bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140427: Potassium-sparing Diuresis and Natriuresis With a Novel Renal Outer Medullary Potassium Channel Inhibitor, in Healthy Adult Participants
Authors: Soleman Sharif , Schumacher Justin , Wang Beqing , Maya Juan , Levesque Paul , Mohammad Atif , Christopher Lisa , Sivakumar Pitchumani , Kozinn marc , Wang Chang , Ma Johnny , Bui Anh , Rao Veena , Testani Jeffrey , Ramirez-Valle Francisco , Murthy Bindu , Merali Samira , Baribaud Frederic , Costet Philippe
Published: November 2024

Introduction:
Persistent congestion and edema remain an unmet need in heart failure (HF). BMS-986308, a novel inhibitor of the Renal Outer Medullary Potassium Channel (ROMK), is predicted to enhance potassium-sparring diuresis and natriuresis in HF patients with persistent congestion and edema despite SOC treatment. We present pharmacodynamics and biomarkers of kidney function and injury from a first-in-human study of BMS-986308 (NCT04763226).

Method:
Thirty-two adult healthy participants were assigned to 1 of 4 dose cohorts (3, 10, 30, and 100 mg) and randomized (6:2) to receive a single dose of BMS-986308 oral solution or matching placebo. Diuresis and natriuresis were measured in intervals over 24 h post dose and baseline-adjusted using matching intervals at Day -1. Serum creatinine, cystatin C, electrolytes (K, Ca, Cl, Mg), aldosterone, renin activity; and urinary protein and albumin to creatinine ratios (UPCR, APCR); and biomarkers of kidney injury Kim1, NAGASE, OPN, CLUST were measured up to Day 5. Statistical significance between BMS-986308 treatment groups and placebo was assessed using unpaired
t
tests. Results are mean (±SD). ** P<0.01, *** P<0.001

Results:
BMS-986308 increased natriuresis and diuresis in a dose-dependent manner starting at the 30 mg dose. The table below presents change from baseline (CFB). No significant change in kaliuresis was observed (mean placebo and 100mg dose respectively 0.08 ± 0.03 and 0.05 ± 0.01 mmol/min over 24h). Aldosterone and renin activity peaked at 24h at 30 mg and 100 mg (CFB 132 ± 102% and 405 ± 129%***, 121 ± 130% and 783 ± 282%** respectively). A transient rapid dose-dependent increase in serum creatinine was observed at the 100 mg dose (CFB 44 ± 12% at 6h***, 28 ± 13% at Day2***, 11 ± 9% at Day4**, 100 mg dose) as well as a less pronounced increase in serum cystatin C (peak at 30 ± 6% at 12h***, 100 mg dose). No meaningful change was observed for the other biomarkers tested.

Conclusion:
BMS-986308 significantly increased diuresis and natriuresis in healthy participants while sparing potassium. In line with the substantial natriuresis, activation of the RAAS pathway and transient elevations of serum creatinine and cystatin C (with no change in kidney injury markers) was observed.
Abstract 4140472: Promotores De Salud: An Essential Workforce in Enhancing Hypertension Health Knowledge in Puerto Rico
Authors: Patel Janak , Arowolo Mide , Cosme Pitre Carmen , Scanlin Kathleen , Vargas Alizenet , Wagner Ashley , Sanchez Eduardo
Published: November 2024

Introduction:
Hypertension (HTN) is a major risk factor for cardiovascular disease, and its prevention and management are influenced by health knowledge. This paper reviews the findings of a community-based HTN health knowledge program in Puerto Rico, facilitated by Community Health Workers (CHWs), also known as Promotores de Salud, who maintain a close relationship with their communities.

Hypothesis:
CHWs will positively impact a community’s HTN health knowledge and self-reported confidence in making lifestyle/behavior modifications with the use of Empowered to Serve (ETS) Health modules.

Methods:
American Heart Association (AHA) partnered with One Stop Career Center, a community-based organization in Puerto Rico. The program utilized AHA ETS modules focused on HTN prevention and management. CHWs instructed and implemented these modules across 10 community-based settings from 09/20/23 to 12/26/23. Participants were given a multiple-choice survey before and after each module. Descriptive Analysis and Two Proportion Z Test was performed on the surveys.

CHWs also conducted a community discussion, distributed blood pressure devices, and referred participants to a self-measured blood pressure program.

Results:
The total count for pre-surveys was 214 and post-surveys was 224. Majority of participants identified as female (67.9% female) and Hispanic (95.2%), with 46.4% completed high school or less.

Comparing pre- and post-surveys, confidence scores improved in monitoring blood pressure at home (41.0%, n/N=34/83 to 68.5%, n/N=61/89; p value=<0.001) , lifestyle changes to manage blood pressure (35.4%, n/N=29/82 to 73.0%, n/N=65/89; p value=<0.001), reading a nutrition label (40.2%, n/N=51/127 to 69.9%, n/N=95/136; p value=< 0.001), using spice alternatives when cooking (60.6%, n/N=77/127 to 80.7%, n/N=109/135; p value=<0.001), and reducing processed foods (36.5%, n/N=46/126 to 68.4%, n/N=93/136; p value=<0.001).

Graph 1 contains the results of 4 knowledge-based questions.

Conclusions:
The data suggest that the CHWs, with the use of ETS modules, might play an important role in enhancing HTN health knowledge and improving confidence to support lifestyle/behavior modifications within Puerto Rican communities.
Abstract 4140489: COMPARE CABG: A Meta-Analysis of Comparative Outcomes in On-Pump vs. Off-Pump Coronary Artery Bypass Grafting.
Authors: da Nóbrega Borges José Victor , Machado Manuella , Leila Samira
Published: November 2024

Background:
Coronary artery bypass grafting (CABG) can be performed using on-pump or off-pump techniques. The optimal approach remains debated. Objectives: The COMPARE CABG (Comparative Outcomes of Mortality, Perioperative complications, cARdiac function, and Hospital stay in On-Pump versus Off-Pump Coronary Artery Bypass Grafting) study aims to systematically compare the outcomes of these surgical approaches.

Methods:
A comprehensive search was conducted in Pubmed, Cochrane Library, and other databases. Studies with a sample size > 4000 were included. Outcomes analyzed included mortality, complications, cardiac function, and hospital stay.

Results:
Meta-analysis of 5 studies with 58,232 patients showed that off-pump CABG was associated with a slightly lower complication rate: 15% for on-pump CABG and 13.5% for off-pump CABG with a pooled effect size of 0.90 (95% CI: 0.85-0.95). In terms of cardiac function and hospital stay, results were also favorable to off-pump CABG with an effect size of 1.12 (95% CI: 1.05-1.19) and 1.15 (95% CI: 1.10-1.20), respectively. The pooled mortality rate was 2.5% for on-pump and 2.4% for off-pump CABG, with an effect size of 1.05 (95% CI: 0.98-1.12), indicating no significant difference between the groups.

Conclusion:
These findings suggest that off-pump CABG may be a preferable option for reducing surgical complications, though both techniques yield comparable mortality outcomes. Further research is needed to explore long-term cardiac function and patient-specific factors influencing the choice of surgical method.
Abstract 4140504: Effect Of Resmetirom On Lipid Panel: Meta-Analysis Of Randomized Controlled Trials
Authors: Kommu Sharath , Sharma Param , Shah Milind , Alaoua Mohammad , Soodi Deepa , Berg Richard
Published: November 2024

Background:
Resmetirom is useful in improving liver parameters in patients with nonalcoholic steatohepatitis (NASH) or metabolic dysfunction-associated steatohepatitis (MASH). However, its beneficial effects on lipid panel parameters are unclear.

Methods:
We searched PubMed and ClinicalTrials.gov using the search term resmetirom. Among the studies identified, we looked for randomized-controlled trials with information on resmetirom and lipid panel. We identified four studies which compared resmetirom 80 mg to placebo, and performed a meta-analysis. A random effects model was utilized when heterogeneity was detected (p-value for heterogeneity<0.1)

Results:
Our study shows that resmetirom, significantly improved lipid parameters of low-density lipoprotein cholesterol (LDL-C) (mean difference [MD] -13.01, 95% confidence interval (CI) -15.38 to -10.64, p<0.0001), triglycerides (MD -30.61, 95% CI -48.30 to -12.93, p=0.0007), apolipoprotein B (MD -18.78, 95% CI -24.90 to -12.66, p<0.0001), lipoprotein (a) (MD -24.89, 95% CI -38.67 to -11.11, p=0.0004). There was an improvement in high-density lipoprotein cholesterol (HDL-C), but it was not statistically significant (MD 1.32 95% CI -0.49 to 3.14, p=0.15).

Conclusion:
Resmetirom, used to treat NASH (or MASH), can significantly improve lipid panel parameters, potentially offering cardiovascular benefits. To fully understand its impact on cardiovascular health, large-scale randomized controlled trials focusing on cardiovascular outcomes are necessary.
Abstract 4140511: Synergistic insulinotropic and lipolytic actions of GLP-1 and a novel miniaturized designer GC-A peptide activator in Beta cells and adipocytes: Potential therapeutic insights for cardiometabolic disease
Authors: Zheng Ye , Pan Shuchong , Moroni Dante , Chen Horng , Sangaralingham Jeson , Burnett John
Published: November 2024

BACKGROUND:
Atrial natriuretic peptide (ANP) and glucagon-like peptide-1 (GLP-1) are endogenous hormones known for roles in cardiovascular regulation and metabolic homeostasis. ANP mediates its actions via the GC-A receptor, while GLP-1 via the GLP-1 receptor (GLP-1R). Both peptides may stimulate insulin secretion from pancreatic beta cells and augment lipid metabolism in adipocytes, yet potential synergistic effects remain unexplored. To optimize ANP activation of GC-A, we developed a novel 15 amino acid miniaturized GC-A activating peptide CRRL555. CRRL555 possesses greater GC-A binding and activating properties than ANP.

AIMS:
We investigated the metabolic properties of CRRL555/GC-A and its interaction with GLP-1/GLP-1R in vitro.

METHODS:
Rat pancreatic beta cells (INS-1) were stimulated with high glucose (20mM) and treated with GLP-1 or CRRL555 (10
-10
-10
-6
M) and together for 1 hr. Supernatant was collected and insulin was measured by ELISA. Human visceral adipocytes were differentiated for 10 days and then treated with GLP-1 or CRRL555 (10
-10
-10
-6
M) or together for 6 hrs. Supernatant was collected and glycerol and free fatty acid (NEFA), indicators of lipolysis, were measured.

RESULTS:
CRRL555 (p<0.05) and GLP-1 (p<0.05), dose dependently, stimulated insulin secretion in INS-1 cells in the presence of high glucose. Importantly, CRRL555 combined with GLP-1, resulted in a greater enhancement (p<0.05) of insulin secretion compared to either peptide alone. While high dose CRRL555 and GLP-1 (10
-6
M) stimulated lipolysis in visceral adipocytes with increases in glycerol and NEFA, only CRRL555 at low dose (10
-10
M), and not low dose GLP-1 (10
-10
M), stimulated glycerol and NEFA production (p<0.05). When low dose GLP-1 (10
-10
M) was added to low dose CRRL555(10
-10
M), lipolysis was like CRRL555 alone.

CONCLUSION:
We report a novel synergy in insulin release from beta cells with combined stimulation of the potent and miniaturized GC-A designer peptide CRRL555 with GLP-1. CRRL555 possesses greater lipolytic properties compared to GLP-1 in visceral adipocytes at low doses advancing novel metabolic actions of CRRL555 alone or combined with GLP-1R activation. These in vitro studies of dual receptor activation of GC-A and GLP-1R highlight the therapeutic potential of combining CRRL555 with GLP-1-based therapies for the treatment of cardiometabolic diseases, thus supporting studies of dual GC-A/GLP-1R activation in experimental cardiometabolic disease states.
Abstract 4140515: Children’s Heartbeat: Improving Global Knowledge and Care of Pediatric Arrhythmias
Authors: Gakenheimer-Smith Lindsey , Etheridge Susan , Batra Anjan , Sanatani Shubhayan , Holiman Hannah , Nahey Tara , Balaji Seshadri
Published: November 2024

Background:
Expertise in pediatric electrophysiology (PEP) is lacking in most low- and middle- income countries (LMIC), yet arrhythmias are a ubiquitous and common pediatric clinical problem. Strategies to disseminate PEP education are essential to improve patient care. Children’s Heartbeat (CHB) is a video-conferencing program using the Extension for Community Healthcare Outcomes (ECHO
TM
) model to disseminate PEP knowledge to clinicians in LMIC. The impact of CHB in disseminating PEP is unknown.

Objective:
We evaluated the impact of CHB in improving clinicians’ confidence in PEP.

Methods:
Since CHB inception in December 2020, monthly cross-sectional surveys of CHB participants, including longitudinal evaluation of participants’ confidence caring for PEP patients, were performed using a 5-point Likert scale, with 1 being low-confidence and 5 high-confidence. Average session participation and post-session evaluations were used as indicators of viewer engagement.

Results:
CHB currently has 181 registrants from 31 countries, with 53% working in an LMIC (Figure 1). Participants include nurses, medical students, physician assistants, general cardiologists, and pediatric and adult electrophysiologists. Only 30% have PEP training; 53% do not have access to PEP consultation in their workplace. Average session participation was 64, with an additional 121 viewing recorded sessions posted after the live program. On average, participants’ confidence in PEP increased from 2.8 before to 4.0 after CHB sessions (Figure 2).

Conclusions:
CHB successfully disseminates PEP knowledge to LMIC globally and increases clinicians’ confidence in PEP conditions. Future directions include increasing viewership by pediatric cardiology trainees and pediatric cardiologists in rural regions in high-income countries, partnering with international pediatric and cardiology groups to expand program outreach, and evaluating the direct impact of CHB on patient care in LMIC.
Abstract 4140535: High throughput screen reveals that atypical antipsychotics promote continual efferocytosis by antagonizing dopamine signaling and promoting vitamin A-dependent Arginase1 upregulation
Authors: Kojima Yoko , Ye Zhongde , Wang Fudi , lotfi Mozhgan , Adkar Shaunak , Bell Caitlin , Luo Lingfeng , Fu Changhao , Leeper Nick
Published: November 2024

Introduction:
Programmed cell removal, or efferocytosis, has been proposed as a method to dispose of unwanted cells that accumulate to promote diseases such as cancer, infection, and atherosclerosis. The defective efferocytosis process in advanced atherosclerotic plaque causes secondary necrosis and contributes to plaque vulnerability. Blockade of ‘don’t eat me’ molecules such as CD47 induces favorable vascular effects, but can induce the clearance of some healthy tissue such as RBCs. Accordingly, we conducted a high-throughput screen of about 3000 FDA-approved drugs and compounds, to identify new pro-efferocytic therapies that may have translational potential.

Methods&Results:
Using flow cytometry-based phagocytosis assays with RAW 264.7 murine macrophages, we identified 8 candidate compounds that reproducibly increased efferocytosis. Subsequent validation assays using Incucyte live-cell imaging assay in RAW cells, primary cultured murine macrophages, and human macrophages allowed us to identify the atypical antipsychotic drug, thiothixene, as a promising candidate for clinical translation, which induced cellular clearance without changing macrophage apoptosis, migration or proliferation. Leveraging thiothixene’s known inhibitory effects on a wide range of neurotransmitters and catecholamines, we found that dopamine has a potent inhibitory effect on efferocytosis, which thiothixene could partially offset. Thiothixene induced macrophage polarization and Arginase1 upregulation, promoting continual efferocytosis. Mechanistically, RNA-sequencing revealed that thiothixene upregulated Stra6L, a receptor for retinol-binding protein that mediates cellular uptake of retinol. Retinol and all-trans retinoic acid upregulated Arginase1 expression and promoted efferocytosis, which could be reversed via knockdown of Stra6l.

Conclusion:
This unbiased screen identified unanticipated anti-efferocytic properties of dopamine, while highlighting the translational potential of a generic, FDA-approved anti-psychotic drug. This therapy may represent a novel method for promoting continual efferocytosis and the disposal of unwanted cells that otherwise can promote a range of clinical disorders including atherosclerosis.
Abstract 4140544: Right ventricular free wall strain is superior to other methods of measuring right ventricular systolic function following invasive treatment for acute pulmonary embolism
Authors: Nguyen Cathy , Paliwoda Ethan , Wang Denny , Mustafa Ahmad , Villarrubia Varela Lourdes , Mehla Priti , Thampi Shankar , Kodra Arber , Roselli Victoria , Kattih Zein , Mina Bushra , Kliger Chad , Goldberg Ythan
Published: November 2024

Introduction:
Treatment for acute pulmonary embolism (APE) includes both noninvasive and invasive strategies. Transthoracic echocardiography (TTE) is the predominant test to assess right ventricular (RV) function following function, which is associated with adverse clinical outcomes. However, specific methods to measure RV function in clinical practice vary and have not been well-studied in the setting of APE. We sought to determine whether invasive treatment for APE was more effective than noninvasive treatment at achieving normal RV function as determined by various TTE measures.

Methods:
Data for 108 individuals treated for APE at our institution were retrospectively reviewed. All post-treatment TTE were performed within 72 hours of admission and prior to hospital discharge. There were no in-hospital mortalities. Logistic regression analysis was used to identify independent predictors of normal RV function defined as TTE-measured right ventricular-to-left ventricular diameter (RV/LV) ratio ≥ 0.9, tricuspid annular plane systolic excursion (TAPSE) ≥ 17.0mm, fractional area change (FAC) ≥ 35.0%, and right ventricular free wall strain (RVFWS) ≤ -20.0%. Independent variables chosen for analysis were: patient age, initial heart rate, syncope on presentation, presence of saddle PE on computed tomography, and having received invasive treatment for APE (catheter-directed thrombolysis, catheter-directed thrombectomy, or surgical thrombectomy).

Results:
Mean age was 61.5 (±17.7) years and 50.0% were male. Mean heart rate on presentation was 101 (±18) per minute. 16.7% presented with syncope and 23.1% were diagnosed with saddle. 55 (50.9%) patients were treated invasively, of whom 15 received catheter-directed thrombolysis, 36 mechanical thrombectomy, and 4 surgical thrombectomy. RV function data were as follows: RV/LV ratio = 0.95(±0.22), TAPSE = 18.9(±5.4) mm, FAC = 32.4(±4.4) %, RVFWS = -18.9 (±4.6) %. Invasive treatment was an independent predictor of normal RVFWS (p=0.04, odds ratio 2.6, 95%CI 1.1 - 6.8), but not of other measures of RV function. No other variables independently predicted any of the measures of normal RV function.

Conclusion:
An invasive treatment strategy for APE is more effective than a noninvasive strategy in achieving normal RV function as measured by RVFWS. Other measures were not associated with APE treatment type, suggesting that RVFWS should be the method of choice to assess RV function.
Abstract 4140630: Serum Metabolites Predict Mortality or Transplant in Pre-capillary and Combined Pre- and Post-capillary Pulmonary Hypertension in the PVDOMICS Cohort
Authors: Dreier Matthew , Chung Samuel , Racanelli Alexandra , Chacon-Barahona Jonathan , Horn Evelyn
Published: November 2024

Introduction:
Efforts to stratify mortality risk in pulmonary hypertension (PH) have focused on the minority of patients in WSPH group 1. Metabolomic studies in group 1 identify histidine, polyamines, tRNA metabolites, and homoarginine as predictors of mortality. Little is known about the role of metabolomics to predict mortality in the larger group of PH patients.

Question:
Which serum metabolites predict a composite of mortality or transplant in pre-capillary, post-capillary, and combined pre- and post-capillary PH (Cpc-PH), irrespective of WSPH group?

Aims:
To identify predictive metabolites in the Pulmonary Vascular Disease Phenomics Program (PVDOMICS) cohort and understand the pathobiology relating predictors to mortality/transplant.

Methods:
We generated peripheral venous metabolomic data in 649 PH subjects. We defined pre-capillary PH as pulmonary vascular resistance (PVR)>2 WU and pulmonary capillary wedge pressure (PCWP)≤15 mmHg (n = 453), post-capillary PH as PVR≤2 WU and PCWP>15 mmHg (n=25), and Cpc-PH as PVR>2 WU and PCWP>15 mmHg (n = 171). We used Cox models with multiple testing correction to identify predictive metabolites in each group. We then correlated select predictors with hemodynamic, laboratory, and echocardiographic data.

Results:
The hemodynamic groups included a mix of WSPH groups. We identified 249 predictors in pre-capillary PH, 0 in post-capillary PH, and 7 in Cpc-PH. Homoarginine predicts mortality/transplant in pre-capillary PH (HR=0.56, p<0.001) and Cpc-PH (HR=0.59, p=0.025). In pre-capillary PH, low homoarginine is associated with high PVR (r=-0.26, p<0.001), high BNP (r=-0.49, p<0.001), RV dilation (p<0.001 for moderately dilated, p<0.001 for severely dilated vs. normal), and RV free wall longitudinal strain (r=-0.31, p<0.001).

Conclusions:
Many metabolites predict mortality/transplant in pre-capillary PH and Cpc-PH, including those previously identified in group 1 as well as newly identified predictors. To our knowledge, this is the first report of such predictors in hemodynamic subsets rather than in WSPH groups. Our data suggest low homoarginine contributes to increased PVR, RV failure, and mortality/transplant in pre-capillary PH. More studies on homoarginine are needed.
Abstract 4140636: Mapping Ventricular Arrhythmogenic Substrates: Insights from Electroanatomic and Cardiac Magnetic Resonance in Ischemic and Non-Ischemic Cardiomyopathies
Authors: Casper Morgan , Bernstein Hannah , Rosen Sasha , Borgardt Soren , McCann Alexandra , Ghasemiesfe Ahmadreza , Srivatsa Uma
Published: November 2024

Background:
Electroanatomic mapping (EAM) and cardiac magnetic resonance (CMR) identify substrates using parameters from ischemic cardiomyopathy (ICM). CMR's application to characterize scar in non-ischemic dilated cardiomyopathy (NIDCM) is limited.

Objective:
To assess scar burden and patterns in patients with VA and NIDCM or ICM and the concordance between CMR and EAM.

Methods:
We reviewed 27 patients with VA ablations (NIDCM and ICM) and prior CMR. ARVC, HCM and infiltrative diseases were excluded. Scar type and morphology were classified (table 2). Myocardial late gadolinium enhancement (LGE) (> 2SD or 3SD) and T1 values were compared to remote myocardium. EAM defined bipolar scar <1.5 mV and unipolar scar <8.3 mV. Scar locations were assigned using the AHA 17-segment model. Cohen’s Kappa coefficient was used to assess categorical agreement of scar severity between CMR and EAM (table 4).

Results:
Scar distribution in NIDCM was predominant in the mid-myocardial septum and ICM in the sub-endocardium (p <0.001). ICM patients had higher presence of posteromedial papillary muscle scar (p=0.001). The difference in myocardial T1 values at the mid-chamber and mid-septum was not significant, likely influenced by the mid-LV chamber short axis cut. The right ventricle was dilated with reduced function and non-compacted myocardium was thicker in NIDCM. Bipolar scar was predominant in AHA segments 1-3 and 9-10 for NIDCM patients and AHA segments 3-12 in ICM patients. AHA segments 4 and 8-12 had fair correlation between bipolar EAM and CMR. Unipolar mapping showed slight agreement in segments 1-6, 9, 11, 13, 15 and 16.

Conclusions:
Scar is predominant in the mid-myocardial septum in NIDCM compared to subendocardial location in ICM. Comparing CMR, EAM at best correlate fairly to midventricular segments in bipolar map slightly to most segments in unipolar map. Improved mapping tools will likely improve ablation success.
Abstract 4140638: CARDIAC TUMORS EVOLUTION IN PATIENTS WITH TUBEROUS SCLEROSIS
Authors: Hotta Viviane , Ribeiro Anna Christina , Quadro Matos Maria Rosa , Tanaka Ana Cristina , Soliani Marilia , Oishi Gardenia , Rocha Ruiza , Miura Nana , Fernandes Fabio
Published: November 2024

Background:
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by the formation of benign tumors located mainly in the central nervous system, skin, kidneys, heart, eyes and lungs . It is estimated that 70% to 90% of rhabdomyomas (the most prevalent cardiac tumors in the pediatric population) are related to TSC. Most cardiac tumors regress spontaneously during the first year of life. However, there are reports of recurrence, suggesting the possibility of hormonal influence.

Purpose:
To perform a descriptive study of clinical variables, with a cardiological focus, electrocardiographic, echocardiographic and cardiac magnetic resonance imaging characteristics, in addition to the treatment and clinical evolution of patients diagnosed with TSC treated over 24 years of follow-up.

Methods:
A retrospective, descriptive study will be carried out at the Clinical Unit of Cardiomyopathies and Congenital Heart Diseases of InCor/FMUSP. Data was collected from the institution's electronic medical record from January 1997 to January 2021. Patients with a clinical and or genetic diagnosis of TSC were selected. Analysis of clinical, electrocardiographic, echocardiographic and CMR variables were performed. Death and the need for surgical treatment will also be evaluated. Data from the first and last TTE and CMR available in the system were analyzed.

Results:
77 patients with TSC diagnosis were included, 47 (61%) patients were females. The mean age of the patients was 24 ± 15.1 years. The majority of patients (N = 67; 87%) self-reported white ethnicity. 50 patients had cardiac tumors, 49 patients had rhabdomyomas (RM) and 1 patient presented with pericardial lipoma. Between the patients with RM, 15 (30%) had single tumors and 35 (70%) patients had two or more tumors. Regarding clinical evolution, 39 patients (78%) presented incomplete involution, 9 patients (18%) complete regression and 1 patient presented an increase in the mass. Surgical treatment was necessary, at some point, in 4 (8%) patients and 2 (4%) patients died during the postoperative period. There is no record of heart transplantation.

Conclusions:
Regarding clinical variables, 64% of the patients had cardiac tumors. Most patients were asymptomatic, only (4%) had complex ventricular arrhythmias. Most patients had multiple LV or biventricular rhabdomyomas assessed by TTE or CMR. The majority of patients (78%) had incomplete involution of rhabdomyomas in 24 years of follow-up.
Abstract 4140649: A Simple One-Item Nursing Falls Assessment Predicts Outcomes For Patients With Stage D Heart Failure Undergoing Surgical Advanced Therapies
Authors: Salvador Vincent , Perez Jaime Abraham , Hudec Paige , Gorodeski Eiran , Oneill Thomas
Published: November 2024

Introduction:
Frailty portends worse outcomes for patients with advanced heart failure (HF) undergoing surgical advanced therapies. Falls are characteristic of frailty, but it is unknown to what degree a history of falls predicts post-operative risk. We hypothesized that a one-item falls survey routinely conducted by nurses in ambulatory settings is associated with worse outcomes in this population.

Methods:
We conducted a retrospective cohort study of all patients undergoing heart transplantation or left ventricular assist device (LVAD) implantation at our institution between January 2020 and December 2023. Our primary exposure of interest was falls as assessed by a nursing questionnaire (“Have you had one or more falls within the last year?”) within 12 months or less prior to surgery. We investigated a variety of relevant clinical outcomes including hospital- and ICU-length of stay, duration of mechanical ventilator use, renal replacement therapy, and survival.

Results:
The cohort consisted of 73 primarily middle-aged (median age 55 y) white (53%) men (75%), of whom 10 (14%) had a history of falls. Compared to those without falls, those with a history of falls had a higher prevalence of albuminemia (28% vs. 60%, P=0.043) and lower peak VO2 (11.3 ml/kg/min vs. 6.9 ml/kg/min, P=0.015). History of falls was associated with increased time on mechanical support (mean difference: +1.5 days, P=0.002), prolonged ICU stay (mean difference: +13 days, P=0.03), and prolonged hospital stay (mean difference: +17 days, P=0.03). Patients with a history of falls also had a higher rate of needing renal replacement therapy in the 90-days following surgery (adjusted HR 4.7, 95% CI 1.1-20, P=0.035). There were no differences in survival between the two groups.

Conclusions:
Among patients with advanced HF undergoing heart transplantation or LVAD, a simple one-item nursing falls assessment is associated with markers of malnutrition and poor cardiovascular performance, and predicts clinically-relevant worse outcomes.
Abstract 4140656: Educational Attainment Level and Risk of Mortality and Cardiopulmonary Outcomes in High-Risk Cardiovascular Disease Patients: The INVESTED Trial
Authors: Lassen Mats , Howell Nicholas , Claggett Brian , Biering-Srensen Tor , Vardeny Orly , Solomon Scott , Udell Jacob , Joseph Jacob , Hegde Sheila
Published: November 2024

Background:
Social determinants, such as educational attainment level (EAL), are indicators of socioeconomic status and have been shown to be inversely related with adverse health outcomes. However, the association between EAL and risk of cardio-pulmonary events in heart failure (HF) and myocardial infarction (MI) survivors has not been extensively investigated.

Methods:
In the INVESTED trial, 5260 patients from the US and Canada with recent HF or MI hospitalization were randomized 1:1 to high-dose trivalent or standard-dose quadrivalent influenza vaccine from Sep 2016 to Jan 2019. We examined the association between EAL and risk of adverse clinical outcomes for each participant across all enrolling seasons using Cox models adjusted for treatment assignment and clinically relevant confounders and stratified by trial entry year. Participants were categorized by EAL (high school or less [HS], post-high school or trade [post-HS/T], and college or more [Col+]).

Results:
Of the 4,912 participants (mean age: 65.5 years, 28% females, 80% White, 39% with MI and 61% with HF hospitalization as qualifying event) with EAL information, 43% were in the HS group, 28% were in the post-HS/T group, and 29% were in the Col+ group. At baseline, those with higher EAL were more likely to be White or Asian, be married/with long-term partner, have higher left ventricular ejection fraction, have lower NYHA class, and less likely to have cardiovascular comorbidities and risk factors than those with lower EAL. During follow-up (median: 9 months [6-16]), 1,706 (35%) participants experienced the composite of all-cause death or cardiopulmonary hospitalization. Compared to HS, higher EAL was associated with a stepwise decrease in the risk of the composite outcome (post-HS/T: HR: 0.88 95%CI: [0.79-0.99]; Col+: HR: 0.71 95%CI: [0.63-0.81], overall p-value <0.001). A similar protective effect of higher EAL was observed for additional adverse clinical outcomes (
Figure
).

Conclusion:
High EAL is independently associated with a decreased risk of adverse clinical outcomes in patients with high-risk cardiovascular disease, highlighting the need to consider EAL in risk assessment and target additional resources towards those with low EAL to improve prognosis.
Abstract 4140664: From Atrial Fibrillation to Rare Genetic Disorder: The Unexpected Diagnosis of Birt-Hogg-Dubé Syndrome
Authors: Casper Morgan , Bernstein Hannah , Srivatsa Uma
Published: November 2024

Introduction:
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant disorder due to mutations in the FLCN gene. As an AMPK-mTOR interacting molecule, this loss-of-function mutation impacts energy homeostasis leading to uninhibited cell growth. While studies have linked this genetic mutation to severe cardiac hypertrophy, a connection to persistent atrial fibrillation (AF) is unestablished. We present a case in which an individual's initial symptoms of AF ultimately led to a diagnosis of BHDS.

Case Summary:
A 56-year-old male with a history of “holiday heart syndrome” presented for an AF consultation. Despite alcohol cessation, he continued to have paroxysmal AF with severe fatigue and palpitations. After three unsuccessful cardioversions and refractory episodes despite Dronedarone therapy, he was scheduled for an ablation. A pre-procedural transesophageal echocardiogram showed a left ventricular (LV) ejection fraction of 55%, mild concentric LV hypertrophy, and mild left atrial enlargement. These enlargements were new compared with imaging one year prior. A cardiac gated CT detailed the pulmonary vein structure and incidentally revealed bilateral cystic lung changes, leading to a pulmonology referral. Despite an initial successful ablation targeting the pulmonary vein, his symptoms returned within days. He was loaded with amiodarone. Monitoring on his apple watch showed a high burden of AF. He underwent a repeat ablation to achieve complete pulmonary vein isolation with improvement in his symptoms. Further pulmonary evaluation highlighted a family history of spontaneous pneumothorax and a dermatology consultation then confirmed BHDS via fibrofolliculoma biopsy.

Discussion:
This case underscores the importance of comprehensive evaluations, revealing a rare genetic disorder from an initial AF assessment. While no definitive link exists between BHDS and cardiomyopathy, we aim to understand possible connections between this rare condition and its systemic cardiovascular impacts. We propose that upregulation of mTORC1 activity and attenuation of AMPK from the loss of function of FLCN lead to uncontrolled cell division and left ventricular hypertrophy. This hypertrophy then results in left atrial dilation, contributing to the development and persistence of AF. Given the rarity of this condition, more research is needed on symptom onset and systemic linkages. Swift diagnosis from incidental findings are crucial for managing symptoms and the underlying disease.
Abstract 4140677: Racial disparities in acute type B aortic dissection presentation, management, and outcomes: insights from the International Registry of Acute Aortic Dissection (IRAD)
Authors: Patel Priya , Evans Cole , Harris Kevin , Taylor Bradley , Li Qing-Guo , Isselbacher Eric , Sultan Ibrahim , Bhan Anil , Gilon Dan , Coselli Joseph , Glotzer Owen , pai Chih Wen , Brinkman William , Brinster Derek , Eagle Kim , Schermerhorn Marc
Published: November 2024

Background:
Racial disparities are known to exist in cardiovascular disease such as acute coronary syndrome and heart failure. However, data are limited in examining possible racial disparities related to aortic dissection due to the rare nature of this disease.

Hypothesis:
We hypothesize that, among patients presenting with acute type B aortic dissection, racial differences exist in disease severity at time of presentation as well as initial management, in-hospital and long-term outcomes.

Methods:
Our analysis included white (n = 2517, 80%) and black (n = 629, 20%) patients with acute Type B aortic dissection in the International Registry of Acute Aortic Dissection collected from 62 sites between 1996 and 2024. Other races were excluded given small sample size and limited follow up data.

Results:
When compared with white patients, black patients were younger (mean age 58 ± 12 years vs 65 ± 14 years, P < .0001), and more likely to have a history of hypertension (94% vs 83%, P < .0001), diabetes (19% vs 11%, P < .0001), chronic kidney disease (18% vs 9.5%, P < .0001), and cocaine use (14% vs 1.6%, P < .0001). Black patients were also more likely to present with abdominal pain (51% vs 43%, P = .003), lower extremity pain (16% vs 11%, P = .018), hypertension (72% vs 61%, P < .0001), renal malperfusion (24% vs 12%, P < .0001), abdominal vessel involvement (58% vs 47%, P < .0001) and pericardial effusion (12% vs 6%, P = .001). Black patients were more likely to undergo endovascular management (40% vs 28%, P < .0001) and less likely to be medically managed alone (49% vs 61%, P < .0001). Prior to any intervention, black patients were more likely to experience stroke (3.3% vs 1.1%, P = .001) and extension of dissection (10% vs 7.2%, P = .028). In-hospital mortality was similar (black 6.5% vs white 8.4%, P = .139). Overall survival was also similar at 4 years post-discharge (black 86% vs white 83%, P = .172). Among patients with endovascular management, black patients had better 4-year survival (93% vs 81%, P = .028).

Conclusions:
Our analysis shows differences in baseline characteristics, presentation, management, and in-hospital adverse events for black patients presenting with acute type B dissection compared to white patients; however, without any significant difference in in-hospital or 4 year mortality. Future studies may aim to evaluate modifiable risk factors and optimal treatment strategies to reduce the incidence of aortic dissection in black patients.
Abstract 4140682: Clinical Case: Flipping the Script: Tackling CAD in Dextrocardia During Cardiac Catheterization
Authors: Riya FNU , Iqbal Naveed
Published: November 2024

Introduction:
Dextrocardia is a rare congenital condition where the heart's apex points to the right, with an incidence of about 0.01%. Patients usually have a normal life expectancy unless other structural heart diseases are present. The prevalence of atherosclerotic coronary artery disease (CAD) in these individuals is believed to be similar to that of the general population.

Due to its rarity, data on coronary interventions in this subset are scarce, with available literature mostly limited to case reports. Patients with dextrocardia present a diagnostic challenge, particularly in the context of acute coronary syndrome.

Case Presentation:
A 49-year-old male with a medical history of dextrocardia, hypothyroidism, dyslipidemia and hypertension was referred to a cardiologist by his primary physician due to a 3-week history of unstable angina. His vital signs were normal, and the physical examination was unremarkable. Electrocardiogram (ECG) showed a prominent S wave in the left-sided leads and a prominent R wave in the right-sided chest leads, suggesting dextrocardia. Although he had a normal echocardiogram and stress test a year ago at a different hospital, due to his symptoms and intermediate-high risk probability of coronary artery disease (CAD), the decision was made to proceed with a cardiac catheterization using a trans-radial approach with a horizontal sweep technique. During the procedure, a 6-French tiger catheter (TIG) was guided into the left coronary sinus and advanced into the left ventricle under fluoroscopic guidance.

The left main coronary artery was widely patent bifurcating into the left anterior descending and left circumflex. The left circumflex had 80% proximal stenosis with minimal luminal irregularities in the mid to distal portion. After guidewire crossing, balloon angioplasty was performed, and a drug-eluting stent was deployed. An intravascular ultrasound was also performed, which was negative for vessel dissection. There were no post-procedure complications, and the patient was discharged on beta blockers and dual antiplatelet agents.

Conclusion:
Performing cardiac catheterization in patients with dextrocardia presents unique technical challenges due to the mirror-image anatomy. This case report highlights the modifications in standard techniques, emphasizing the need for specialized skills and strategies to achieve successful outcomes in such cases.
Abstract 4140690: Management of Ventricular Septal Defect after Bipolar Radiofrequency Ablation for Ventricular Tachycardia
Authors: Gupta Manasvi , Silverstein Joshua , Oehler Andrew , Shaw George
Published: November 2024

Background:
Ventricular septal defect (VSD) can develop as a rare complication in patients undergoing bipolar radiofrequency ablation for ventricular tachycardia (VT).

Case:
A 67-year-old male with nonischemic cardiomyopathy underwent three VT ablations over 2 years for recurrent LV summit VT. At the initial procedure, minimal bipolar voltage abnormality but significant unipolar voltage abnormality was found at the basal interventricular septum, periaortic tissue, and left ventricular (LV) summit, consistent with mid-myocardial fibrosis. Extensive endocardial unipolar radiofrequency ablation (RFA) was performed on the LV side. Despite lack of inducibility with triple extrastimuli, VT recurred that was treated with sotalol and mexiletine.

One year ago, due to recurrent symptomatic VT, he underwent a redo ablation. The clinical VT mapped earliest to the right ventricular (RV) side of basal anteroseptum. Extensive RV and LV endocardial unipolar RFA was performed, but VT remained inducible. Therefore, ethanol ablation was performed through septal perforating branch of the distal coronary sinus, after which VT could not be induced. A month later, he returned in VT storm. Repeat study mapped clinical VT earliest to the basal anteroseptal RVOT, with a focal breakout pattern on both LV and RV consistent with a deep septal substrate (earliest activation signals ~40 ms preQRS). After attempting unipolar ablation from the LV aspect, bipolar ablation was performed across the basal anterior interventricular septum. VT could no longer be induced with triple extrastimuli, on isoproterenol.

On recent routine outpatient visit 6 months later, a new murmur was noted. Multimodality imaging revealed a large (10 mm) outlet VSD in the anteroseptum with left to right shunt (Qp:Qs 1.5). LV function and cardiac index were mildly reduced (CI 2.0 ml/kg/m
2
). No evidence of pulmonary hypertension or RV dysfunction. After multidisciplinary heart team discussion, decision was made to attempt surgical closure.

Conclusion:
Patients with refractory VT managed with multiple ablations at the same focus using different technologies should be closely monitored on an outpatient basis to evaluate for rare complications such as VSD.
Abstract 4140702: Sex Differences Revealed by Single Cell Transcriptome Analysis of Peripheral Blood Mononuclear Cells in Single Ventricle/Hypoplastic Left Heart Patients
Authors: Qu Huiqi , Ostberg Kayleigh , Slater Diana , Wang Fengxiang , Snyder James , Hou Cuiping , Connolly John , March Michael , Glessner Joseph , Kao Charlly , Hakonarson Hakon
Published: November 2024

Background:
Single ventricle (SV) and hypoplastic left heart syndrome (HLHS) present significant sex differences in terms of surgical outcomes and long-term prognosis between male and female patients. Peripheral blood mononuclear cells (PBMCs) drive tissue damage and cardiac dysfunction, contributing to the sex-specific clinical outcomes.

Aims:
We used single-cell RNA sequencing (scRNA-seq) to assess gene expression profiles in PBMCs, aiming to gain insights into sex effects and identify new biomarkers for assessing disease prognosis.

Methods:
We studied PBMCs from 32 cases with SV/HLHS. The experiments were conducted in 3 independent batches (9 females/11 males; 2 females/6 males; 2 females/2 males), using 10X Chromium Single Cell Gene Expression assay (10x Genomics, Single Cell 3' v3). Sequencing was performed using the Illumina NovaSeq6000. The data analysis was conducted using the Seurat R package, employing SCTransform for data normalizing and scaling (Satija, Farrell et al. 2015, Butler, Hoffman et al. 2018). To mitigate batch effects, the 3 batches were analyzed separately.

Results:
42 genes were consistently identified of differential expression (DE) (|log
2
FC|≥0.25,
P
adj<0.05) in each of the 3 batches, including 38 upregulated (6 on ChrX) and 4 downregulated genes in females. Notably, 3 autosome genes were also identified of DE in SV/HLHS cases compared to controls:
PPP1R15A
upregulated in cases has lower expression in females;
EVL
and
CLEC2D
downregulated in cases have higher expression in females. The expression of these 3 genes is more significant in naïve CD4
+
T cells, CD14
+
Monocytes, NK cells, and naïve B cells.

Conclusion:
PPP1R15A
mediates cellular stress responses and apoptosis (Blais, Filipenko et al. 2004).
EVL
negatively regulates cell migration (Lambrechts, Kwiatkowski et al. 2000).
CLEC2D
mediates immune sensing of cell death through the recognition of histone sequences (Lai, Cruz et al. 2020). The expression changes in females may mitigate inflammation and immune dysregulation in SV/HLHS patients. The significance of these genes as prognostic markers and potential targets for therapeutic intervention in SV/HLHS management warrants further research.
Abstract 4140708: Association between Age at Menopause and Age at Onset of Myocardial Infarction: An Analysis of NHANES Data from 2017-2020
Authors: Kulthamrongsri Narathorn , Suriyathumrongkul Napat , Wanichwecharungruang Nisha , Nuchpramool Prachawanee , Kulthamrongsri Kritpong , Siramongkholkarn Smuch , KOOKANOK Chutawat , Yinadsawaphan Thanaboon , Wattanachayakul Phuuwadith , Saowapa Sakditad , Danpanichkul Pojsakorn , Ongsupankul Sorawit , Sripusanapan Adivitch , Wareesawetsuwan Nicha , Lorlowhakarn Koravich , Deepan Natee , Mohpichai Nopavit , Siritongtaworn Phatsawut , Tantisattamo Ekamol
Published: November 2024

Introduction:
Menopause is known to be associated with myocardial infarction (MI). However, the association between menopause age and MI onset in a nationally representative population remains unknown.

Objective:
To examine the correlation between age of menopause and age of MI onset in the general population and the association between early menopause (onset of menopause ≤ 40 years old) and early onset of MI (onset of MI ≤ 40 years old).

Methods:
A cross-sectional study was conducted using a population from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The questionnaire collected self-reported data on the participants' menopause age and their age of first MI. The relationship between these two parameters was analyzed by multivariate linear and logistic regression analyses. Multivariate analysis was adjusted for race, age, body mass index (BMI), smoking status, diabetes mellitus (DM), hypertension, and dyslipidemia status.

Results:
Among 2,200 postmenopausal females, 90 (4.1%) have had MI. The study involved 85 postmenopausal females who reported both menopause age and MI onset, with a mean ± SD age of 55 ± 13 years. This study found a significant association between menopause age and MI onset. After adjusting for confounders, it was found that every 1-year increase in the age of menopause will delay the onset of MI by 0.28 years, with a 95% CI of 0.013 to 0.552 (Table 1A, Graph 1A, Graph 1B).

Additionally, early menopause carries an almost significantly increased risk of 2.11 times (95% CI: 1.00, 4.45) for early-onset MI. After adjusting for confounders, the magnitude of the association was lower and not statistically significant, but the direction remains (OR (95% CI): 2.08 (0.87, 4.95)). However, after stratification with comorbidities, DM status was identified as an effect modifier, with early MI significantly observed in patients with DM in both univariate and multivariate analyses, with OR (95% CI) of 3.03 (1.10, 8.37) and 4.88 (1.26, 18.96), respectively (Table 2A).

Conclusion:
This study demonstrated a positive association between menopause age and MI onset in a generally representative population. This suggests that prolonged estrogen exposure due to late menopause may delay the onset of MI. Additionally, early menopause was associated with early MI onset in the DM population. Further longitudinal studies are required to examine the potential mechanisms involved in menopause onset and MI onset.