bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4138815: Prognostic Implications of Glycemic Variability Assessed by Continuous Glucose Monitoring-derived Coefficient of Variation among Patients Hospitalized for Acute Heart Failure
Authors: Ito Haruyasu , Yukawa Hiroshi , Nakagawa Eiichiro , Nagao Kazuya , YAMADA Chinatsu , tada tomohisa , Kobayashi Yohei , Kanazawa Takenori , Onishi Naoaki , Aida Kenji , Shimamura Kiyotaka , Makita Toshinori , HAYASHI FUJIO
Published: November 2024

Background:
Recent findings indicate that high glycemic variability (GV) could increase the risk of adverse outcomes in patients with cardiovascular disease. With the advances in technology, the utility of continuous glucose monitoring (CGM) has grown during recent years, which can provide valuable information that is not captured by HbA1c. We used the glucose coefficient of variation (CV, calculated as the ratio of standard deviation divided by the mean glucose level) of the obtained CGM data to analyze GV.

Aims:
We aimed to analyze CGM-derived CV as an indicator of GV and to evaluate prognostic implications of CGM-derived CV in patients hospitalized for acute heart failure (HF).

Methods:
Patients hospitalized for HF who had not been diagnosed diabetes were performed 75g-oral glucose tolerance test (OGTT). CV was evaluated using CGM system for at least 72 consecutive hours after being able to have meals stably during hospitalization. The primary outcome was a composite of cardiovascular death or re-hospitalization for HF. Patients were divided into two groups based on the median value of CV.

Results:
We prospectively analyzed 130 patients (mean age: 76±10 years, male 56%) admitted for acute HF. Following the 75g-OGTT, only 21% of the entire cohort exhibited normal glucose tolerance. During the median follow up period of 905 days, Kaplan–Meier curve analysis revealed that the cumulative incidence of the primary outcome event was significantly higher in patients with CV above median than in those with CV less than median (51.7% versus 24.4%, Log-rank P=0.01)(Figure). Multivariate Cox proportional analysis demonstrated that the risk of CV per 1% increment for the primary outcome was significant adjusted for history of diabetes, CGM-derived mean glucose level, and HbA1c level (hazard ratio: 1.06, 95% confidence interval 1.03–1.09).

Conclusions:
CGM-derived CV was associated with long term prognosis of patients hospitalized for HF with or without diabetes.
Abstract 4138953: Salivary Tumor Necrosis Factor-Alpha, Plasma Omega-3 Fatty Acid Index and Coronary Artery Plaque
Authors: Daher Ralph , Ahmad Bushra , Malik Abdulaziz , Alfaddagh Abdulhamied , Welty Francine
Published: November 2024

Background:
Oral inflammation is thought to affect systemic atherosclerosis, but the mechanisms are unclear. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that has been implicated in coronary plaque rupture as well as periodontitis by mediating periodontal destruction and inflammation. Blood levels of the omega-3 fatty acids have been inversely associated with systemic inflammation and coronary plaque volume, but their impact on oral inflammation requires further study.

Objective:
To examine the relationship between salivary levels of TNF-α, plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and coronary plaque.

Methods:
Salivary TNF-α was measured in gingival crevicular fluid in 199 patients with clinical coronary artery disease on statin therapy. Fatty, fibrous and noncalcified coronary plaque volumes were measured using coronary CT angiography. The plasma omega-3 fatty acid index was the sum of EPA and DHA of total plasma fatty acids. Linear regression estimated the association between TNF-α, omega-3 fatty acid index and coronary plaque volumes.

Results:
Mean age was 62.7±7.5 years; mean LDL-C was 78.2±28.9 mg/dL, and median triglyceride was 119 [80.5,165.0] mg/dL. Higher salivary TNF-α was independently associated with a lower plasma omega-3 fatty acid index (Table 1). Moreover, higher salivary TNF-α was independently associated with higher fatty, fibrous, and noncalcified plaque volumes after adjustment for age, sex, BMI, triglyceride, LDL-C, diabetes status, diastolic blood pressure, albumin-to-creatinine ratio, and estimated glomerular filtration rate (Table 2).

Conclusions:
The inverse relationship between salivary TNF-α and the plasma omega-3 fatty acid index and direct relationship with fatty plaque suggests that maintaining high blood levels of omega-3 fatty acids may be beneficial in lowering oral inflammation and amount of fatty plaque, thus, potentially decreasing risk for acute coronary syndromes.
Abstract 4138992: Beta blockers and calcium channel blockers in pre-symptomatic patients with hypertrophic cardiomyopathy: prevalence, discontinuation, and effectiveness
Authors: Bradlow William , Elgui Kevin , Klopfenstein Quentin , Balazard Felix , Trichelair Paul , TOUZOT Maxime , Micsinai Balan Mariann , Van Haelst Paul , Sandler Belinda , Sehnert Amy , Bastien Arnaud , Blizard Perry , RIPOLL-VERA TOMAS , Pericas Pau , Fudim Marat , Balu Suresh , Hintze Bradley , Salah Husam , Patel Manesh , Foucher Aurelie , Charron Philippe
Published: November 2024

Background:
Beta-blockers (BB) and non-dihydropyridine calcium channel blockers (CCB) are first-line therapies for hypertrophic cardiomyopathy (HCM) used both upon symptom onset and for pre-symptomatic patients. However, there is limited evidence supporting their efficacy, particularly from randomized controlled trials.

Aims:
In this study we assessed the prevalence, discontinuation rates, and effectiveness of BB/CCB for NYHA class I HCM patients.

Methods:
Utilizing data from a real world cohort spanning 4 centers, we evaluated BB/CCB effectiveness in NYHA class I patients with HCM. The effectiveness analysis for a composite endpoint (NYHA class worsening and cardiovascular-related hospitalization) was performed independently at each center and an aggregated analysis was performed. NT-proBNP level analysis was performed where longitudinal data was available. Patients initiating therapy during follow-up were compared to untreated controls, adjusting for confounders (duration since HCM diagnosis, left atrial volume index (LAVi), E/e' lateral ratio, medical history, NT-ProBNP levels) using inverse probability weighting and Stürmer trimming. The association between treatment and the risk of composite endpoint was assessed through Cox regression, while mixed models for repeated measures were used for NT-proBNP levels.

Results:
Among the 735 patients, 64% initiated BB/CCB therapy with a 33% discontinuation rate at 4 years. A total of 222 patients with extreme propensity scores were excluded. As shown in Table 1., no benefit from BB/CCB in reducing the composite endpoint risk (HR=1.08, p=0.79) was observed. This was consistent across the different components of the endpoint. Additionally, no benefit in reducing NT-proBNP levels after 1 year was detected (Least Means Square difference=0.02, p=0.79).

Conclusion:
Initiation of BB/CCB for NYHA I HCM patients did not appear to reduce the risk of progression measured by the functional capacity, CV hospitalization and NT-proBNP. Despite the inherent limitation of observational studies, these findings together with the high discontinuation rate of the therapy, underscore the need for further research to validate optimal treatment strategies for pre-symptomatic HCM patients.
Abstract 4139026: Prevalence of Familial Hypercholesteremia (FH) Among Participants in the ACCELERATE Trial: Implications for Opportunistic FH Screening and Prognostication
Authors: Sarraju Ashish , St John Julie , Singh Abhayjit , Knowles Josh , Rodriguez Fatima , Bruemmer Dennis , Cho Leslie , Laffin Luke
Published: November 2024

Background:
Familial hypercholesteremia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD). Although treatable, FH is underdiagnosed. Lipid lowering therapy may mask diagnostic pretreatment LDL-C levels. Participants of ASCVD trials may be enriched for FH, so ASCVD trial enrollment may be a unique contact point to opportunistically diagnose FH.

Hypothesis:
The population of the ACCELERATE trial of evacetrapib and ASCVD outcomes is enriched for FH.

Methods:
ACCELERATE is a phase 3 cardiovascular outcomes trial which randomized 12,092 patients with high-risk vascular disease to receive evacetrapib or placebo. FH was not reported. Using participant-level data, we estimated pretreatment LDL-c using validated corrections based on type and dose of statin therapy. We defined severe hypercholesterolemia as pretreatment LDL-C ≥ 190 mg/dl and FH as severe hypercholesterolemia with total cholesterol > 290 mg/dL in a first or second degree relative, consistent with Simon Broome register criteria. We compared trial prevalence to general prevalence (severe hypercholesterolemia ~7%, FH ~0.4%). We evaluated the adjusted association of severe hypercholesterolemia with the primary trial endpoint of ASCVD events using multivariable Cox proportional hazards regression.

Results:
Data were available for 11,993 participants (99%). The prevalence of severe hypercholesteremia was 15% (1809/11993). The prevalence of FH was 2.1% (255/11993). Pretreatment LDL-C ≥ 190 mg/dL, as compared with pretreatment LDL-C < 190 mg/dL, was significantly associated with a higher incidence of the primary ASCVD trial endpoint (15% vs 13.5% respectively, adjusted hazard ratio 1.19; 95% CI 1.03-1.38, P=0.021;
Figure
).

Conclusion:
In a participant-level analysis of a rigorous, independently adjudicated ASCVD outcomes trial, severe hypercholesterolemia and FH were more prevalent in the trial population than the general population based on pretreatment LDL-C calculation. Severe hypercholesterolemia was significantly associated with higher ASCVD incidence. ASCVD trial enrollment may be a novel high-yield contact point for index FH case identification using simple pretreatment LDL-C calculation.
Abstract 4139074: Clinical characteristics and treatment of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - results from US
Authors: Chan Queenie , Sakhuja Swati , Ochs Andreas , Dhalwani Nafeesa , O'Kelly James , Shannon Erin , PaivadaSilva Lima Gabriel , Avcil Suna , Laufs Ulrich , Jernberg Tomas , Cegla Jaimini , Budoff Matthew , Wong Ian
Published: November 2024

Background:
Early intervention with lipid lowering therapy (LLT) in patients with high cardiovascular (CV) risk before myocardial infarction or stroke may have substantial public health benefits, despite being perceived as less urgent. The effect of evolocumab in this population is being investigated in an ongoing clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]). The current ongoing observational study examines the global burden of a VESALIUS-CV-like population in the REAL-world (“VESALIUS-REAL") in eight regions. We present data here on baseline characteristics and LLT of VESALIUS-CV like patients in the US.

Methods:
Using the eligibility criteria aligned with VESALIUS-CV (
Figure
), data were extracted from HealthVerity medical and pharmacy claims (2016-2023). A two-year observability period was required before index date; therefore, the first possible cohort entry was on January 1, 2018.

Results:
There were 518,852 VESALIUS-CV like patients with median age of 72 years (Q1-Q3: 64-79 years) and 56% were female (
Table
). Overall, 43% had coronary artery disease and 34% had high-risk diabetes mellitus (DM). Median low density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol and apolipoprotein B were 114 (Q1-Q3: 97-138) mg/dL, 141 (122-168) mg/dL and 92 (181-110) mg/dL, respectively. About 22% were on background LLT of whom 87% were on statins alone. Patients on LLT vs. no LLT were younger (median age 65 [Q1-Q3: 59-72] vs. 73 [66-80] years), had higher prevalence of tobacco users (29% vs. 17%) and high-risk DM (45% vs. 31%).

Conclusions:
In a large cohort of VESALIUS-CV like US patients, the majority had LDL-C sub-optimally managed with most not taking any LLT. This finding suggests an opportunity to reduce the treatment gap and improve lipid management in this population.
Abstract 4139087: An Interpretable Model for Predicting Preoperative Cardiorespiratory Fitness Using Wearable Data in Free-Living Conditions.
Authors: Hussain Iqram , Zeepvat Julianna , Reid Cary , Czaja Sara , Pryor Kane , Boyer Richard
Published: November 2024

Introduction:
Assessing preoperative cardiorespiratory fitness (CRF) is essential for determining surgical risk and outcomes. The advent of wrist-worn devices equipped with heart rate and activity monitoring presents new opportunities for CRF evaluation. Traditionally, CRF has been measured using submaximal exercise tests, such as the 6-minute walk test (6MWT). Monitoring CRF in everyday activities may offer valuable insights into patients' preoperative fitness levels. This study explores the potential of predicting 6MWT distances using a data-driven physiological CRF model derived from wearable devices in elderly patients in their free-living environments.

Hypothesis:
Machine-learning algorithms can accurately estimate CRF using data from fitness trackers.

Methods:
We examined heart rate and activity data from Fitbit devices worn by 65 older adult patients undergoing major noncardiac surgery. Data was collected over a week in free-living conditions. We aimed to utilize this wearable technology to forecast CRF in this group. A machine-learning ensemble regression model was employed to predict CRF, with 6MWT outcomes as the reference. The Shapley Feature Attribution method was applied to understand the contribution of specific features derived from wearable data to the model, aiding in personalized fitness predictions.

Results:
Higher CRF was associated with increased levels of moderate to vigorous physical activity (MVPA), maximal activity energy expenditure (aEEmax), 4-minute heart rate recovery (HRR), and non-linear heart rate variability (HRV) features. These measures positively correlated with improved 6MWT outcomes. Our regression models, including random forest and linear regression, showed strong predictive capabilities, with coefficients of determination (R^2) of 0.91 and 0.81, respectively. Shapley Feature Attribution analysis revealed that higher levels of MVPA, aEEmax, HRR240, and non-linear HRV dynamics are reliable indicators of better CRF test performance.

Conclusions:
Integrating wearable activity and heart rate data offers a robust framework for preoperative CRF assessment, enhancing surgical risk evaluation and patient outcomes in everyday conditions.
Abstract 4139234: Association of Social Determinants of Health (SDOH) with Incident Hypertension and Mediation by Epigenetic Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Szeto Mindy , Ning Hongyan , Pedamallu Havisha , Zheng Yinan , Schneper Lisa , Reges Orna , Hou Lifang , Allen Norrina , Notterman Daniel , Lloyd-Jones Donald
Published: November 2024

Background:
Social disadvantage, estimated by social determinants of health (SDOH) measures, is associated with subsequent incident hypertension (inc-HTN). We sought to determine whether associations between SDOH and inc-HTN may be mediated by epigenetic changes in DNA methylation represented by GrimAge acceleration (GrimAA).

Methods:
The CARDIA study enrolled 5,115 Black and white men and women participants (ppts) in 1985-1986. The current analysis focused on 3,067 participants with SDOH data and without HTN at CARDIA exam year 15 (Y15) in 2000-2001. Social disadvantage was defined by variables representing the 5 domains of SDOH: difficulty paying for basics, medications, or healthcare; food insecurity; census tract poverty; residential racial segregation; and parental education. GrimAA (a summary measure of DNA methylation) at Y15 was calculated as the difference between epigenetic age and chronological age. Inc-HTN was defined as blood pressure ≥140/90 or treatment after Y15. Age-, sex-, and race-adjusted Cox regression models assessed associations between each SDOH variable with inc-HTN prior to formal mediation analysis by GrimAA.

Results:
Study ppts had a mean age of 40y, 42.5% self-identified as Black, and 63.6% as female. Greater social disadvantage in every SDOH domain was associated with higher proportions of inc-HTN. Difficulty paying for basics or medications, the summed difficulty paying index, food insecurity, and parental education were each significantly associated with inc-HTN on adjusted Cox regression (Table). For example, those with food insecurity had a 34% higher hazard for inc-HTN (hazard ratio [HR] 1.34; 95% CI 1.12-1.60). Each level of parental education (e.g., completed college vs high school) was associated with 19% lower hazard for inc-HTN (HR 0.81, 95% CI 0.73-0.90). GrimAA mediated 14.6% of the food insecurity/inc-HTN association, and 34.9% of the parental education/inc-HTN association.

Conclusions:
Social disadvantage measures are associated with inc-HTN. DNAm measured by GrimAA appears to statistically mediate associations of SDOH with inc-HTN, suggesting potential molecular mechanisms by which SDOH may get “under the skin” to accelerate development of HTN over the life course.
Abstract 4139251: Right Atrial and Ventricular Strain Analysis in Patients with Carcinoid Heart Disease
Authors: Alabdaljabar Mohamad Saleh , Alexandrino Francisco , Al-Shakarchi Nader , Olgun Hilal , Lloyd James , Luis Sushil , Pislaru Sorin , Pellikka Patricia , Connolly Heidi
Published: November 2024

Background:
Carcinoid heart disease (CaHD) typically affects tricuspid and pulmonary valves and is associated with poor survival. To date, the role of right ventricular (RV) and atrial (RA) strain has not been evaluated in such cohort.

Research Questions:
To evaluate RV and RA strain patterns and assess their impact on survival and congestive heart failure (CHF) development.

Methods:
Retrospective study of CaHD patients (ICD 9/10 diagnosis of neuroendocrine tumor and echocardiographic evidence of CaHD prior to any surgical intervention; 2004-2019). Longitudinal strain was evaluated using speckle-tracking, RV/RA-focused view was used. RV strain was averaged from 3 and 6 segments for free wall (FWS) and global strain (GS), respectively. Auto-tracking with manual adjustment was done to ensure optimal tracking. The tracing of RV/RA endocardium was done with 15 points using the tricuspid valve annulus as a reference. The impact of strain parameters on mortality and CHF was evaluated with the Kaplan Meier and Cox proportional hazard analyses.

Results:
A total of 138 patients were included (mean age was 63 ± 10 years; 47% females). Median follow-up was 5.0 years (3.7-8.2). Significant RA and RV enlargement (72 and 79%, respectively) was more common than RV dysfunction (10%). The most common valvular disease
>
moderate was tricuspid regurgitation (TR; 97%) followed by pulmonary regurgitation (PR; 70%). RV GS mean was -21 + 6%, with FWS of -23 + 7%. The mean RA strain analysis revealed (93% sinus rhythm): a reservoir of 26 + 11%, a conduit of 14 + 8%, and an atrial contraction of 12 + 8%. Strain parameters were not associated with overall mortality. As opposed to PR/TR severity and RV/RA enlargement/dysfunction, patients with low RA reservoir strain (<23%) were more likely to develop CHF (adjusted-HR=1.80, p=0.04, 95% CI 1.04 - 3.134).

Conclusions:
Our findings suggests that CaHD patients have RV/RA dysfunction with overall reduced strain parameters. Patients with low RA reservoir had higher risk of CHF, but none of the RV/RA strain parameters were associated with excess mortality. This shows how strain analysis could complement other echocardiographic parameters in CaHD morbidity assessment.
Abstract 4139275: Degree of rurality moderates the association of sedentary behavior with cognitive function in patients with cardiac diseases
Authors: Lin Chin-Yen , Wu Jia-Rong , Cha Geunyeong , Biddle Martha , Chung Misook , Feltner Frances , Rayens Mary Kay , Moser Debra
Published: November 2024

Background:
Whether there are disparities in cognitive function in individuals living in rural areas compared to urban areas is unknown. Some investigators have found that rural residents have better cognitive function, while others report the opposite. Sedentary behavior is a major risk factor for cognitive health in patients with cardiac diseases; however, little is known about the impact of sedentary behavior on cognitive function at different degrees of rurality.

Purpose:
The aim of the study was to determine whether degree of rurality moderates the relationship between sedentary lifestyle and cognitive function among rural patients with coronary heart disease or heart failure.

Methods:
This study includes 135 coronary heart disease or heart failure patients residing in Appalachia (aged 59 ± 12 years, 53% female). Sedentary behavior was measured by the average daily sedentary time (in minutes) using accelerometry (ActiGraph). Cognitive function was assessed using the Montreal Cognitive Assessment-Blind. Rurality was determined by Rural-Urban Commuting Area (RUCA) codes. Participants were categorized into two groups based on degree of rurality: 1) 89 participants were included in a less rural group (RUCA codes 2−3 within Appalachia and RUCA codes 4−6 for micropolitan areas < 50,000 population); and 2) 46 participants were included in a more rural group (RUCA codes 7−10 for small towns < 9,999 population). Data were analyzed using the PROCESS macro in SPSS to test the proposed moderating effect controlling for age, gender, and depressive symptoms.

Results:
The time spent in sedentary behavior ranged from 3.2 to 13.3 hours per day, with an average of 7.9 ± 2.1 and a median of 7.8 hours per day. Sedentary behavior predicted cognitive function (B = −0.006, p = 0.012), but this relationship was moderated by rurality group (coefficient of rurality group*secondary behavior interaction term = 0.006, p = 0.029). Patients living in more rural areas had significantly worse cognitive function if they were sedentary for longer periods (p = 0.012), but this relationship was not observed in those living in less rural areas (p = 0.986).

Conclusions:
Although being sedentary is associated with worse cognitive function, degree of rurality significantly interacts with sedentary behavior in this association. Testing the impact of promoting physical activity on cognitive function is warranted in this population, particularly for those living in highly rural areas.
Abstract 4139301: Simultaneous Optogenetic Stimulation, Voltage, and Calcium Mapping of Human Engineered Cardiac Tissue
Authors: Guragain Bijay , Zhang Hanyu , Wu Yalin , Wang Yongyu , Wei Yuhua , Wood Garrett , Ye Lei , Walcott Gregory , Rogers Jack , Zhang Jianyi
Published: November 2024

Introduction:
Optogenetics can precisely stimulate cardiac tissue, while optical mapping of voltage (Vm) and calcium transients (CaT) can image electrophysiological function with high spatiotemporal resolution. Here, we present a novel method that combines optogenetic actuation with dual Vm/CaT optical mapping. The optogenetic channels and CaT indicator are genetically encoded, while the Vm indicator is an organic dye.

Methods:
For model tissue, we used cardiac spheroid (600-800 µm in diameter) comprising cardiomyocytes and cardiac fibroblasts that were differentiated from human induced pluripotent stem cells. We used lentivirus to express the optogenetic actuator CheRiff and the calcium reporter jRCaMP1b, and stained with a voltage dye, RH237. CheRiff was optically excited using royal blue LED light (450 nm), and both RH237 and jRCaMP1b were excited using a single green LED light source (560 nm) that excites both indicators. The two indicators emit in different bands; fluorescence was split with a dichroic mirror and directed to two cameras to image Vm and CaT simultaneously without crosstalk (Fig. A).

Results:
We first used electrical field stimulation to activate the spheroid while simultaneously imaging Vm and CaT. This demonstrated the efficacy of the recording system (Fig. B[I]). We then switched to optogenetic stimulation to demonstrate the all-optical system and acquired similar signals (Fig. B[II]).

Conclusions:
This relatively simple system enables all-optical actuation and readout of cardiac electrophysiology. The genetically encoded optogenetic actuator and CaT indicator can be expressed in engineered tissue, while the organic Vm indicator can be used to stain both wild-type tissue and engineered tissue. We expect the system to be useful to investigate electrical coupling between engineered tissue grafts and host tissue because it enables actuation and readout of engineered tissue to be unambiguously separated from host tissue.
Abstract 4139313: Prognostic Implication Of Fibrosis-4 Index for Risk Of Mortality In Chronic Heart Failure Patients With And Without Type 2 Diabetes.
Authors: Mohamed Abdullahi , Christensen Daniel , Schou Morten , Gislason Gunnar
Published: November 2024

Background and aim:
The Fibrosis-4 (FIB-4) score is recommended as a first-line screening tool to rule-out advanced liver fibrosis. It is highly recommended to screen for liver fibrosis in patients with Type 2 diabetes mellitus (T2DM) and elevated liver enzymes using the fibrosis-4 (FIB-4) score.However, this recommendation does not extend to patients with chronic heart failure (CHF) who do not have T2DM. We aimed to investigate the predictors of high risk for advanced liver fibrosis according to the FIB-4 score and its association with all-cause and cardiovascular mortality, as well as major adverse liver outcomes (MALO), in patients with CHF, both with and without T2DM.

Methods:
This was a nationwide registry-based cohort study. We included patients registered in the Danish Heart Failure Registry who had laboratory data available to calculate FIB-4 scores from April 2003 to December 2019. Patients were classified as low-risk (Fib-4 <1.3), indeterminate-risk (1.3 – 2.67), and high-risk of advanced liver fibrosis (≥2.67). The analysis was conducted using multiple logistic regression and Cox proportional hazards models.

Results:
A total of 6079 patients with CHF were included in the study. High-risk of advanced liver fibrosis was highly prevalent, affecting 30% of the studied population. Predictors of high-risk of advanced liver fibrosis, included older age, male sex, severe chronic kidney disease, previous myocardial infarction, ischemic heart disease, and atrial fibrillation/flutter. Patients in the high-risk group exhibited a significantly elevated risk of all-cause mortality (HR: 1.30, 95% CI: 1.17-1.45), cardiovascular mortality (HR: 1.80, 95% CI: 1.49-2.17), as well as MALO (HR: 4.42, 95% CI: 2.70-7.23) when compared to those in the low-risk group. This was regardless of the presence of T2DM. Additionally, patients in the indeterminate-risk group showed an increased risk of cardiovascular mortality (HR: 1.22, 95% CI: 1.02-1.46) and MALO (HR: 1.86, 95% CI: 1.13-3.06) when compared to the low-risk group.

Conclusion:
In this nationwide cohort study, we found a high prevalence of high-risk of advanced liver fibrosis according to the FIB-4 score. Several clinical predictors of high-risk of liver fibrosis was identified. High-risk patients exhibited significantly higher all-cause and cardiovascular mortality, as well as major adverse liver outcomes (MALO), compared to low-risk patients, independent of T2DM status.
Abstract 4139327: Life-Saving Synchrony: Treating Leadless Pacemaker-Induced Cardiogenic Shock with Cardiac Resynchronization Therapy
Authors: Mbisike Chinwe , Udongwo Ndausung , Lyonga Ngonge Anthony , Adeniyi Adeyinka , Esomonye Theodora , ALKUBEYSI MO , Zhuo David
Published: November 2024

Leadless pacemakers (LPMs) represent a significant advancement in cardiac pacing technology, offering several advantages over traditional transvenous systems. However, they are not without complications such as leadless pacemaker-induced cardiomyopathy (LPM-CMP). We present a case of cardiogenic shock from LPM-CMP requiring cardiac resynchronization therapy (CRT) as a rescue strategy.

A 77-year-old female with a history of heart failure with reduced ejection fraction, coronary artery disease status post recent percutaneous coronary intervention to the proximal-to-mid left anterior descending artery, complete heart block status post LPM implantation, and chronic kidney disease stage 3b, presented to the emergency department after a syncopal event. Initial vital signs were blood pressure 96/64 mmHg and heart rate 62 bpm, while LPM interrogation showed 100% right ventricular pacing burden. Physical exam revealed congestion with jugular venous distension and 2+ pitting bilateral lower extremity edema. Initial labs (BNP 4792 pg/mL, hs-troponin 202 ng/L, lactate 5.5 mmol/L, AST/ALT 68/30 U/L, and creatinine 3.3 mg/dL (baseline 1.5 mg/dL)) were consistent with SCAI Stage B cardiogenic shock. She was transferred to the cardiovascular intensive care unit for inotropic and vasopressor support. By hospital day 10, she was on 10 mcg/kg/min of dobutamine, 3 mcg/min of epinephrine, and 14 mcg/min of norepinephrine. Despite this and extensive diuresis, she continued to deteriorate. After ruling out acute coronary syndrome, LPM-CMP was suspected as the etiology, and CRT-D was implanted on day 14. Echocardiography-assessed stroke volume correspondingly improved from 25 mL on pressors to 30 mL after CRT-D and off pressors. She was subsequently optimized on heart failure guideline-directed medical therapy, and discharged home on day 19.

LPM-CMP is a rare but potentially serious complication of LPM implantation. Early recognition and appropriate management are essential for optimizing patient outcomes. In this case, CRT-D implantation proved to be a successful intervention, resulting in significant clinical improvement and symptom resolution. This underscores the importance of individualized patient management and the role of advanced device therapies in the treatment of LPM-induced complications. Further research is needed to better understand the risk factors, pathophysiology, and optimal management strategies for LPM-CMP, especially as a rescue strategy in cardiogenic shock.
Abstract 4139347: Clinical Outcomes of Endovascular versus Surgical Revascularization in Frail and Non-Frail Older Adults
Authors: Ko Darae , Park Chan Mi , Evans Peter , Pande Ashvin , Hamburg Naomi , Kim Dae Hyun
Published: November 2024

Background:
Recent clinical trials (BEST-CLI and BASIL-2) have produced divergent results comparing endovascular vs surgical therapy in chronic limb-threatening ischemia (CLTI). The difference may be related to varying levels of frailty among the patient included.

Objective:
To compare the risk of major adverse limb events (MALE) or death in endovascular vs surgical therapy in real-world older adults with and without frailty

Methods:
We applied target trial emulation framework. This retrospective study using the 2016-2022 Medicare data included patients aged ≥65 years with CLTI who underwent surgical or endovascular therapy without revascularization in the prior year. Frailty was defined as a claims-based frailty index ≥0.25. The primary outcome was a composite of MALE or death. After propensity score (PS) matching, we estimated hazard ratios (HRs) using the Cox proportional hazards model for the total population and by frailty levels.

Results:
Before PS matching, the endovascular group (n=37513) was older (78 vs 76 years), more likely to be women (43% vs 39%), dually eligible for Medicaid (35% vs 28%), frail (56% vs 40%), and more likely to have diabetes (79% vs 67%), chronic kidney disease (81% vs 68%) and prior stroke (32% vs 27%) compared to the surgical group (n=8754). After PS matching (n=8116 per group), surgical therapy was associated with a lower rate of the primary outcome in the total population (55 vs 77 per 100 person-years, HR 0.73, 95% CI 0.70-0.77). The benefit of surgical therapy was consistent in frail patients (71 vs 95 per 100 person-years, HR 0.76, 95% CI 0.71-0.81) and non-frail patients (45 vs 67 per 100 person-years, HR 0.68, 95% CI 0.64-0.73) (Figure). Mortality rates per 100 person-years for surgical and endovascular groups were 42 and 47, respectively, in frail patients and 17 and 22 in non-frail patients.

Conclusion:
The effect estimates from our real-world data study were consistent with the effect estimate from BEST-CLI trial, with no treatment effect heterogeneity by frailty levels. The rate of primary outcome was very high in the frail group with nearly half dying within one year after surgical or endovascular therapy.
Abstract 4139378: Paclitaxel-Coated Balloon Angioplasty vs. Uncoated Balloon Angioplasty in Patients with Coronary In-Stent Restenosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Curi David , Mariz Ferreira Passos Bárbara , Machado Viana Gomes Victor , Moraes Giovanna , Cunha Ana Beatriz Nepomuceno , de Sant Anna Melo Edielle
Published: November 2024

Introduction:
The potential benefits and risks of paclitaxel-coated balloon (PCB) angioplasty over uncoated balloon (UB) angioplasty in the management of coronary in-stent restenosis (ISR) is not well established.

Hypothesis/Aims:
This study aims to determine whether PCB angioplasty is superior to UB angioplasty in patients with coronary ISR in terms of target lesion revascularization (TLR), myocardial infarction (MI), and all-cause mortality rates.

Methods:
PubMed, Embase and Cochrane Central databases were systematically searched for randomized clinical trials (RCT) comparing PCB with UB angioplasty in patients with coronary ISR. Statistical analyses were performed using Review Manager version 5.4.1. Risk Ratios (RR) with 95% confidence intervals (CI) for dichotomous endpoints were computed with the use of a Mantel-Haenszel random effects model.

Results:
A total of 1,407 patients from 7 randomized clinical trials were included. Follow-up periods in the included studies ranged from 6 months to 1 year. PCB angioplasty significantly reduced TLR (RR 0.28; 95% CI 0.16-0.48; p<0.001) and MI (RR 0.57; 95% CI 0.36-0.92; p=0.02). However, there were no significant differences in all-cause mortality (RR 0.75; 95% CI 0.38-1.50; p=0.42).

Conclusion:
In the management of coronary ISR, PCB angioplasty reduced TLR and MI compared with UB angioplasty. Nevertheless, PCB did not have a significant impact on all-cause mortality in comparison with UB. Further studies with extended follow-up are necessary to determine long-term mortality effects.
Abstract 4139434: Promotion of cardiac fibrosis and heart failure by LMCD1
Authors: Gavali Joice Thomas , Qin Qing , Tongmuang Nopprarat , summer ross , Sun Jianxin
Published: November 2024

Introduction:
Cardiac fibrosis is a typical pathophysiological process associated with ECM deposition, resulting in tissue scaring and organ dysfunction. No specific antifibrotic therapies exist for cardiac fibrosis, mainly because of a limited understanding of disease mechanisms. The activated fibroblasts secrete numerous fibrotic factors and ECM components, thus contributing to the development and progression of cardiac fibrosis. LMCD1 (LIM and cysteine-rich domain) is a member of the LIM family of proteins, which is highly expressed in the heart, and its expression is markedly reduced in heart failure (HF) patients. The role of LMCD1 in cardiac fibrosis remains poorly understood. This study aims to define the role of LMCD in cardiac fibrosis and the molecular mechanisms involved.

Methods:
The expression of LMCD1 in cardiac myocytes and fibroblasts from adult mouse hearts was determined by western blot analysis. TGF-β1 was used to induce cardiac fibrotic responses
in vitro
in human cardiac fibroblasts. A loss-of-functional approach was used to determine the functional significance of LMCD1 in cardiac fibrosis. Global LMCD1 KO mice were utilized to determine the functional significance of LIMCD1 in cardiac fibrosis and remodeling
in vivo
using a murine model of angiotensin II (AngII)-induced fibrosis. Echocardiography was performed to measure the cardiac function.

Results:
LMCD1 is highly expressed in human CFs, and its expression is markedly upregulated in a time and dose-dependent manner in response to the treatment of TGF-β1. Furthermore, we found that LMCD1 expression was markedly increased in the heart in mice after 4 weeks of Ang II infusion. In human CFs, LMCD1 knockdown significantly prevented TGF-β1-induced expression of fibrotic genes, and LMCD1 KO mice are protected from developing cardiac fibrosis induced by Ang II infusion. Protein and mRNA levels of fibrotic genes were significantly reduced in the heart of LMCD1 KO mice compared to their WT controls. Ang II infusion significantly increased LVAW and LVPW in WT mice, which were markedly attenuated in LMCD1 KO mice. Mechanistically, we found that TGF-β1-induced phosphorylation levels of SMAD2/3 were substantially decreased in LMCD1-deficient CFs.

Conclusion:
Our findings identified LMCD1 as a critical regulator in promoting cardiac fibrosis by targeting TGF-β1/SMAD signaling and suggested that targeted inhibiting LMCD1 may represent a novel therapeutic strategy to ameliorate cardiac fibrosis.
Abstract 4139458: Trends and Disparities in Arrhythmia-Related Deaths among Older Adults in the United States, 1999-2020
Authors: Cheema Muhammad Rafay Shahzad , Nashwan Abdulqadir J.
Published: November 2024

Background:
Cardiac arrhythmias significantly contribute to mortality in the United States (US), especially among older adults. This study examines two decades of mortality data to identify patterns and disparities in arrhythmia-related deaths across various demographics and regions.

Hypothesis:
The study hypothesizes that there are discernible patterns and disparities in cardiac arrhythmia-related mortality rates based on factors such as sex, race/ethnicity, and geographic region. It also seeks to determine whether these mortality rates have changed significantly over the past two decades.

Aims:
The objective is to identify patterns and disparities in cardiac arrhythmia-related mortality rates in the US older population over the past two decades

Methods:
Data were obtained from the CDC WONDER (1999-2020) focusing on arrhythmia-related deaths identified by ICD-10 codes I47, I48 and I49. The study examined demographic and regional patterns of mortality, employing statistical techniques for analysis. Joinpoint regression analysis was utilized alongside calculations of age-standardized mortality rates (ASMR) per 10,000 population and annual percentage change (APC). These metrics were stratified by year, sex, race/ethnicity, and geographic region to assess and compare variations in mortality trends over time

Results:
From 1999 to 2020, 3,516,612 arrhythmia-related deaths occurred in the US. ASMR per 10,000 increased from 38.0 in 1999 to 47.0 in 2020. Mortality rates decreased from 1999 to 2009 (APC: -0.9; 95% CI: -1.8, -0.4, p = 0.007), increased from 2009 to 2018 (APC: 1.5; 95% CI: 0.4, 2.3, p = 0.021), and significantly rose from 2018 to 2020 (APC: 7.4; 95% CI: 3.5, 9.4, p < 0.001). Men accounted for 45.8% of deaths, with an ASMR of 45.2 compared to 33.0 for women. Non-Hispanic (NH) Whites had the highest ASMRs (40.5), followed by NH Blacks (31.1), NH American Indians (28.3), Hispanics (22.7), and NH Asians (19.7). The Midwest had the highest ASMRs (41.2), followed by the West (38.8), South (36.4), and Northeast (36.3). Nonmetropolitan areas had higher ASMRs (42.1) compared to metropolitan areas (37.2)

Conclusions:
After initially declining from 1999 to 2009, arrhythmia-related mortality have increased thereafter with evident disparities. Highest ASMRs were found in NH White and male populations, and in the Midwest and nonmetropolitan regions. These findings underscore the need for targeted interventions to reduce such mortality, particularly among vulnerable groups
Abstract 4139469: Efficacy of Post-Procedure Voltage Mapping (PPVM) Guided Incremental Ablation Lesions in Improving 1-Year Success and Recurrence-Free Survival for Atrial Fibrillation Ablation
Authors: Vemulapalli Hema Srikanth , Rodriguez-Riascos Juan , Iyengar Sumedh , Iyengar Shruti , Muthu Padmapriya , Srivathsan Komandoor
Published: November 2024

Introduction:
Pulmonary Vein Isolation (PVI) has become the cornerstone during ablation of Atrial Fibrillation. The primary goal of the procedure is to prevent potential arrhythmogenic triggers from accessing the main left atrial substrate. However, incomplete fibrosis leading to PV reconnection has been identified as the primary reason for AF recurrence. It is unclear whether immediate voltage mapping and additional lesions delivered to areas of residual or recovered voltages will improve the outcome. This study evaluates the 1-year success and long-term recurrence-free survival in patients who underwent post-procedure voltage mapping (PPVM) to identify residual Low-Voltage Areas (LVAs) to guide the delivery of additional ablation lesions.

Methods:
We analyzed 588 patients who underwent PVI from 2015 to 2023. Of these, 243 had PPVM done to determine LVAs and guide additional ablation lesions. The control arm comprised 345 patients who underwent PVI by the same operators without PPVM. The primary endpoints were 1-year success and longer-term recurrence-free survival. Secondary endpoints were the incidence of complications and the prevalence of LVAs in patients who underwent PPVM.

Results:
Patients who underwent remapping were older than the control arm (68.3 vs 65.6 years, p = 0.005). There were no other significant differences in baseline characteristics between the two groups. At 1-year follow-up, the success rates were 79% in the treatment arm compared to 72% in the control arm (p = 0.038). Patients in the intervention arm had a recurrence-free survival rate of 65% and 54% at 2 and 4 years, respectively, compared to 62% and 43% in the control arm (p = 0.044). The prevalence of LVAs in the treatment arm was 56.8%. Additionally, complication rates were not increased in the remapping arm (3% vs 8%, p = 0.012).

Conclusion:
PPVM-guided incremental ablation lesions improve the 1-year success rate and recurrence-free survival at 2 and 4 years compared to traditional PVI without increasing complications due to additional lesion delivery.
Abstract 4139472: Increased Arachidonic Acid Eicosanoids in African Americans with Heart Failure with Preserved Ejection Fraction
Authors: XKhatib-ShahidiX XBellaX , Aradhyula Vaishnavi , Fares Anas , Dube Prabhatchandra , Sherafati Alborz , Kloster Alex , Khuder Sadik , Haller Steven , Kennedy David , Gupta Rajesh , Khouri Samer
Published: November 2024

Background:
African Americans demonstrate increased prevalence, earlier onset, and worse prognosis of heart failure with preserved ejection fraction (HFpEF) compared to non-African Americans. Recent studies have implicated circulating, bioactive lipids such as eicosanoids in mediating systemic inflammation. Eicosanoids may play a role in HFpEF pathogenesis. In addition, prior studies have identified arachidonic acid (AA) gene variants in African Americans that predispose to elevated circulating AA eicosanoid levels.

Objective:
We sought to analyze the differences in eicosanoid levels between African American and non-African American patients with HFpEF.

Methods:
Venous and arterial blood samples were collected during right heart catheterization from 22 African American and 68 non-African American patients with HFpEF. AA lipids were analyzed using liquid chromatography-mass spectrometry. Statistical analysis was performed using Student’s unpaired T-test and Chi-squared analysis.

Results:
African American patients demonstrated higher venous anti-inflammatory prostaglandin E1 (PGE1) (p<0.0001), prostaglandin E2 (PGE2) (p=0.0002), pro-inflammatory thromboxane B3 (TXB3) (p=0.0152), pro-inflammatory 20-hydroxyeicosatetraenoic acid (20-HETE) (p<0.0001), anti-inflammatory 14,15-epoxyeicosatrienoic acid (14,15-DiHETrE) (p=0.0005), and pro-resolutory lipoxin A4 (LXA4) (p<0.0001). Similarly, African American patients had elevated arterial 20-HETE (p=0.0029) and LXA4 (p=0.0421).

Conclusion:
This study demonstrates significant differences in levels of venous and arterial eicosanoids between African Americans and non-African Americans with HFpEF.
Abstract 4139484: Electrophysiologic Characteristics, Outcomes and Potential Predictors of Acute Success After Ventricular Tachycardia Ablation in Patients with Cardiac Sarcoidosis: Systematic Literature Review and Meta-Analysis
Authors: Rodriguez-Riascos Juan , Vemulapalli Hema Srikanth , Muthu Padmapriya , Iyengar Shruti , CHAUDHARY RAJVI GAJENDRA , Srivathsan Komandoor
Published: November 2024

Background:
Cardiac sarcoidosis (CS) is a rare condition marked by conduction disturbances, and ventricular tachycardia (VT) resulting from reentrant pathways. VT ablation is typically considered for patients with refractory VT. This systematic review aims to synthesize reported outcomes and identify potential predictors for the success of VT ablation in CS patients.

Methods:
A systematic literature review was conducted following the PRISMA guidelines, searching PubMed, Cochrane, Embase, and Scopus databases up to May 2024. A random-effects model was used to evaluate electrophysiologic and procedural variables and compare outcomes to identify potential predictors of success.

Results:
After excluding duplicates, 473 titles and abstracts were screened. Twenty-five studies were fully reviewed, and 9 studies comprising data from 311 CS patients who underwent VT ablation were included. The mean age of patients was 50.5 years, with 30% being female. Epicardial mapping was performed in 29% (CI 22-36%; 72/251) of cases, and 96% (CI 77-100%; 65/72) of those underwent epicardial ablation. The prevalence of VT storm before the procedure was 28% (CI 16-42%; 89/259), with a suppression success rate of 84% (CI 73-93%; 64/76). The acute complete success rate defined as lack of inducibility was 58% (CI 49-66%; 174/307). During follow-up, which ranged from 19 to 58 months, 34% (CI 21-48%; 113/271) of patients survived free from the composite outcome of death, transplantation, or VT recurrence. Patients with acute success had fewer inducible VTs (MD –1.1; CI: -1.8 to -0.5; p < 0.001). No other variables were significantly associated with acute success. However, patients with acute success tended to be older than those with partial or unsuccessful outcomes (MD 7.5; CI: -0.2 to 15.1; p = 0.055).

Conclusion:
VT ablation in patients with CS shows acceptable acute success rates. Patients presenting with VT storm have a high rate of arrhythmia acute suppression. A lower number of inducible VTs is associated with higher acute success rates. Despite these results, the prognosis remains poor, with a significant proportion of patients experiencing disease recurrence, death, or requiring heart transplantation.