 37.3±14.8%; p<0.001), and a lower left ventricular diastolic diameter (LVDD) (56.7±8.9 vs. 62.4±9.4 mm; p<0.001). Over a 3-years follow-up period, 294 patients died being 168 (57%) men and 126 (43%) women (log-rank; p=0.002). Women had more implantable pacemakers (26.1% vs. 16.5%; p=0.002) and men more implantable cardioverter-defibrillators (20.7% vs. 12.5%; p=0.003). Heart transplants occurred in 10.8% of men and 7.4% of women (p=NS). Cox regression for death adjusted for age, sex, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation, and LVEF showed men (HR=1.4; 95%CL:1.1-1.8), previous stroke (HR=2.4; 95%CL:1.5-3.6), diabetes (HR=2.0; 95%CL: 1.3-3.1), and CKD (HR=1.8; 95%CL:1.3-2.6) as the main predictors of death.

Conclusions:
women had a better prognosis than men. Treatment of comorbidities will significantly reduce the death rate in CHF due to CCC.
Abstract 13266: Sex Specific Differences in the Gut Microbiome in Patients With Pulmonary Arterial Hypertension
Authors: Blake Madelyn , Moutsoglou Daphne , Khoruts Alexander , Weir Edward K , Thenappan Thenappan
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) patients exhibit sexual dimorphism in pulmonary vascular remodeling and right ventricular (RV) dysfunction. While female PAH patients have severe pulmonary vascular remodeling, male PAH patients have worse RV function. Inflammation, a key component of PAH pathobiology, has been implicated as a potential mechanism for sexual dimorphism. Gut dysbiosis causes systemic inflammation. However, it is unknown whether gut dysbiosis contributes to sexual dimorphism in PAH.

Hypothesis:
There are sex-specific differences in the gut microbiome and microbial metabolites of PAH patients.

Methods:
16S ribosomal ribonucleic acid gene sequencing was performed on stool samples from PAH patients (n=73). Markers of inflammation and circulating microbial metabolites were measured using plasma samples.

Results:
There was no significant difference in the Shannon diversity indices or species richness (Chao1 indices) between the gut microbiomes of male and female PAH patients. Moreover, principal component analysis of pairwise Bray-Curtis dissimilarity indices revealed no distinct microbiome compositions dependent on sex. There was no difference in serum claudin-3, a marker of gut permeability, and serum interleukin 6 levels between male and female PAH patients. When examining microbial metabolites, including trimethylamine N-oxide, short chain fatty acids, and secondary bile acids, no sex-specific differences were observed. Linear discriminant analysis of effect size revealed that there were no taxonomic differences based on sex.

Conclusions:
Male and female PAH patients do not possess distinct differences in their gut microbiomes or metabolites. There are also no sex-specific taxonomic differences. These findings do not support our hypothesis that gut dysbiosis may serve as a possible explanation for the sexual dimorphism observed in PAH.
Abstract 13269: Effects of Nicotine-Containing Product Challenges on Interleukin-6 Pathway Expression in Human Pluripotent-Derived Arterial Endothelial Cells: The Clues Study
Authors: Tattersall Matthew C , Esnault Stephane , Stewart Ron , Swanson Scott , Steill John , Korcarz Claudia E , Hansen Kristin M , Baker Timothy B , Stein James H
Published: June 2023

Background:
Electronic nicotine delivery devices (ENDs) induce interleukin-6 (IL-6) pathway expression in airway epithelial cells, but their systemic effects on arterial endothelial cells (AECs) are unknown. We hypothesized differential expression (DE) of IL-6 pathway genes by human pluripotent-derived AECs exposed
in vitro
to participant serum drawn before and after use of ENDS by chronic vapers, use of combustible cigarettes by smokers, and no product use by controls.

Methods:
For this pilot study, we randomly selected 30 participants from the CLUES Study: 10 exclusive vapers (exhaled carbon monoxide [CO] <5 ppm, + urine NicCheck I), 10 exclusive smokers (CO >5 ppm, + urine), and 10 non-vaping/non-smoking controls (CO <5 ppm, negative urine). We generated purified populations of AECs (H9 CPTC C13 derivative human embryonic stem cell line) and exposed them for 6 hours to 50% concentrated participant serum drawn before and 15’ after a product use challenge. Total RNA was sequenced on a NextSeq 2000. The DESeq2 suite characterized DE with an
a priori
focus on genes in the IL-6 biosynthetic pathway gene ontology set. Z scores of normalized log2 gene expression values were determined and expressed as heat maps (Figure). Gene Set Variational Analysis (GSVA) was used to interrogate for enriched gene sets. P values were not adjusted for multiple hypothesis testing and are exploratory.

Results:
Vapers were a mean (SD) 28.9 (8.1) years old (30% female), smokers were 38.3 (11.6) years old (40% female), and controls were 33.6 (17.7) years old (50% female). Compared to controls, vapers had increased expression of the IL-6 pathway at baseline (p=0.004), but smokers did not (p=0.38). Following product use, vapers (p=0.0009) but not smokers (p=0.79) had increased expression of genes in the IL-6 biosynthetic pathway (Figure).

Conclusion:
Chronic vapers, but not smokers, may have increased expression of genes in the IL-6 pathway prior to product use with further increases afterwards.
Abstract 13282: Towards a Decision Support Tool for Opioid Administration and Sedation Management in the Pediatric Cardiac Intensive Care Unit
Authors: Emani Sivaram , Sperotto Francesca , Delgado Marlon , Zhu Lin , Santillana Guzman Mauricio , Kheir John
Published: June 2023

Introduction:
Opioids are commonly used to treat pain and agitation in the cardiac intensive care unit. However, responsiveness to opioids in pediatric patients is poorly understood, and few guidelines exist for personalized management of sedation. This leads to probable overprescription of opioids in the pediatric ICU, which can extend length of stay and have negative long-term health consequences. In this work, we build a decision support tool to predict a patient’s response to an opioid bolus measured by the state behavior scale (SBS), using available patient data at the time of administration.

Methods:
We built a dataset including all individual doses of morphine administered to patients admitted to the CICU between 2011-2020. Patients missing critical hemodynamic or SBS data were excluded from the analysis. The change in SBS score before and after morphine administration was converted to a binary outcome, where a decrease in SBS score was considered to be favorable (A). A LASSO regression model was trained to predict SBS response. The predictors utilized in the model included demographics, hemodynamic data, SBS score measurements before morphine, concomitant drug infusions/boluses and morphine response to prior doses. The model was trained on 80% of data and evaluated on 20%.

Results:
Of 197,242 intravenous boluses, 66,195 boluses administered to 6,021 patients (median age 7.2 mo) were included. The median change in SBS score was 0 (IQR -1 - 0) with 33% of administrations classified as favorable responses. The model coefficients are shown in (B). The model predicts 74% of unfavorable morphine responses with 95% confidence, AUC = 0.899 (C).

Conclusions:
Nearly three-quarters of ineffective responses to morphine can be predicted with 95% confidence using the prediction models developed. Such models could substantially reduce morphine over-administration for critically ill patients in the pediatric cardiac ICU.
Abstract 13283: Utility of Ultrasound-Guided Measurements of Carotid Intima Media Thickness and Achilles Tendon Thickness in Patients With Familial Hypercholesterolemia
Authors: Echeverry Tatiana , Anthony Jamal , Fishberg Robert D
Published: June 2023

Introduction:
Ultrasound-guided measurement of carotid intima-media thickness (CIMT) can be used as a marker to predict future risk of atherosclerotic cardiovascular disease. Achilles tendons are the most common sites of xanthoma accumulation and can serve as a diagnostic index for patients with familial hypercholesterolemia (FH). We report a case of a patient with FH on PCSK9 inhibitor, who was followed up over the course of five-years to monitor the impact of the medication on CIMT and Achilles tendon thickness (ATT).

Hypothesis:
PCSK9 inhibitors are associated with reduction of carotid artery plaque and regression of tendon xanthomas.

Methods:
In a prospective study, at Overlook Medical Center in New Jersey, we followed up a 27-year-old patient with FH on PCSK9 inhibitor and high-dose statin diagnosed in 2006. After CABG, patient underwent CIMT and ATT in 2017, 2019 and at the five-year follow up in 2022.

Results:
In 2017, patient underwent ultrasound of the bilateral common carotids showed CIMT to be 0.91mm on right and 0.78mm on left and ultrasound of bilateral Achilles tendon showed ATT to be 0.91cm on right and 1.11cm on left. In 2019, ultrasound of bilateral common carotids showed CIMT to be 0.5mm on right and 0.57mm on left (mean CIMT reduction of 38%). Ultrasound of bilateral Achilles tendon showed ATT to be 1.04cm on the right and 0.98cm on the left (no significant change). In 2022, patient presented for the 5-year follow up, ultrasound of bilateral common carotids showed CIMT to be 0.55mm on right and 0.54 mm on left (no significant change) Ultrasound of bilateral Achilles tendon showed ATT to be 1.12cm on the right and 1.02cm on the left (no significant change).

Conclusions:
This case highlights the significant reduction in carotid artery plaque burden within the first two years of treatment with PCSK9 inhibitors. However, CIMT did not have a significant change after the five-year follow up. In addition, the patient didn’t have any significant changes in the Achilles tendon thickness throughout the five-years of treatment. This case illustrates how ultrasound-guided measurement of CIMT may help stratify ASCVD progression and quantify the effect of PCSK9 inhibitor on atherosclerotic plaque.
Abstract 13286: Symptoms in Heart Failure Improve With More Intense Physical Activity
Authors: Auld Jonathan , Thompson Frances Elaine , Stempien-Otero April , Dougherty Cynthia M
Published: June 2023

Purpose.
RCTs have demonstrated the benefits of exercise in heart failure (HF) including improved functional status and quality of life, with fewer hospitalizations. Little is known about how changes in physical activity (PA) over time may influence physical and psychological symptoms. This study examined the extent to which changes in PA over time were associated with changes in physical and psychological symptoms in HF.

Methods.
A secondary analysis was conducted using an RCT of exercise in HF patients (N=86) who received an initial ICD. Data were collected at baseline and 2 months. Physical activity was measured over 5 consecutive days using the StepWatch PA Monitor (Orthocare Innovations
TM
) for total PA (mean steps/day) and intensity (mean steps/min for most intense 30 minutes/day). Other measures included: physical symptoms (Patient Concerns Assessment (PCA); fatigue and pain (SF-36 Vitality & Bodily Pain subscales, respectively), and symptoms of depression (Patient Health Questionnaire-9, PHQ9) and anxiety (State-Trait Anxiety Index, STAI). Multivariate regression was used to examine for associations between increased and decreased PA and changes in physical and psychological symptoms, adjusting for age, co-morbidities, body mass index, ejection fraction (EF), and study group.

Results.
Patients were male (82%), 55.3±12.1 years of age, white (79%), with multiple co-morbidities (Charlson Co-morbidity: 2.1±1.3), BMI of 30.0±5.1, with reduced EF (31.0±10.1%). An
increase
in PA intensity from baseline to 2 months was associated with significant improvement in psychological symptoms (PHQ9:β= -0.13, p=0.030; STAI:β= -0.26,p=0.026) and fatigue (β= 0.55,p=0.023). An
increase
in total PA (steps/day) was associated with improvement in anxiety only (β= -1.23, p=0.045). A
decrease
in PA (total and intensity) was not associated with changes in any symptoms.

Conclusion.
For patients with HF and an initial ICD, increased intensity of PA over 2 months was associated with improved psychological symptoms and reduced fatigue. Decreases in PA (total and intensity) were not associated with symptoms. These findings warrant further investigation as interventions focused on PA intensity rather than quantity may be more effective in reducing symptoms in HF.