bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146507: Sex-Based Disparities in Atrial Flutter Outcomes: An Analysis of the National Readmission Database
Authors: Arcidiacono Anne Marie , Klei Lauren , Hapshy Vera , Arcidiacono James , Imburgio Steven , Patel Swapnil , Hossain Mohammad , Heaton Joseph
Published: November 2024

Background:
Atrial flutter (AFL) is a common supraventricular tachyarrhythmia characterized by a rapid and regular atrial rate. Although the global burden of atrial flutter on the general population has risen dramatically over the past four decades, the impact of sex on clinical outcomes for these patients is poorly characterized. This study aims to investigate sex disparities in clinical outcomes over recent years for patients admitted with atrial flutter.

Methods:
In this large scale, retrospective cohort study, adult patients who were admitted with AFL were analyzed from 2016 to 2021 using the National Readmissions Database. The study population was divided into male and female groups. Diagnoses were classified using the International Classification of Diseases, 10th edition codes. The primary outcome was 30-day readmissions. Secondary outcomes included inpatient mortality and length of stay.

Results:
A total of 132,027 patients with AFL meeting inclusion criteria were included in the study. Of these, 82,988 (62.9%) were male and 49,040 (37.1%) were female. The mean age was 63.0 ± 11.5 for males vs 67.2 ± 11.4 years for females. Readmissions were higher in females (10% vs 9%) than males. Cox regression analysis showed higher readmission events in females (HR: 1.07, 95% CI: 1.01-1.13, p < 0.010) when compared to males. Multivariate regression analysis for inpatient mortality and length of stay was higher for females than males (p < 0.01 for both).

Conclusion:
Women experienced higher readmission rates and had worse outcomes including inpatient mortality and higher length of stay compared to their male counterparts. These findings suggest that female patients may require closer monitoring and targeted intervention to improve these outcomes.
Abstract 4146509: L-Lactic Acid Reduces Infarct Size After Ischemia In Isolated Mouse Hearts Through Acidosis, MCT1-Mediated Uptake, And Metabolic Reprogramming
Authors: Cler Marina , Perez-Amodio Soledad , Valls-Lacalle Laura , Martinez Elena , Barba Ignasi , Ganse Gino Freddy Sena , Engel Elisabeth , Rodriguez-Sinovas Antonio
Published: November 2024

Introduction:
Lactic acid is increasingly recognized as an alternative fuel source for various tissues, including the brain and heart. It is acknowledged as a protective compound in tissues such as the brain, particularly under conditions like traumatic brain injury or ischemia-reperfusion. However, its potential as a cardioprotective agent remains controversial.

Aims:
We aimed to (1) evaluate the impact of acute L-lactic acid administration at reperfusion onset on myocardial infarct size in isolated mouse hearts after transient global ischemia, and (2) elucidate the underlying mechanisms.

Methods:
Isolated mouse hearts underwent 35 min global ischaemia followed by 60 min of reperfusion and were randomly assigned to experimental groups. Control hearts (n=7) received standard Krebs buffer, while L-lactic acid-treated hearts received Krebs containing 8 or 20 mmol/L L-lactic acid for the first 15 minutes of reperfusion (n=5). To assess the contribution of acidosis to the observed effects, 5 hearts were treated with acidic Krebs (pH 7.0) for the same time period. To evaluate the role of import of L-lactic acid through monocarboxylate transporter 1 (MCT1) in those effects, additional hearts (n=6) were treated with L-lactic acid and 1 μmol/L AR-C141990 hydrochloride.

Results:
L-lactic acid induced a concentration-dependent reduction in infarct size, achieving a 23% reduction at 20 mmol/L (from 44.74±2.24 to 21.46±1.93%, ANOVA and Tukey’s tests, p=0.0006). This protective effect was associated with reduced lactate dehydrogenase release and improved functional recovery during reperfusion. Perfusion with an acidic Krebs also reduced infarct size, but to a lesser extent than L-lactic acid (see Figure). MCT1 inhibition with AR-C 141990 attenuated the protective effect of L-lactic acid to the levels seen with the acidic Krebs (see Figure).
1
H NMR spectroscopy revealed significant metabolic changes in L-lactic acid-treated hearts, with pathway enrichment analysis indicating nearly a 3-fold enrichment in pyruvate metabolism, fatty acid biosynthesis, and gluconeogenesis, suggestive of a metabolic shift.

Conclusions:
These findings support a cardioprotective role for L-lactic acid against ischemia-reperfusion injury, attributable to both acidosis and MCT1-mediated uptake, leading to metabolic reprogramming.
Abstract 4146512: Modifiability of Post-Exercise Oxygen Uptake Recovery Patterns: A Substudy of the SEQUOIA-HCM Randomized Trial
Authors: Newlands Chloe , Griskowitz Catharine , Campain Joseph , McGinnis Shaina , Giverts Ilya , Moreno Fabely , Landsteiner Isabela , Claggett Brian , Coats Caroline , Kulac Ian , Lee Matthew , maron Martin , Olivotto Iacopo , Owens Anjali , Jacoby Daniel , Heitner Stephen , Kupfer Stuart , Malik Fady , Meng Lixin , Wohltman Amy , Malhotra Rajeev , Lewis Gregory
Published: November 2024

Background:
Recent heart failure studies show that post-exercise VO
2
recovery (VO
2
Rec) patterns track closely with exercise cardiac output and outcomes, but not with peripheral oxygen (O
2
) extraction. In patients with obstructive hypertrophic cardiomyopathy (oHCM), studies of VO
2
Rec changes with effective cardio-specific interventions are lacking. We hypothesized that treatment with aficamten, a next-in-class cardiac myosin inhibitor, would shorten VO
2
Rec in patients with oHCM.

Methods:
SEQUOIA-HCM is the pivotal phase 3 trial of aficamten in symptomatic patients with oHCM (New York Heart Association functional class [NYHA FC] II-III, peak VO
2
[pVO
2
] ≤90% predicted, respiratory exchange ratio ≥1.05). Patients were randomized 1:1 to aficamten or placebo for 24 weeks with the primary endpoint of change from baseline (BL) in pVO
2
. For this analysis, VO
2
Rec was measured as the time taken after exercise cessation for VO
2
to decline by 12.5% (t
12.5%
), 25%, or 50% of pVO
2
. Response rates for achieving clinically meaningful threshold reductions (>15 seconds) in t
12.5%
, and correlations with changes in cardiac function (echocardiographic parameters/cardiac biomarkers) were assessed.

Results:
Among 282 randomized patients (mean age 59.1±12.9 years, 115 female [41%]), 263 (93%) had CPETs at BL and W24 with VO
2
Rec values as shown (
Table
). At W24, t
12.5%
improved by 8sec (95% CI, -12, -5sec, p<0.001) in the aficamten group compared to the placebo group. Those treated with aficamten were more likely to improve t
12.5%
by ≥15sec (OR 3.7 95% CI 1.9-6.9, NNT=4.8) than those on placebo. Shortening of t
12.5%
correlated with reduced NT-proBNP, high-sensitivity cardiac troponin I, left ventricular outflow tract gradient, and improved NYHA FC and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (all p<0.005).

Conclusion:
This is the first study to establish that VO
2
Rec is modifiable in response to cardio-specific intervention (aficamten) in patients with oHCM. VO
2
Rec (t
12.5%
) shortened proportionally and in parallel with other metrics of improved cardiac function, underscoring the benefits of aficamten for oHCM, and supporting inclusion of VO
2
Rec as a routine metric for evaluating cardio-specific interventions for oHCM.
Abstract 4146535: Prevalence and In-hospital Outcomes of Cardiac events in Women with underlying Infertility Condition:A National Inpatient Database Analysis
Authors: Sanka Sujana , Hotwani Priya , Nanavaty Dhairya , Sinha Rishav , Chigurupati Himaja Dutt , Neppala Sivaram , Basit Jawad , Alraies M Chadi
Published: November 2024

Introduction:
Cardiovascular(CV) disease is one of the leading cause of death in females in USA out of which 44% suffer. According to the latest CDC guidelines, 13.4 % are suffering from the infertility.It includes the most common conditions including endometriosis, poly cystic ovarian syndrome. Studies shows a mutlitude of factors including genetic abnormalities, hormonal imbalances like chronic anovulation or increased androgens predispose the women to subsequent health conditions.Literature review suggests that long term cv risks are less understood in the infertile women.

Aim:
The aim of the study is to identify the CV outcomes including coronary heart disease(CAD) , acute coronary syndrome(ACS), and heart failure in women with underlying infertility condition.

Methods:
The NIS 2020 was queried for the female adult population (age>18 years) with a primary or secondary diagnosis of infertility. Prevalence of CV risk factors were compared between females with and without infertility problem. The association of cardiac diagnoses including CAD, ACS and was analysed. Multivariate regression analysis was performed taking all-cause mortality as a primary outcome.

Results:
A total of 3870 adult patients with a primary or secondary diagnosis of infertility were identified and the mean age was 36 years.In adult population without infertility condition, patients with an underlying infertility were found to have an increased association with DM (48.16%vs 23.11%; P<0.001),HLD(56.14% vs 30.72%; P<0.001),hypothyroid(17.47% vs 10.47%; P<0.001),metabolic syndrome(0.23% vs 0.16%; P<0.001) while we found decreased association in tobacco abuse( 14.18% vs 17.12%; P<0.001),HTN(1.47% vs 37.95%; P<0.001). The prevalence of CAD(46.64% vs 12.59%; P<0.001), ACS(46.64% vs 12.59%; P<0.001) was also found to be significantly higher in women with infertility. In the female subpopulation with infertility, approximately 5.91% of patients died. However, the odds of mortality was significantly increased if patients had underlying ACS (OR- 2.77; C.I.-2.72 -2.87; P<0.001) or CAD (OR- 3.97; C.I.: -3.93-4.02; p<0.001). There was no statistically significant increased mortality with HF( OR:1).

Conclusion:
In our study, infertility in women was associated with higher prevalence of CAD and ACS. The odds of mortality also increased if women with infertility condition if they developed ACS or CAD. Further clinical research and studies are warranted to understand its CV outcomes.
Abstract 4146563: Physician follow up and cardiac testing after a first diagnosis with secondary vs. primary atrial fibrillation in-hospital
Authors: Mohammed Basma , Fang Jiming , Dorian Paul , Lee Douglas , Ha Andrew , Jackevicius Cynthia , Ko Dennis , Austin Peter , Singh Sheldon , Abdel-Qadir Husam
Published: November 2024

Background:
Secondary atrial fibrillation (AF) is triggered by acute illness and associated with adverse outcomes. Timely follow-up is recommended by the American Heart Association statement on acute AF.

Hypotheses:
Patients with secondary AF receive less follow-up and cardiac testing than those primarily hospitalized for AF (primary AF).

Follow-up is lower for secondary AF patients hospitalized for noncardiac diagnoses.

Methods:
Population-based cohort study using linked administrative datasets of patients aged ≥66 yrs discharged alive after a new diagnosis of AF while hospitalized in Ontario between Apr 2013 - Mar 2019. Patients were classified as secondary or primary AF using a validated approach based on discharge diagnosis type and followed for 1yr. Outcomes included physician visits (family physicians [FP], internists, cardiologists), and cardiac testing (electrocardiograms [ECG], echocardiograms, ambulatory ECG monitoring). The cumulative incidence function was used to quantify the incidence of outcomes. Cause-specific hazards regression was used to estimate hazard ratios (HR) associated with hospitalization type in secondary AF patients. Regression analyses accounted for competing risks.

Results:
We studied 13,011 secondary AF (35.2% cardiac surgery, 9.6% cardiac medical, 17% noncardiac surgery, 38.1% noncardiac medical) and 11,065 primary AF patients. Secondary AF was associated with lower age, male sex, less heart failure, and greater prevalence of other comorbidities. Less than 50% of secondary AF patients had visits to internists, cardiologists, echocardiograms or ambulatory ECG monitoring (see Figure). The incidence of all outcomes was significantly lower for secondary than primary AF. Among secondary AF patients, specialist follow-up and cardiac testing rates were lowest after noncardiac diagnoses (see Table).

Conclusion:
Patients with secondary AF have less specialist follow-up and cardiac testing than primary AF, especially if hospitalized for noncardiac diagnoses.
Abstract 4146605: A Non-odorant Olfactory Receptor Ligand Depolymerizes the Platelet Actin Cytoskeleton to Prevent Thrombosis
Authors: Aggarwal Anu , Wang Nancy , Josyula Vara Prasad , Yang Moua , Young Shim , Kennedy Quinn , Samuel Reina , Sangwan Naseer , Guntupalli Suman , Godwin Matthew , Ali MAriya , Jennings Courtney , Rajasekar Bhairavi , Scalise Alliefair , Stauffer Shaun , McCrae Keith , McIntyre Thomas , Cameron Scott
Published: November 2024

Background:
Despite antiplatelet therapy use, some patients have residual thrombotic risks due to High residual platelet reactivity (HRPR). We identified ectopic expression of Olfactory Receptor (OR) 2L13, a G protein-coupled receptor, in human platelets that suppresses platelet reactivity when activated. Our goal was to identify agonists in a high throughput screen for OR2L13 as an alternative strategy to suppress HRPR.

Methods:
Using an OR2L13 reporter cell line, 8K bioactive compounds were screened. Lead compounds were validated, and orthogonally tested for antiplatelet effects by Light Transmission Aggregometry (LTA) and Flow cytometry. Using murine models, the impact of OR2L13 agonists was determined by evaluating thrombosis and hemostasis. Lastly, the impact of a lead OR2L13 agonist on HRPR in patients with coronary artery disease (CAD) and peripheral artery disease (PAD) was determined. Biased and unbiased platelet phospho-proteomic profiling examined the OR2L13 signaling pathway.

Results:
169 molecular hits were identified exceeding the 25% threshold, of which 6 ligands (CCF0054500, CCF0054432, CCF0053070, CCF0052249, CCF0051970 and CCF0058399) were persistently specific for OR2L13. Only CCF0054500 suppressed platelet aggregation and α-granule exocytosis through P2Y
12,
PAR1, TP and GPVI receptors suggesting a downstream common mediator. In a murine cremaster arterial injury model, platelet accumulation at the injury site was reduced by 88.9% by CCF0054500 than vehicle (P<0.0003) without altering fibrin generation. CCF0054500 had no impact on hemostasis in mice (tail bleeding assay). CCF0054500 inhibited HRPR through P2Y
12,
PAR1, TP and GPVI in patients with CAD and PAD, even when taking other anti-platelet agents. Phospho-proteomics revealed CCF0054500 phosphorylates heat shock protein 27 (HSP27) which depolymerizes platelet actin cytoskeleton that we further validated by clot retraction assay (CCF0054500 70.6 area vs. 5.2 area vehicle. P<0.0001), and this protective effect is reversed by an HSP27 inhibitor, area 3.56, P<0.0001)

Conclusion:
We identified the first non-olfactory ligand therapeutic that is bioavailable to engage a platelet OR and inhibit platelet activation and thrombosis via HSP27-mediated cytoskeleton rearrangement. Furthermore, CCF0054500 suppresses platelet reactivity irrespective of the receptor-stimulated and circumvents the issue of HRPR in patients with established vascular disease.
Abstract 4146606: Complication Rate of Fractional Flow Reserve-guided Angiography in Comparison to Standard Angiography: A Systematic Review and Meta-Analysis
Authors: Abdulelah Ahmed , Abu Orabi Zeina , Toubasi Ahmad , Hasuneh Manar , Abdulelah Zaid , Nadir M. Adnan
Published: November 2024

Background:
Intracoronary measurement of fractional flow reserve (FFR) has demonstrated higher sensitivity and better negative predicative value in evaluation of coronary artery disease than visual/angiographic only evaluation. Nonetheless, there is profound lack of evidence in the available literature that discusses the rate of complications when utilizing FFR versus standard angiography.

Research Question:
Does FFR carry higher or lower risk of procedural complications when compared with standard angiography?

Aim:
Compare the risk of complications encountered in FFR guidance in comparison to angiography only.

Methods:
The following databases were searched; PubMed, SCOPUS, CENTRAL, Web of Science. The following keywords were used; ((Fractional flow reserve OR FFR) AND (Adverse effect OR Complication)). The studies were included if they compared Angiography-guided Percutaneous Coronary Intervention (PCI) and Fractional Flow Reserve (FFR)-guided PCI in terms of mortality or Major Adverse Cardiac Events (MACE). Case reports and series, animal studies, reviews and non-English articles were excluded from this study. The exposure of interest was FFR-guided PCI whereas the outcomes of interest were MACE and mortality.

Results:
A total of 1,822 articles were identified. After removing duplicates, initial screening, and secondary screening, 15 articles were included and the total number of included patients was 421,291. The percentage of patients who underwent FFR guidance was 3.5% whereas the rest underwent angiography only. Male predominance was noted in both, FFR and angiography. The mean age of the patients who underwent FFR and angiography was 64.9 ± 9.1 and 65.2 ± 9.3 years, respectively. The model that compared between angiography only and FFR in MACE (14 studies) showed that FFR was significantly associated with lower risk of MACE compared to angiography (RR=0.62, 95%CI:0.48-0.81); this model also showed significant heterogeneity (P-value<0.001, I2=80%). 14 studies were included in the model comparing between angiography and FFR in terms of death which showed that FFR was significantly associated with a lower risk of death in comparison with angiography only (RR=0.60, 95%CI:0.41-0.89); this model also showed significant heterogeneity (P-value<0.001, I2=72%).

Conclusion:
The currently available literature demonstrates that, despite the significant heterogenicity, MACE and mortality are substantially lower in FFR in comparison to angiography only guidance.
Abstract 4146625: Automated Detection and Measurement of Aortic Aneurysms in a Clinical Population
Authors: Dinsmore Ian , Luo Jonathan , Triffo William , Ryer Evan , Elmore James , Carey David , Mirshahi Tooraj
Published: November 2024

Introduction:
Aortic aneurysms (AA*) are enlargements of the aorta that can be life-threatening if left untreated. Early detection is essential and typically relies on imaging. However, routine screening is only performed for at-risk groups, such as older male smokers. Computed tomography (CT) scans performed for other reasons could be used to enhance early AA* detection. This could lead to significantly increased screening rates and reduce AA* related deaths.

Hypothesis:
A subgroup of the clinical population who would not undergo routine screening for AA* will have a CT showing aortic ectasia or an aortic aneurysm.

Goals:
To automatically measure aortic diameters from routine CT imaging on a large scale and provide early AA* detection.

Methods:
We trained a deep-learning model on a public dataset of 982 CT scans split into 933 training/validation samples and 49 independent testing samples. We segmented the aorta in both non-contrast and contrast CT images and applied real-time image augmentation during training to enhance the data. The aorta segmentation model achieved a Dice Similarity Coefficient of 0.96 during training, and 0.95 during testing. Using an automated centerline analysis, we measured the maximum cross-sectional diameter of the thoracic (ascending and descending), and abdominal aorta.

Results:
We extracted 34,805 unique abdominal and 26,629 unique chest CTs and measured aortic diameter in each scan. Men had significantly larger abdominal and thoracic aortic diameters than women (p-value < 1e-26, unpaired t-test): ascending: 37.9±4.3 vs 34.2±4.0mm; descending: 31.5±4.2 vs 27.8±3.7mm; abdominal: 24.4±7.0 vs 20.0±4.1mm (men vs women, mean±SD). We manually reviewed 51 ascending, 51 descending, and 91 abdominal aorta diameters. We compared the diameters to the automatic measurements, finding mean absolute errors of 1.6mm, 1.0mm, and 2.8mm, respectively. Evaluating this cohort against ICD10 codes showed that out of 1,362 patients with an abdominal diameter > 3cm, 277 (20%) did not have a AAA diagnosis. Out of 1,126 patients with a descending diameter > 4cm or an ascending diameter > 4.5cm, 386 (34%) did not have a TAA diagnosis. Using existing CT images, we identified a large number of subjects who may be at risk for AA* but have not received routine screening for the disease.

Conclusions:
By using a deep-learning segmentation model on CT imaging, we can automatically and accurately measure aortic diameter and detect AA*.
Abstract 4146626: CYP2C19 Genotyping Decreases 5 and 10-year Mortality in Patients With History of In-Stent Restenosis Undergoing Percutaneous Coronary Intervention
Authors: Patel Dev , Ali Bilal , Sattouf Zafer , Datla Sanjana , Patel Roshan , Adams Julie , Arora Shilpkumar
Published: November 2024

Introduction:
CYP2C19 genotyping is a genetic test that checks for variations in the gene that codes for an enzyme that metabolizes clopidogrel. Testing has been shown to accurately predict response to clopidogrel; however, the impact of testing on mortality is not currently known.

Hypothesis:
Our objective was to compare the mortality among patients with a history of in-stent restenosis after percutaneous coronary intervention and initiation of dual antiplatelet therapy who have undergone CYP2C19 genotyping to those who have not undergone CYP2C19 genotyping. We hypothesize that patients who underwent CYP2C19 genotyping will have decreased 5 and 10-year mortality.

Methods:
A large retrospective database, Trinetix, was used to identify patients aged greater than 18 years old with a history of in-stent restenosis after percutaneous coronary intervention and initiation on dual antiplatelet therapy with either CYP2C19 genotyping or without CYP2C19 genotyping. Two cohorts were subsequently followed depending on if genotyping was performed. Student’s t-test was performed to compare baseline characteristics between cohorts. Demographics and comorbidities were used for 1:1 propensity matching. Kaplan-Myer curves and hazard-ratios were calculated to compare 5 and 10-year mortality.

Results:
Patients that underwent CYP2C19 genotyping (n=144) and did not undergo CYP2C19 genotyping (n=35,039) were propensity matched yielding 142 patients per cohort. In patients with a history of in-stent restenosis, CYP2C19 genotyping was associated with a decreased 5-year mortality (18.98% vs 29.93%; HR=0.542; 95% CI [0.331, 0.887], log-rank p= 0.0134) and 10-year mortality (23.36% vs. 34.31%; HR=0.542; 95% CI [0.345, 0.852], log-rank p=0.0071) compared to no CYP2C19 genotyping.

Conclusion:
In patients with a history of in-stent restenosis, undergoing CYP2C19 genotyping was associated with a decreased risk for mortality when compared to not undergoing CYP2C19 genotyping. Prospective randomized trials are needed to further guide patient selection for CYP2C19 genotyping.
Abstract 4146633: Catheter-Directed Intervention for High-Risk Acute Pulmonary Embolism in Patients with Cancer: Findings from the U.S. Nationwide Readmissions Database
Authors: Kumar Manoj , Ali Shafaqat , Nso Nso , Jamshed Aneeza , Murthi Mukunthan , Kumar Nomesh , Ricciardi Mark , Arman Qamar , Gomez Valencia Javier
Published: November 2024

Background:
Catheter-Directed Interventions (CDIs) for Acute Pulmonary Embolism (PE) have been present for years but their use is limited due to paucity of data especially in patients with cancer. We examine the safety and efficacy of CDIs in patients with high-risk PE and cancer.

Methods:
Nationwide Readmissions Database (2016-2021) was used to analyze cancer patients presenting with high-risk PE (HR-PE) (shock, pressor or mechanical circulatory support requirement). Patients who received systematic thrombolysis were excluded. Mahalanobis Distance Matching within the Propensity Score Caliper was used to match patient who received CDIs vs those who were treated with anticoagulation alone. Inverse Probability weighting (IPW) was utilized, and Pearson’s chi-squared test was applied to the PSM-2 matched cohorts to compare outcomes.

Results:
Among 265,196 hospitalization of cancer patients with HR-PE, X were treated with systemic thrombolysis and 795 (0.3%) of the patients underwent CDI.

After propensity matching (N: 421 in each group), patients receiving CDI had a significantly lower mortality (33% vs. 41.8%, aOR:0.76 (95% CI, p: 0.008); However, bleeding complications including major bleeding (10.7% vs 6.2%, aOR:1.97 (95% CI, p: 0.018) was higher in patients receiving CDIs. No difference was observed in the risk of intracerebral hemorrhage (p>0.05). Readmission rates were similar at 30-day and 90-day intervals (p>0.05). From 2016-2021, mortality associated with HR-PE in cancer has not changed significantly (p>0.05); however, mortality in patients undergoing CDIs has decreased from (43.8% to 22.6%, p-trend: 0.0004). There has been increasing use of mechanical thrombectomy (MT) over thrombolysis in recent years.

Conclusion:
CDIs for HR-PE in cancer patients are associated with significant reduction in mortality and associated with higher bleeding. Mortality has decreased across the years for patients undergoing CDIs with higher utilization of MT.
Abstract 4146638: Comparative Assessment of hsCRP and Apolipoprotein B as ASCVD Risk Biomarkers
Authors: Amusat Saheed Oladele
Published: November 2024

Introduction/Background:
According to the American Heart Association, the accumulation of plaque in the walls of arteries is identified as the primary cause of atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein B (apo B) has been identified as a more precise cardiovascular risk marker than LDL-C, while high-sensitivity C-reactive protein (hsCRP) has shown potential as a cardiovascular disease indicator.

Research Questions/Hypothesis:

Goals/Aims:
To investigate the diagnostic performance and routine screening cut-off of hsCRP for early ASCVD risk in adult patients, comparing it with Apo B.

Methods/Approach:
A sample of 494 individuals from the NHANES 2015-2016 laboratory dataset, with a mean age greater than 17 years, was used for this study. ASCVD risk was measured by non-HDL-C, categorized into low and high risk based on the Mayo Clinic reference range. Predictors included apo B, and hs-CRP. Binomial logistic regression and ROC curve analyses were conducted using the generalised linear models and pROC packages in RStudio IDE. Hypotheses were validated at p≤0.05, and diagnostic performance metrics such as ROC AUC, sensitivity, and specificity were measured on a scale of 0-1.

Results:
The findings revealed that for every 1g/L increase in apo B concentration, the odds of high ASCVD risk were approximately 3.8 ×1011 times higher. Additionally, the model indicated that the odds of high ASCVD risk were 1.03 times higher for every 1mg/L increase in hsCRP concentration. However, this indicates that hsCRP level was not associated with odds of ASCVD risk. The ROC AUC for apo B and hsCRP were approximately 0.9739 and 0.6165, respectively, with cut-off values (sensitivity, specificity) of approximately 0.9g/L (0.927, 0.897) and 2.4 mg/L (0.596, 0.601), respectively. Thus, levels above these thresholds for both apo B and hsCRP are associated with high ASCVD risk.

Conclusion(s):
The study demonstrates that apo B exhibits high discriminatory and diagnostic accuracy, making it a suitable ASCVD risk biomarker compared to hsCRP. While hsCRP shows moderate diagnostic accuracy, it is not sufficient as a standalone ASCVD risk diagnostic marker. Therefore, apo B could serve as a replacement for LDL-C, while hsCRP could possibly serve as an add-on test in ASCVD risk assessment.
Abstract 4146645: Evaluating Patterns of Impedance Drop for Optimal Lesion Formation in Pulmonary Vein Isolation for Atrial Fibrillation
Authors: Okuyama Yusuke , Ueda Kouhei , Kazuma Toshiki , Mimura Naomitsu , Hattori Daisuke , Sugimoto Miyu , Takahara Chisaki , Kashou Keikoku , Tamura Atsushi , Jikan Masahiko , Nakajima Kanta , Masuda Kazunori , Matsuoka Shunzo , Nakagawa Yoshihisa
Published: November 2024

Introduction:
Ablation index (AI) has been used as a predictor of forming durable lesions in pulmonary vein isolation (PVI) for atrial fibrillation (AF). Impedance drop (ID) had also been thought to be important for adequate lesion formation with radio frequency application (RF). However, relationship of ID and AI is unclear because AI does not take into account ID. In addition, there are some modes of ID, but it is unclear that what modes of dropping impedance is effective. Here, we investigated which modes of dropping impedance was effective for acute successful lesion formation. Association of ID and parameters of ablation lesion with RF including AI was also evaluated.

Methods:
Ablation lesions made by RF using 35W power during PVI were studied. Only lesions created for the initial PVI line were analyzed. These points were classified into 5 groups according to the ways of ID. Points with gradual ID, 2-phased ID, and steep ID were respectively classified as group 1, 2, and 3, and these three groups were investigated. Points without dropping impedance, increase in impedance, or RF duration of less than 5 seconds were excluded. Acute success rate, decrease in impedance, duration of RF, average contact force (CF) and value of AI were investigated for each group.

Results:
From 40 consecutive cases, 1921 lesions were obtained, of which 1843 were investigated. Group 1, 2, and 3 consisted of 511, 1184, and 148 points, respectively. Acute success rate for each group were 93.0, 98.6, and 93.2%, and was the highest in groups 2 (p<0.05). AI in group 2 was the highest among three groups (464±47 vs. 476±51 vs. 467±66 for each group, p<0.05). ID and CF were the largest in group 3 among three groups (7.6±3.5 vs 12.2±5.2 vs 14.6±5.9 ohm, p<0.05, for each group. 12.8±5.2 vs 15.0±6.0 vs 17.6±8.3 g, p<0.05, for each group). The duration of RF was longest in group 1 among three groups (24.5±4.7 vs 23.6±4.6 vs 21.0±6.2, p<0.05, for each group).

Conclusion:
For optimal lesion formation, to obtain 2-phased ID in combination with moderate CF, ID, and the duration of RF was important. Evaluating modes of ID may make AI more reliable to create optimal lesions with RF at 35W of power.
Abstract 4146655: Transcatheter device closure of Ventricular Septal Defect in children weighing less than 30 lbs. is a safe and effective procedure based on 10-year experience from a single tertiary center in southern India
Authors: Saha Shubhashis , Mandal Amit , George Oommen K
Published: November 2024

Introduction:
Ventricular septal defect (VSD) is the most common pediatric defect which benefits from closure at an early age. This study describes the procedural and follow-up data from a 10-year experience of VSD device closure at a tertiary referral center in southern India.

Methods:
We conducted a retrospective clinical data review of all pediatric patients who underwent transcatheter device closure for isolated VSD in the past ten years, from May 2014 to May 2024. We included patients with body weights less than 30 lbs. and excluded patients with VSD diameter >10mm and those with other congenital cardiac anomalies.

Results:
We included 40 patients with a mean age of 18.95 ± 13.02 months, mean weight of 17.87 ± 6.64 lbs. and male:female ratio of 23:17 (Table 1). The most common symptom at presentation was failure to thrive (22, 55.0%), and five patients (12.5%) had VSD associated with Downs syndrome. 34 (85%) children had perimembranous VSD, and the rest had muscular VSD (6, 15.0%). The mean VSD size was 6.01 ± 2.29 mm, with a mean peak gradient of 49.55 ± 23.57 mm Hg. Either Amplatzer ADO II (14, 35.0%) or Lifetech Konar MF (26, 65.0%) devices were used, mainly via the retrograde approach (37, 92.5%) with a mean total fluoroscopy time of 21.82 ± 10.01 mins. Complications associated with the procedure were minimal (as in Table 2), with 77.5% (31 of 40) patients having no residual shunts at their follow-up ECHO after 6 months.

Conclusions:
Transcatheter VSD device closure is a safe and effective procedure in young children weighing less than 30 lbs., with minimal complications and good outcomes at follow-up.
Abstract 4146682: Rarer Than Rare: AL Amyloidosis Presenting as Abdominal Amyloidomas
Authors: Wahaj Ahmed , Maqsood Naima , Ehya Hormoz , Varshavsky Yanovsky Asya , Fabrizio Carly
Published: November 2024

Case:
A 52-yr-old man with weight loss and urinary hesitancy for 4 months underwent a CT urogram. No urologic abnormalities were noted but there was an incidental finding of intraperitoneal nodules and a perigastric mass. Biopsy of the perigastric lymph nodes showed abundant amyloid deposits, consistent with amyloidoma. Systemic amyloidosis workup was started. Serum immunofixation showed an IgG lambda M spike of 0.1 g/dL, and serum free light chain ratio was 0.17 (k/l = 10/60, mg/L). The tumor board recommended biopsy of other abdominal sites to distinguish plasmacytoma from amyloidoma. Biopsy showed amyloidosis with benign reactive lymph nodes and small clusters of lambda restricted plasma cells suggesting amyloidoma/plasmacytoma. Bone marrow biopsy showed 15% plasma cells, confirming multiple myeloma/amyloidosis overlap. Daratumumab-cyclophosphamide-bortezomib-dexamethasone (DARA-CyBorD) induction therapy was initiated. Transthoracic echocardiogram (TTE) showed normal biventricular function and moderate concentric hypertrophy. A cardiac MRI (CMR) then confirmed features of early amyloidosis. Light chains normalized with therapy but repeat bone marrow biopsy showed 5% lambda restricted plasma cells. Given the biopsy results and cardiac amyloid, consolidative autologous stem cell transplant was pursued to achieve a deep hematological response.

Discussion:
AL amyloidosis is a rare but fatal disease. Cardiac involvement is seen in > 75% patients and degree of cardiac infiltration determines median survival. The initial presentation of intra-abdominal amyloidomas is highly unusual and only reported in case series in literature. A finding of amyloidoma should prompt workup for systemic amyloidosis. Cardiac workup should be undertaken even in the absence of overt symptoms. TTE findings in early cardiac amyloid are highly non-specific and can, therefore, be easily missed. A high index of suspicion is needed in this cohort with advanced imaging being pursued for any abnormality such as moderate concentric hypertrophy. Recognition of early cardiac involvement was key in deciding the chemotherapy regimen and in the decision to pursue autologous stem cell transplant for long term remission.
Abstract 4146689: Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program
Authors: Desai Milind , Seto Dewey , Cheung Michael , Coiro Michele , Patel Niki , Bastien Arnaud , Lockman Jeffrey , Afsari Sonia , Martinez Matthew
Published: November 2024

Introduction:
Mavacamten is a cardiac myosin inhibitor approved by the US FDA for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms. Under the risk evaluation and mitigation strategy (REMS) program, patients taking mavacamten are required to be monitored for development of systolic heart failure (HF), with interruption if left ventricular ejection fraction (LVEF) decreases to <50%.

Aims:
We report updated results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024), including safety data for patients treated for ≥1 year.

Methods:
Data on health care providers and pharmacy certification, patient monitoring (including health status forms and echocardiograms), and screening for drug interactions prior to each dispense were collected.

Results:
Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; ages were <18 (0.1%), 18-40 (6.3%), 41-60 (29.0%), and ≥61 years (64.6%). Of 5,573 patients with submitted health status forms as of 27-Feb-2024, 256 (4.6%; Figure A) experienced a decrease in LVEF to <50% and 71 (1.3%) experienced HF requiring hospitalization (HFH). On the 29,111 status forms, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment (Figure B), 78 (4.04%) had an LVEF reduction to <50% and 4 (0.21%) experienced LVEF <50% + HFH (with potential confounders like atrial fibrillation) but later resumed treatment. A planned dosing analysis will provide further insights. Of 52,432 drug interaction checklists completed, 130 (0.25%) resulted in mavacamten dose reduction and 167 (0.32%) resulted in discontinuation of a concurrent medication.

Conclusions:
In >6,000 patients during the first 22 months of the REMS Program for mavacamten, the need for temporary interruption for LVEF <50% was very low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH. Additionally, a low proportion of patients had potential drug-drug interactions, with a low number requiring a mavacamten dose reduction. The data suggest favorable real-world experience with mavacamten, confirmed by REMS oversight.
Abstract 4146703: Conservative versus invasive management of spontaneous coronary artery dissection: A meta-analysis of 7197 patients
Authors: Abdelaziz Ahmed , Gadelmawla Ahmed Farid , Helmi Ahmed , Diaa Ahmed , Ibrahim Rahma AbdElfattah , Mohamed Ahmed , Afify Raneem , Desouki Mariam , Nasr Ahmed , Banour Sandi , Abdelazeem Basel
Published: November 2024

Background:
Spontaneous coronary artery dissection (SCAD) is defined as a separation of the coronary arterial wall caused by intramural bleeding that is neither traumatic, iatrogenic, nor atherosclerotic. It is now recognized as a significant cause of acute coronary syndrome (ACS), particularly in young women. There is conflicting information regarding the acute therapy of SCAD. We aimed to summarize the available evidence and provide a comprehensive analysis of the management of SCAD.

Methods:
We systemically examined the clinical outcomes of conservative and invasive management of patients with SCAD using medical records from Web of Science, PUBMED, Scopus, and Cochrane. Our outcomes of interest were all-cause mortality, non-fetal myocardial infarction (MI), and target vessel revascularization (TLR). Risk ratios (RR) and 95% CI were used in a random-effects model to analyze the data.

Results:
A total of 27 studies were included in this meta-analysis, with a total sample size of 7,197. The conservative approach was associated with a reduction in all-cause mortality compared to the invasive method (RR = 0.29, 95% CI [0.20, 0.42], P < 0.001), and non-fetal MI (RR = 0.74, 95% CI [0.55, 0.99], P = 0.04). Moreover, the conservative approach was associated with a reduced incidence of TLR over the invasive approach (RR = 0.53, 95% CI [0.37, 0.77], P = 0.009).

Conclusion:
Conservative management of patients with SCAD showed better clinical outcomes than invasive management. We detected lower rates of death, myocardial infarction, and target vessel revascularization among the conservatively managed group, which suggests that conservative therapy should be the first-line approach for patients with SCAD.
Abstract 4146709: TMEM65 regulates NCLX-dependent mitochondrial calcium efflux to limit pathogenic mitochondrial calcium overload
Authors: Garbincius Joanne , Salik Oniel , Cohen Henry , Choya-Foces Carmen , Mangold Adam , Makhoul Angelina , Schmidt Anna , Khalil Dima , Doolittle Joshua , Wilkinson Anya , Murray Emma , Lazaropoulos Michael , Hildebrand Alycia , Tomar Dhanendra , Elrod John
Published: November 2024

Introduction:
Mitochondrial calcium (
m
Ca
2+
) exchange regulates energy metabolism, but if perturbed causes
m
Ca
2+
depletion and energy starvation or
m
Ca
2+
overload and cell death. The mitochondrial sodium (Na
+
)-calcium exchanger, NCLX, is critical for
m
Ca
2+
efflux in the heart, and animal models support NCLX as a therapeutic target to limit pathogenic
m
Ca
2+
overload. However, the mechanisms that regulate NCLX activity are largely unknown, representing a key barrier to translation.

Goal:
We used proximity biotinylation screening to identify the NCLX interactome and define novel regulators of NCLX function.

Hypothesis:
Our screen identified the mitochondrial inner membrane protein, TMEM65, as an NCLX-proximal protein that potently enhances Na
+
-dependent
m
Ca
2+
efflux. Therefore, we hypothesized that TMEM65 promotes
m
Ca
2+
efflux through NCLX.

Approach:
We measured
m
Ca
2+
exchange in AC16 cardiomyocytes with TMEM65 overexpression (OE) or CRISPR/Cas9 genetic disruption of
TMEM65
to test its effect on
m
Ca
2+
efflux, and used pharmacologic inhibition and genetic knockout to determine TMEM65’s functional dependence on NCLX. We evaluated TMEM65’s impact on murine cardiac function
in vivo
using an AAV9-shRNA knockdown strategy.

Results:
Deletion of
TMEM65
attenuated Na
+
-dependent
m
Ca
2+
efflux, while inhibition or deletion of NCLX ablated the increase in
m
Ca
2+
efflux observed with TMEM65 OE. Proximity ligation assay revealed co-localization of TMEM65 and NCLX in intact cells.
In silico
molecular modeling and co-fractionation of NCLX and TMEM65 via size-exclusion chromatography support their existence in a common macromolecular complex. Mutagenesis studies identified residues N163/D167 as critical to TMEM65 function, suggesting their importance to its cooperation with NCLX.
TMEM65
expression decreased in human and murine heart failure, and
Tmem65
KD in mice promoted myocardial
m
Ca
2+
overload and impaired cardiac function. Notably, TMEM65 OE mitigated necrotic cell death during cellular Ca
2+
-overload
in vitro
.

Conclusions:
Loss of TMEM65 function disrupts NCLX-dependent
m
Ca
2+
efflux, causing pathogenic
m
Ca
2+
overload, cell death and organ-level dysfunction, whereas gain of TMEM65 function can attenuate these effects. Our findings demonstrate the essential role of TMEM65 in maintaining
m
Ca
2+
efflux and suggest modulation of TMEM65 as a novel therapeutic strategy to control
m
Ca
2+
homeostasis in heart failure and other pathologies featuring dysregulated
m
Ca
2+
exchange.
Abstract 4146711: A meta-analysis of myocardial recovery and its associated factors in advanced heart failure with left ventricular assist device
Authors: Hasabo Elfatih , Isik Burce , Bakr Mohamed , Mahmmoud Fadel Allah Mohammed , Neiroukh Dina , Nosir Mahmoud , Ayhan Cagri , Sultan Sherif , Caliskan Kadir , SOLIMAN OSAMA
Published: November 2024

Introduction:
Patients with advanced heart failure use left ventricular assist devices (LVAD) to improve their outcomes and enhance the reverse remodeling of the heart. There has been no previous meta-analysis on the percentage or predictors of myocardial recovery after LVAD according to the device strategy. This study aims to find the pooled percentage and determinants of myocardial recovery after LVAD.

Methods:
A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to April 2024. We used relevant keywords to include the studies that reported the percentage of people who have achieved myocardial recovery after LVAD. The percentage of participants using LVAD and achieved myocardial recovery was extracted and pooled results were stratified according to the device strategy. RevMan 5.4 was used for the meta-analysis.

Results:
We included 30 studies comprising 38708 patients with various LVADs used among the participants. Across the studies, multiple terms for myocardial recovery were used, most commonly being device explant following myocardial recovery and achieving left ventricular ejection fraction (LVEF) ≥40% after using LVAD. The overall pooled percentage of people who achieved myocardial recovery was 4.61% (95% CI [3.77, 5.45]), and the result was heterogeneous (I2 = 93%, p <0.00001). The percentage of myocardial recovery in patients implanted as a bridge to recovery (BTR) was 24.8%, 11.1% for a bridge to transplant (BTT) and 2.9% for mixed device strategy (Figure 1). Shorter duration of heart failure, female gender, younger age, absence of implantable cardioverter-defibrillator (ICD), and low left ventricular end-diastolic diameter (LVEDD) were the most cited factors associated with myocardial recovery.

Conclusion:
Myocardial recovery following LVAD is low and was found to be high in patients implanted for BTR. Several factors have been identified as potential predictors of myocardial recovery in patients on LVAD therapy. Further action should be taken to improve the recovery among this population.
Abstract 4146716: Radial Versus Femoral Access for Mechanical Thrombectomy in Patients with Stroke: A Systematic Review, Meta-Analysis and Meta-Regression
Authors: Odat Ramez , Hussein Ayham , Idrees Muhammad , Aldalati Abdullah , Al Zoubi Bashar M. , Haneyah Dania , Zahra Rubab , Alshwayyat Sakhr , Yasin Jehad , Sabet Cameron , Nguyen Dang
Published: November 2024

Background:
Femoral access is predominantly used for mechanical thrombectomy in stroke patients with large vessel occlusions. Following interventional cardiology guidelines, routine radial access has been proposed as an alternative, though its safety and efficacy remain controversial. We aimed to evaluate the efficacy and safety of radial versus femoral access for mechanical thrombectomy in patients with stroke.

Hypothesis:
In mechanical thrombectomy for stroke patients with large vessel occlusions, could the transradial access (TRA) result in comparable efficacy but fewer access site complications compared to transfemoral access (TFA)?

Methods:
A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to May 2024, to identify studies measuring the efficacy and safety of radial versus femoral access for mechanical thrombectomy in patients with stroke. The meta-analysis was performed using the Review Manager and Open Meta Analyst.

Results:
Ten studies (2,277 participants) were included in the review. There were no significant differences between radial and femoral access in terms of successful recanalization (0R: 1.01; 95% CI, 0.59,1.73; p=0.98), complete recanalization (OR: 1.08; 95% CI, 0.60,1.94; p=0.81), favorable functional outcomes (0R: 0.86; 95% CI, 0.53,1.41; p=0.56), first-pass reperfusion (OR: 0.89; 95% CI, 0.67,1.19; p=0.44), number of passes (MD: 0.10; 95% CI, -0.13,0.33; p=0.4), access-to-reperfusion time (MD: -3.92; 95% CI, -9.49,1.65; p=0.17), or symptomatic intracranial hemorrhage (OR: 0.95; 95% CI, 0.55,1.65; p=0.86). However, access site complications were significantly less frequent in the TRA group as compared with the TFA group (OR: 0.21; 95% CI, 0.08,0.60; p=0.004). Meta-regression showed no significant associations for publication year, mean age, gender, or baseline NIHSS scores with clinical outcomes.

Conclusion:
This meta-analysis indicates that TRA and TFA provide comparable outcomes in mechanical thrombectomy for acute ischemic stroke, with TRA resulting in fewer access site complications. Further large-scale randomized trials are recommended to confirm these findings and potentially support a shift towards TRA in neurovascular procedures.