bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4144702: Gender Disparities in Outcomes of Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI) who have also received Chemotherapy: An Analysis of National Inpatient Sample (NIS) Data from 2016-2021
Authors: Uttam Chandani Kanishka , Agrawal Siddharth , Raval Maharshi , Bhargava Sahil , Patel Yug , Siddiq Sajid
Published: November 2024

Background:
Gender disparities in outcomes for patients undergoing Transcatheter Aortic Valve Implantation (TAVI) with concomitant chemotherapy remain under-explored. This study investigates these disparities, focusing on mortality, procedural complications, and baseline characteristics.

Methods:
We conducted a retrospective analysis using data from the National Inpatient Sample (NIS) from 2016 to 2021. Gender differences in outcomes were examined in patients undergoing TAVI who have also received chemotherapy. Multivariate logistic regression was utilized for outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with statistical significance determined by P-values.

Results:
The study included 7,275 patients, comprising 3,375 males and 3,900 females. The mean age was similar between males (76.19 years) and females (75.81 years). Outcome analysis revealed no significant gender difference in in-hospital mortality (OR: 1.63, 95% CI: 0.464-5.725, P = 0.445), heart block (OR: 1.061, 95% CI: 0.849-1.326, P = 0.6) or vascular injury (OR: 1.065, 95% CI: 0.572-1.981, P = 0.841). However, females had significantly higher odds of bleeding (OR: 1.601, 95% CI: 1.161-2.207, P = 0.004) and respiratory failure (OR: 1.792, 95% CI: 1.028-3.126, P = 0.04). Additionally, females had higher odds of sudden cardiac arrest (OR: 8.181, 95% CI: 1.092-61.26, P = 0.041) but lower odds of atrial fibrillation (OR: 0.689, 95% CI: 0.543-0.875, P = 0.002) and arrhythmia (OR: 0.537, 95% CI: 0.344-0.837, P = 0.006). Length of stay was longer for females (Coefficient: 0.515, 95% CI: 0.137-0.893, P = 0.008), but total charges did not differ significantly between genders (Coefficient: 2321, 95% CI: -10371.11-15013.54, P = 0.72).

Conclusions:
Significant gender disparities exist in specific procedural outcomes for patients undergoing TAVI who have also received chemotherapy. Females were at higher risk for bleeding, respiratory failure, and sudden cardiac arrest, while having lower rates of atrial fibrillation and arrhythmia compared to males. These findings highlight the necessity for gender-specific risk assessment and management strategies to improve outcomes for patients undergoing TAVI with chemotherapy.
Abstract 4144743: From Tummy Trouble to Heart Hassle: A Case of Traveler's Diarrhea Triggering Myopericarditis
Authors: Guynn Nicole , Dietzen Alarica , Chuckaree IshwaR , Loyd Quentin , Garcia Mariana , Ogunniyi Modele
Published: November 2024

Case description:
>A 38-year-old male with a history of paroxysmal atrial fibrillation status post-RFA ablation, presented to the emergency department (ED) with a 3-week history of non-bloody diarrhea, abdominal cramping, nausea, fever, and headache after a trip to Guatemala. In the ED, his vital signs were temperature (99.3 °F), and heart rate (116 bpm). Notable physical exam findings were diffuse erythematous macular rash and conjunctival injection. Initial labs demonstrated elevated white count (15,100 K/mcL) and lactate (3.2 mmol/L). He was treated with ceftriaxone and metronidazole, with clinical improvement. Stool cultures were positive for salmonella and cyclospora cayetanensis. On hospital day 3, he developed severe substernal chest pain, minimal ST elevation in the anterolateral leads on ECG and elevated HS- troponin levels of 7000 ng/ml, peak of 12000 ng/ml. Transthoracic echocardiogram showed normal LV systolic function, with no evidence of pericardial effusion and regional wall motion abnormalities. Subsequent cardiac MRI demonstrated evidence of myopericarditis(anterior and lateral pericardial enhancement, along with focal epicardial late gadolinium enhancement in the mid inferolateral wall of the left ventricle with associated myocardial edema, and a small pericardial effusion). He was discharged home on Trimethoprim-Sulfamethoxazole and started on colchicine, with no recurrent chest pain.

Discussion:
Myopericarditis is a complication of acute pericarditis due to pericardial inflammation extension to the myocardium. It is usually caused by a virus and rarely due to bacteria as demonstrated by this case, presenting as elevated troponin levels and ST-segment elevation on ECG. To our knowledge, there are no known reports of cyclospora cayetanensis causing myopericarditis. The adherence of the salmonella bacteria to the cardiac endothelium can result in myocyte necrosis and release of self-antigens leading to the development of antibodies and autoimmune myocarditis. Long-term management of bacterial myopericarditis is dependent on the severity of the clinical presentation and includes antibiotics, anti-inflammatory medications, and colchicine. Most patients recover within one month, but persistent cardiac dysfunction and progression to end-stage dilated cardiomyopathy can occur, thus follow-up echocardiography is recommended.
Abstract 4144825: 4-Hydroxy-2-Nonenal Alters Alternative Polyadenylation to Regulate mRNA Isoform Diversity in the Transition from Human Cardiac Fibroblasts to Myofibroblasts
Authors: Natarajan Kartiga , Neupane Rahul , Yalamanchili Hari Krishna , Palaniyandi Suresh , Wagner Eric , Guha Ashrith , Amirthalingam Thandavarayan Rajarajan
Published: November 2024

Background:
Cardiac fibrosis involves excessive deposition of extracellular matrix (ECM) proteins, leading to myocardial stiffness and remodeling, exacerbating diastolic and systolic dysfunction. Notably, cardiac fibroblast (CF) differentiation into myofibroblasts drives ECM deposition, contributing to adverse remodeling. Lipid peroxidation by 4-hydroxynonenal (4HNE) is crucial in fibrosis initiation. Our research explores the role of alternative polyadenylation (APA) in ECM production specifically the impact of 4HNE on APA-mediated modifications in CF activation.

Objective:
To investigate global APA events during the transition of human CFs to myofibroblasts induced by 4HNE, using the PolyA miner algorithm.
Methods:
Human CFs were treated with 1 or 2 µM 4HNE or vehicle control to investigate 4HNE induced heterogeneity in 3’UTR lengths. Poly(A)-click RNA sequencing and PolyA-miner analysis were used to examine 3’UTR length changes in genes related to myofibroblast activation.

Results:
Our analysis revealed cells treated with 1 µM 4HNE altered 236 differential APA genes (DAGs), of which 169 genes exhibited PolyAIndex and among them, 77 underwent 3’ UTR lengthening, and 92 genes underwent 3’UTR shortening. Whereas cells treated with 2µM 4HNE altered 461 DAGs of which 345 genes exhibited PolyAIndex, with 127 genes exhibiting elongation and 218 genes showing shortening. This shows, 4HNE altered 3’UTR lengths in dose dependent manner. Importantly, pathway analysis unveiled that the shortened 3’UTR lengths of genes in 4HNE treated fibroblasts were associated with TGF-β, hippo, and focal adhesion signaling pathways implicated in myofibroblast activation, whereas genes with altered elongated 3’UTR lengths were mostly linked to hedgehog signaling. Furthermore, 4HNE promoted differential APA of fibrotic genes, including fibronectin, collagen 1 α, and α-smooth muscle actin, correlating with increased protein expression. Altogether, our results identify 4HNE as an APA regulator during cardiac myofibroblast activation, though the exact mechanism remains unknown.

Conclusion:
This study provides novel insights into the molecular mechanisms by which 4HNE governs the transition of human CF to myofibroblasts through regulation of 3'UTR length of fibrotic genes and subsequent translational control. Understanding 4HNE-mediated APA-mediated changes in CFs may pave the way for the development of targeted therapeutic strategies to mitigate adverse outcomes in cardiac fibrosis.
Abstract 4144868: Optimizing the Care of Patients with Cardiac Amyloidosis in a Safety Net Hospital: A Multidisciplinary Heart Team Approach
Authors: Stephens Joshua , Olakunle Oreoluwa , Crawford Kaylyn , Guynn Nicole , Ford Dimitri , BROWN MATTHEW , WORKS FAITH , Taylor Deborah , Cheeley Mary Katherine , Lopez Carlos , Onuorah ifeoma , Halkar Raghuveer , Amin Sagar , Gibson Briana , Bernal-Mizrachi Leon , Ogunniyi Modele
Published: November 2024

Introduction

Cardiac Amyloidosis is often underdiagnosed due to the heterogeneity of clinical presentation, disease rarity, and clinician unfamiliarity with diagnosis and management. Studies have shown that timely diagnosis and effective treatment can prolong median survival in patients with cardiac amyloidosis. By optimizing cardiovascular care, multidisciplinary heart teams play a significant role in cardiovascular disease management. We describe a multidisciplinary heart team (MDHT) based approach to the diagnosis and management of suspected cases of cardiac amyloidosis in a safety net hospital.

Methods:
A MDHT working group of cardiologists, hematologists/oncologists, nuclear medicine physicians, radiologists, pathologists, nephrologists, advanced practice practitioners, and pharmacists was established to optimize the clinical care of patients with amyloidosis. Virtual monthly interdisciplinary meetings were held from January 2022 to May 2024 to review clinical cases, discuss diagnostic and treatment plans, review cardiac imaging, and implement best clinical practices to improve patient outcomes. Cases were identified based on referrals and consultations.The clinical case presentation was led by cardiology and hematology/oncology fellows. The ACC Cardiac Amyloidosis Expert Consensus Decision Pathway was used to guide management.

Results:
Of the 95 patients who were suspected to have amyloidosis, 44.2% (n=42) were female, and 91.6% self-identified as Black, the median age was 70.5 years. For diagnostic testing, 32.6% (n=31) underwent a PYP scan after light chain AL amyloidosis was rulled out, and 15 patients(15.8%) underwent either cardiac or bone marrow biopsy for concerns of AL amyloidosis. Of the total cohort, 26.32% (n=25) had hereditary transthyretin amyloidosis (hATTR), and 3.16% (n = 3) had AL amyloidosis. Of the patients with confirmed amyloidosis (29.47%, n=28), 67.9% (n=19) received medical therapy [53.57% (n=15) received Tafamidis for hATTR cadiomyopathy and 7.1% (n=2) received chemotherapy for light chain AL amyloidosis.

Conclusion:
A multidisciplinary heart team approach resulted in the diagnosis of cardiac amyloidosis in 26% of our cohort with 68% of the cohort receiving medical treatment. This collaboration has facilitated patient-centered care, comprehensive evaluation and personalized treatment plans for patients with suspected cardiac amyloidosis and also provided educational opportunities for trainees.
Abstract 4144876: Genetic evaluation of metabolic signatures associated with lipid-lowering medications
Authors: Sharma Pranav , Khodursky Samuel , Yuan Shuai , Damrauer Scott , Levin Michael
Published: November 2024

Introduction:
Human genetic studies have identified hundreds of risk loci for circulating lipoproteins, motivating the development of new lipid-lowering medications. Although these targets influence lipids and metabolites through unique mechanisms, the extent to which they exert shared pleiotropic effects on other effectors of atherosclerotic cardiovascular disease remains uncertain. This study explored the lipid subfraction, cytokine, and metabolic signatures associated with lipid-lowering targets using Mendelian Randomization (MR).

Methods:
The study focused on protein targets of novel lipid-lowering medications: PCSK9, APOB, LPA, LPL, and ANGPTL3. Instruments for PCSK9, LPL, and ANGPTL3 were derived from the UK Biobank Pharma Proteomics Project (54,219 participants), and for LPA and APOB from the Pan-UK Biobank (335,796 and 418,505 participants). These exposures were tested against outcomes including 40 cytokines (meta-analysis of 74,783 individuals), 249 lipid-subfraction measures (118,461 UK Biobank participants), and 1,400 metabolite measures (8,299 participants in the Canadian Longitudinal Study on Aging). Univariable MR was performed using the inverse-variance weighted (IVW) method to test associations. The Jaccard index quantified the similarity of effects of each target across these outcomes, focusing on significant results after adjusting for multiple testing (FDR q < 0.05).

Results:
The lipid-lowering targets were each significantly associated with between 1-17 cytokines, 184-220 lipid subfractions, and 307-396 metabolites (FDR q < 0.05). ANGPTL3 and PCSK9 showed the highest similarity of effects on lipid subfractions (Jaccard Index: 0.83, p < 0.001). LPA, APOB, and ANGPTL3 were the only targets with significant cytokine effects, with low similarity scores potentially suggesting their inflammatory signatures are unique. ANGPTL3 and LPA had the highest similarity of effects on metabolites (Jaccard Index: 0.19, p < 0.05).

Conclusion:
Our analyses indicate that lipid-lowering targets influence metabolic signatures through shared and unique mechanisms. Further exploration of how cytokine, lipid, and metabolic profiles are impacted may help in the development of more effective medications.
Abstract 4145379: The Trojan Worm: A Tale of Strongyloides and Eosinophilic Myopericarditis
Authors: Yellapu Vikas , Magid Lindsey , Morgan Michael , Plamenac Jovan
Published: November 2024

We present a perplexing case of a 33-year-old male with no prior cardiac history who presented to the emergency department with a 5-day history of worsening pleuritic chest pain and dyspnea. The patient had recently returned from El Salvador, where he resided near the beach. Notably, his chest pain worsened with inspiration but was not positional. He denied fevers, chills, or family history of cardiac disease, but reported recreational marijuana use.

Initial evaluation revealed normal vital signs and electrocardiogram, but marked eosinophilia (12%) and mildly elevated C-reactive protein. High-sensitivity troponin levels peaked at 8400 ng/L, raising suspicion for myocardial injury. Echocardiography demonstrated preserved left ventricular ejection fraction but revealed a moderate pericardial effusion. Pericardial fluid analysis showed benign reactive mesothelial cells.

Given the patient's travel history and eosinophilia, a broad differential diagnosis was considered, including parasitic etiologies such as Chagas disease. However, serological testing for Chagas was negative. Interestingly, IgG antibodies for Strongyloides stercoralis were positive, implicating strongyloidiasis as the underlying cause of the eosinophilic myopericarditis.

The patient was treated with non-steroidal anti-inflammatory drugs, colchicine, and empiric ivermectin therapy. A cardiac magnetic resonance imaging study was ordered to further characterize the myocardial involvement, but the patient was unfortunately lost to follow-up.

This case highlights the importance of maintaining a broad differential diagnosis and considering travel-related exposures in patients presenting with eosinophilic myopericarditis. Strongyloidiasis, though uncommon, can manifest with cardiac involvement and should be considered in at-risk populations, particularly those with eosinophilia and a compatible travel history.

It is also important to have a high clinical suspcision for stronglodies induced myopericarditis in high risk patinets such as ours as typical treatment with steroids could result in furthur desemination of strongyloidias infection leading to fulminant eosinophillic myocarditis.
Abstract 4145391: Maternal Plasma Proteome: Associations with Blood Pressure during Pregnancy and Postpartum
Authors: Minhas Anum , Bedsaul-Fryer Jacquelyn , Xiong Zhichen , Sincerbeaux Gwen , Schulze Kerry , Kim Hyunju , Ozkan Bige , Ali Hasmot , Shaikh Saijuddin , West Keith
Published: November 2024

INTRODUCTION:
Pregnancy is marked by cardiovascular and hemodynamic changes to enable normal placental-fetal growth but may also predispose women to adverse outcomes including hypertensive disorders. Studies have assessed the plasma proteome of hypertension, but proteomic biomarkers of maternal blood pressure (BP) through pregnancy and postpartum remain unexplored.

OBJECTIVES:
Explore the 1
st
trimester (TM) maternal plasma proteome in relation to systolic (S) and diastolic (D) BP in the 1
st
and 3
rd
third TM, and 3 months postpartum.

METHODS:
We obtained baseline, 1
st
TM plasma samples from n=435 women from an antenatal multiple micronutrient vs iron-folic acid supplement trial in rural NW Bangladesh (West et al JAMA 2014). Phlebotomy occurred
<
12 wk gestation. Blood pressure was measured (mmHg) by trained staff with manual sphygmomanometers. Plasma specimens were shipped to Baltimore under liquid nitrogen, stored for ~10 years at -80
o
C before processing by SomaScan
®
, a synthetic aptamter-based assay that quantified relative abundance of 6,431 unique plasma proteins. We performed simple linear regression to correlate (r) protein abundance with SBP and DBP at each timepoint, adjusting for maternal age, body mass index, parity, and trial supplement allocation, defining significance as a false discovery rate (chance-corrected p-value, q) of q
<
0.05.

RESULTS:
Six proteins (led by IGFBP-2, r=-0.22 and leptin, r=0.21), 2 proteins (NRP1, r=-0.22 and APOE, r=0.21) were correlated with 1
st
trimester, and 4 (LPLC1, APOF, OMGP, SLAF9) and zero proteins with 3
rd
trimester SBP and DBP, respectively (q
<
0.05). In contrast, 41 proteins were associated with both SBP and DBP at 3-month postpartum, 39 of which overlapped, of which 37 were positively correlated (ranges: r=0.62-0.17) (Figure1A and B). Proteins postpartum were different from 1
st
trimester. These included proteins involved in transcription (ex: CREBZF, GALNT2), cell proliferation (HMGN3, CUZD1), vascular function (UBE2H, EDN2), and inflammation (LIRA2).

CONCLUSIONS:
Findings suggest that the maternal plasma proteome from the 1
st
TM is most aligned with cardiovascular tensive physiology of a non-pregnant (i.e., postpartum) person. BP during pregnancy itself (i.e. first and third TMs) may not follow the same pathways regulating it in the non-pregnant state (postpartum). The complex physiology of blood pressure regulation in pregnancy should be considered in studies exploring proteomics in pregnancy.
Abstract 4145409: Detection and Significance of Nonsustained Ventricular Tachycardia in a Post-stroke Population
Authors: Rekapalli Pranav , Oraii Alireza , Dixit Sanjay , Epstein Andrew , Frankel David , Hyman Matthew , Lin David , Markman Timothy , Messe Steven , Nazarian Saman , Schaller Robert , See Vincent , Yang Wei , Kasner Scott , Marchlinski Francis , Deo Rajat
Published: November 2024

Introduction / Background:
Clinical guidelines emphasize cardiac rhythm monitoring in post-stroke patients (pts) for detecting atrial fibrillation. Limited studies have evaluated other arrhythmias in this population.

Objective:
We sought to assess the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in pts who have had an ischemic stroke or TIA. We hypothesize that pts who have NSVT will have a higher risk of cardiovascular events and recurrent stroke than those who do not have NSVT on monitoring.

Methods:
In a large, quaternary academic health system, we evaluated 563 consecutive, post-stroke pts, who did not have a history of MI or heart failure (HF) and underwent routine, mobile cardiac outpatient monitoring (MCOT, Phillips Biotelemetry, Malvern, PA) between 2019 and 2023. We evaluated all episodes of NSVT, defined as a ventricular rhythm with a wide QRS complex for at least 3 beats and a rate faster than 100 beats per minute. We collected all NSVT episodes during the wear period. For each episode, we also collected the total duration and maximum heart rate. We also calculated the NSVT burden by summing the duration of NSVT episodes and dividing by the total monitoring time. The electronic health record was utilized to identify incident MI, heart failure and/or recurrent stroke. Cox proportional hazard models were used to determine the risk of developing a cardiovascular event across the follow-up period.

Results:
Of 563 patients, the mean duration of MCOT monitoring was 19±7 days. NSVT was observed in 113 pts (mean 1.8±2.5 episodes per patient). Compared to pts who did not have NSVT, those with NSVT were older, more likely to be male, and more likely to smoke. No differences were observed in the prevalence of hypertension, diabetes, or hyperlipidemia. After a median follow-up of 920 days [IQR 844], there were 123 cardiovascular events. Patients with NSVT had higher risk of incident HF (HR 4.7, 95% CI [1.8, 12.1]; p = 0.002), incident MI (HR 4.2, 95% CI [1.8, 10.0]; p = 0.001) or recurrent stroke (HR 2.1, 95% CI [1.2, 3.7]; p = 0.007). Among those with NSVT, a higher NSVT burden was associated with a greater risk of cardiovascular events (p=0.004).

Conclusion:
In post-stroke patients, the presence and burden of NSVT are associated with a higher risk of incident cardiovascular events and recurrent stroke. Future studies should evaluate whether NSVT is a modifiable marker of cardiovascular risk in these pts.
Abstract 4145545: Mortality and Ventricular Support Use in Cardiogenic Shock between 2018-2023: A Report from the Northern New England Cardiovascular Disease Study Group
Authors: Devries James , Gupta Tanush , Ross Cathy , Rashid Khaldoon , Hassan Ansar , Chaudry Hannah , LAHOUD Rony , Lin Isabelle , Rothstein Eric , Young Michael
Published: November 2024

Background:
Mortality from cardiogenic shock remains high, despite increasing awareness and multiple national initiatives to improve survival. Little is known about the relationship between support device use and overall survival in patients with cardiogenic shock. We sought to examine the temporal trends in mortality and ventricular support in patients with cardiogenic shock undergoing PCI in Northern New England.

Methods:
The NNE registry was queried to identify patients presenting for PCI who manifest cardiogenic shock between 2018 and 2023. Shock was defined by the NCDR definition including sustained hypotension requiring ionopressor use. Demographics, procedural data, mortality and intraprocedural ventricular support device use was collected. Standard statistical methods were used to calculate outcomes and statistical significance.

Results:
At total of 842 patients were identified who presented with shock. Overall in-hospital mortality was 30.9%, and varied from 27.4% in 2018 to 38.3% in 2021 during the height of the COVID-19 pandemic (Image 1). Mechanical support use remained flat, with an average use of 57% of all cases (Image 2). The distribution of intra-aortic balloon pumps and Impella devices changed, with Impella use increasing from around 41% in 2018 to 44%and IABP use decreasing from 55% to around 49% by the end of the study in 2023 (Image 3). There was no correlation between survival and type of mechanical support device used.

Conclusions:
Despite using ventricular support in nearly 60% of cases, in-hospital mortality for cardiogenic shock remains high at around 30%. A trend towards less IABP use and higher Impella use has not changed overall mortality. More study is needed to better understand how to optimize care for patients presenting with cardiogenic shock.
Abstract 4145579: Comparing 1-Year and 3-Year Outcomes of Atrial Fibrillation Ablation
Authors: Srivastava Viren , Deb Brototo , Chang Hui Ju , Ganesan Prasanth , Brennan Kelly , Feng Ruibin , Rogers Albert , Baykaner Tina , Wang Paul , Clopton Paul , Brodt Chad , Narayan Sanjiv
Published: November 2024

Background:
A major challenge in improving atrial fibrillation (AF) ablation is understanding variability in patient’s response to ablation. While some are long-term responders, others recur within a month. Some of this variability may be attributed to progression of AF despite short-term success manifested by acute termination. Our objective was to use our rich clinical database to identify predictors of differential response to ablation.

Method:
We studied 597 consecutive patients with drug-refractory AF, enrolled prospectively for a uniform AF ablation strategy at Stanford Health. We applied logistic regression to 73 clinical variables to identify features associated with freedom from AF or atrial tachycardia (AT) at 1-3 years.

Results:
Patients (N=597) were 65.4±10.4 years, 29.0% female, BMI 29.6 kg/m2, 60.1% with non-paroxysmal AF, and 68.8% at de novo ablation. N=253 (42.4%) recurred at 1 year, N=101 (16.9%) within 1-3 years, and N=243 (40.7%) were free of AF beyond 36 months. One year success in adjusted analyses was associated with fatigue, prior ablation, PVI approach, beta-blocker usage, digoxin usage, and GDMT usage. AF progression at 3 years was associated in adjusted analyses with post-ablation asthma and post-ablation usage of direct oral anticoagulants. In addition, pre-ablation stroke and presenting rhythm was associated with both outcomes.

Conclusion:
In a large prospective AF registry, we identified features which differed between patients with 1-year success and 3-year success, as well as factors shared between endpoints. This data may provide mechanistic insights and help to guide and personalize ablation.
Abstract 4145605: Disease-Causing Variants in Genes Associated with RASopathy and Aortopathy in Advanced Dilated Cardiomyopathy
Authors: Cao Louie , Rushakoff Joshua , Williamson Ian , Karlstaedt Anja , Kittleson Michelle , Czer Lawrence , Kransdorf Evan
Published: November 2024

Introduction:
Genetic testing reveals the presence of disease-causing (American College of Genetics and Genomics [ACMG] likely pathogenic [LP] or pathogenic [P]) variants in about 20% of patients with dilated cardiomyopathy (DCM). Exome sequencing can identify variants in novel genes that may be associated with DCM.

Research Question:
Do patients with advanced DCM harbor LP/P variants in genes associated with non-dilated cardiac, muscular, or vascular phenotypes?

Goals:
We determined the prevalence of LP/P variants in genes associated with 3 non-dilated cardiac, 1 muscular, and 1 vascular phenotype in 60 patients with advanced DCM requiring heart transplant.

Methods:
We conducted a retrospective study of patients who received a heart transplant between 2017 and 2023 at Cedars Sinai and who provided informed consent to participate. All subjects had DCM defined by LVEF ≤ 50% and LVEDD ≥ 95
th
percentile for sex and height. Whole exome sequencing was performed on explanted heart tissue. We assessed for rare variants in genes classified as having definite, strong, or moderate association with DCM, hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), RASopathy, muscular dystrophy (MD), and thoracic aortic aneurysm (TAA) by ClinGen Gene-Disease Validity Curation Expert Panels. Variant pathogenicity was determined using ACMG criteria.

Results:
We identified 13 patients (22%) with LP/P variants in DCM genes. For non-DCM genes, we identified 12 LP/P variants in a total of 11 patients (18%) (FIGURE). There were no variants in HCM or ARVC genes. We identified 5 patients each with 1 LP/P variant in RASopathy genes; of these, 2 were in conjunction with DCM variants. We identified 2 patients each with 1 LP/P variant in MD genes. We identified 5 patients with LP/P variants in TAA genes; of these, 2 were in conjunction with a single DCM variant. No patients carrying RASopathy, MD, or TAA LP/P variants exhibited non-cardiac phenotypic manifestations of these conditions.

Conclusion:
In patients with advanced DCM requiring heart transplant, we found that 18% of patients harbored LP/P variants in genes associated with RASopathy, MD, or TAA, without exhibiting non-cardiac phenotypic manifestations of these conditions. Further research is needed to validate these gene variants as primary or secondary causes of DCM. If validated, more expansive genetic testing may be indicated in patients with advanced DCM.
Abstract 4145655: Association Between Social Vulnerability Index and Heart Failure Mortality in the USA
Authors: Gonzalez Laura , TABOWEI GODFREY , Twayana Anu Radha , Lodhi Shahmeer , Al-Ayyubi Rami
Published: November 2024

Background:
Heart failure (HF) is a primary cause of hospital readmissions with extremely high projected annual costs. Social Vulnerability Index (SVI) assesses a community's ability to recover from external impacts on public health and provides valuable insights into community-level health outcomes. We aim to identify the association between SVI and HF.

Methods:
We used a national database (CDC WONDER) to identify the mortality of HF patients in the USA who were ≥25 years in 2020. HF was identified by specific ICD codes I11.0, 13.0, I13.2, and I50. We obtained the SVI per county from the CDC Database. We used the Pearson correlation coefficient (PCC) to examine the association between HF mortality and total SVI overall and within subgroups. Additionally, we employed ANOVA to evaluate the relationship between SVI quartiles and mortality.

Results:
In 2020, out of 215,907,184 individuals, 113,401 died of HF (40.7% were female and 37% male, 65.9% were of white race, and 8.8% Hispanic). Age-adjusted mortality rate (AAMR) was higher in males (65.3 vs 50.7 in females) and in Black race (75.8 vs 55.8 in White). However, the AAMR was lower in Hispanics (33.5 vs 58.6). Mortality rate increased from 0.044% in 2016 to 0.052% in 2020. The SVI ranged from 2.6045 to 12.7688. Texas, Mississippi, and Georgia were the states with the most counties in the 4th quartile of the SVI. In 2020, Mississippi, Alabama, and Louisiana had the highest AAMR (94.9, 88.6 and 76.4). A weak positive linear relationship was observed between HF mortality and total SVI, with a PCC of 0.2546, p <0.001. When divided into groups, socioeconomic status showed a moderate positive linear relationship, while household showed a weakly positive relationship, with PCC values of 0.32 and 0.27, respectively. For racial and ethnic minorities and house and transportation type, there was a very weak positive relationship (PCC 0.03 and 0.04), not statistically significant. The rate of change of mortality from 2016 to 2020 also had a weak positive linear relationship with SVI (PCC 0.13, p <0.001). When ANOVA was applied, the F-statistic was 24.1 (p <0.001), indicating significant variation between the SVI quartiles, especially for quartile 4.

Conclusion:
There is a positive association between SVI and HF mortality rates. Counties with greater social vulnerability experience higher mortality rates from HF, suggesting that targeted public health interventions in high-SVI areas could potentially improve outcomes.
Abstract 4145662: Mechanical Cardiac Support Reduces Frequent PVCs - Now That's a Stretch!
Authors: Saga Anusha , Agronin Jacob , Coulis Alexis , Deak Andrew , Cronin Edmond
Published: November 2024

Background:
Although ample evidence exists for the causative role of frequent premature ventricular complexes (PVCs) in the development of cardiomyopathy, they may also be found in cardiomyopathy of other causes. We describe a case of improved PVC burden following implantation of a temporary mechanical circulatory support device in a patient with advanced heart failure.

Case Description:
A 63-year-old male with familial non-ischemic cardiomyopathy and advanced heart failure on high dose milrinone (0.5 mg/kg/min) was admitted after outpatient right heart catheterization showed cardiogenic shock with high left ventricular (LV) filling pressures and cardiac index of 1.8 L/min/m2. On a previous admission, a high PVC burden had been noted but decreased markedly on outpatient ambulatory monitor placed on the day of discharge (Figure 1A). Telemetry was notable for a high PVC burden, predominated by bigeminy, with a predominant PVC morphology localized to the LV outflow tract (LVOT) (Figure 1B). The patient failed to improve with diuresis requiring axillary implantation of an Abiomed Impella 5.5 heart pump (Impella), with immediate improvement in cardiac output and pulmonary artery pressures. Preoperative transthoracic echocardiogram showed an LV end diastolic diameter (LVIDd) of 70mm compared to 65mm after Impella placement. Of significance, telemetry demonstrated a significantly lower PVC burden after Impella placement (Figure 1C).

Discussion:
Although frequent PVCs can cause or be the result of cardiomyopathy, data on the effect of volume overload on PVC burden, as demonstrated in this case, are lacking. Left ventricular unloading with mechanical cardiac support led to a dramatic and immediate drop in PVC burden. We suggest that Impella placement relieved congestion and therefore LV stretch, reducing the excitability of the LVOT. This novel observation implies that PVC burden should be assessed when patients are euvolemic and warrants further exploration of the relationship between LV congestion and PVCs.
Abstract 4145930: Heart Failure with Preserved Global Longitudinal Strain: A Distinct Phenotype in Patients with Preserved Ejection Fraction: Data from A Real-World Registry
Authors: Kim Gi Rim , Kim Kyu , Gwak Seo-Yeon , Lee Hyun-Jung , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: November 2024

Background:
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome caused by various pathophysiologic mechanisms, and has recently received increasing attention. Many research results show that the longitudinal left ventricular (LV) function is deteriorated, however, in the real world, we often encounter patients with preserved LV global longitudinal strain (GLS). This study sought to determine the prevalence, characteristics, and outcome of patients with preserved LV GLS in a real-world registry of HFpEF.

Method:
The registry data included 1,798 patients with HFpEF (72.2 ± 11.6 years, 55.2% female) who met the inclusion criteria of previous randomized controlled trials (New York Heart Association class II or higher symptoms, LVEF > 40%, and NT-proBNP > 300 pg/mL) at a single tertiary hospital between 2014 and 2021. LV GLS analysis was performed using vendor-independent 2D speckle-tracking imaging software (
TomTec
;
Image Arena
4.6, Munich, Germany). Patients with LV GLS ≤ -18% were defined as heart failure with preserved GLS. The primary outcome was a composite of heart failure admissions and cardiovascular death.

Results:
In this population, 757 (42.1%) patients had preserved LV GLS. The patients with preserved GLS were tended to be younger (71.7 ± 11.5 vs. 72.7 ± 11.6 years, p=0.073) and more female predominance (60.6 vs. 51.3%, p<0.001), and wider pulse pressure (61.0 ± 17.4 vs. 54.8 ± 18.1 mmHg, p<0.001) compared with those with reduced GLS. The average NT-pro BNP of the preserved GLS group was 2242.4 ± 4391.8 pg/ml and the average LV GLS was -20.1±1.6%, which were significantly lower than each value of the reduced GLS group. In terms of echocardiographic characteristics, the patients with preserved GLS had higher LV ejection fraction (68.8 ± 5.8 vs. 62.5 ± 8.6%, p<0.001) and stroke volume (78.1 ± 21.4 vs. 61.9 ± 19.3, p<0.001). During 21.3 months (interquartile range 6.6-39.7 months) follow-up, the group with preserved GLS had a better primary outcome than the group with reduced GLS (log-rank p < 0.001)
(Figure)

Conclusion:
Heart failure with preserved GLS is common among patients with HFpEF in real-world data. This phenotype is more common in females, is associated with higher stroke volume and arterial stiffness, and ultimately shows a favorable outcome.
Abstract 4145942: A hepatic steatosis-mediated metabolite reprograms macrophage lipid metabolism and aggravates atherosclerosis
Authors: Long Ting , Feng Ruijia , Feng Weiqi , Peng Guiyan , Yang Wenchao , Li Zilun , Huang Kan , Chang Guangqi
Published: November 2024

Background:
Atherosclerotic cardiovascular disease (ASCVD) stands as the foremost cause of mortality and disability among adults worldwide. Despite non-alcoholic fatty liver disease (NAFLD) has been well-characterized as an independent risk factor of atherosclerosis (AS), the precise underlying mechanisms remain poorly elucidated. We recently identified N-methyl-2-pyridone-5-carboxamide (2PY), the main end product of nicotinamide in human, as a pro-steatotic metabolite markedly elevated in hepatic steatosis conditions. The pathological increase in plasma 2PY levels has been intricately linked to an escalated susceptibility to cardiovascular issues.

Research Questions:
We hypothesized that 2PY might be a potential mediator bridging the association between NAFLD and the progression of AS.

Goals:
To elucidate the role and mechanistic insights of 2PY in the crosslink between hepatic steatosis and AS.

Methods:
Mass spectrometry was conducted to determine the plasma levels of 2PY in Apolipoprotein E-deficient (ApoE-/-) mice. Five-week-old male ApoE-/- mice fed a standard laboratory diet (SLD) or a western diet (WD) were intraperitoneally injected with 2PY or its vehicle for 10 weeks. Parameters of systemic metabolism, hepatic steatosis and AS were evaluated. Human THP-1 macrophages were used to investigate the effect of 2PY on oleic acid-induced foam cell formation. Lipidomic and transcriptomic analysis were performed to identify the alterations of lipids and genes in THP-1 macrophages upon 2PY treatment.

Results:
The expression of hepatic aldehyde oxidase 1, a key metabolic enzyme involved in 2PY metabolism, showed upregulation in the steatotic liver, resulting in the excess 2PY in WD-induced ApoE-/- mice. The plasma concentration of 2PY directly correlated with plaque area and lipid deposition in mice aortas. Furthermore, our study demonstrated that administration of 2PY aggravated lipid metabolic dysbiosis, hepatic steatosis and AS progression in mice fed either a SLD or a WD. In vitro, supplementation of 2PY dose-dependently increased intracellular lipid content in THP-1 macrophages. Mechanistically, 2PY upregulated ELOVL Fatty Acid Elongase 6 (ELOVL6) expression and induced lipid metabolic reprogram in macrophages, thereby facilitating foam cell formation.

Conclusion:
Our study indicates 2PY as a pro-atherogenic metabolite that mediates the association between NAFLD and elevated ASCVD risk, thus providing mechanistic insight into the pathogenesis of AS.
Abstract 4145944: Disparities in Cardiovascular Multimorbidity and Mortality among Dual Medicare-Medicaid Beneficiaries: A Nationwide Cohort Study of >2 Million Patients
Authors: Lusk Jay , Kalapura Cheryl , Mentz Robert , Greene Stephen , Hammill Bradley , Mac Grory Brian , Li Fan , Xian Ying , Obrien Emily
Published: November 2024

Introduction/Background:
Patients dually eligible for Medicare and Medicaid have higher mortality rates and disparate outcomes for acute cardiovascular conditions. However, the association between dual eligibility and cardiovascular multimorbidity and associated mortality is not well-established.

Goals/Aims:
To understand differences in cardiovascular disease (CVD) outcomes among patients dually eligible for Medicaid and Medicare.

Methods/Approach:
We analyzed Medicare claims data from a 5% random sample of fee-for-service beneficiaries (2010-2019). The exposure was Medicaid dual eligibility. The primary outcomes were the development of incident cardiovascular disease or cardiovascular multimorbidity (defined as >=2 of the following conditions: stroke/TIA, myocardial infarction, atrial fibrillation, heart failure, and ischemic heart disease). The secondary outcome was death. Multistate survival models were used to estimate hazards of progression from no CVD to incident CVD, CVD multimorbidity, and death before and after adjustment for demographics and medical comorbidity burden defined using a 1-year lookback window.

Results/Data:
In total, 2,189,382 patients (12.9% dual-eligible for Medicaid) were included. Compared with non-dual eligible beneficiaries, dual-eligible beneficiaries were more likely to have at least one cardiovascular condition at baseline (23.6% vs. 15.0%). Over a median 5 years of follow-up, dual-eligible beneficiaries spent approximately 1 less year alive and free from CVD than non-dual eligible beneficiaries (4.89 years vs. 5.95 years). Dual-eligible beneficiaries were more likely to develop CVD and multimorbidity and had higher mortality rates before and after adjustment (Table 1 and Figure 2).

Conclusions:
Dual-eligible beneficiaries had higher rates of incident CVD, cardiovascular multimorbidity and associated mortality, illuminating the critical need for primary and secondary prevention of CVD in this vulnerable population.
Abstract 4145947: New Perspective on Guideline-Based Management of Atrial Fibrillation According to Socioeconomic Disparity
Authors: Kim Yeji , Seo Chang-Ok , Jeong Joo Hee , Lee Hyoung Seok , Shim Jaemin , Kim Young-Hoon , Choi Jong-Il
Published: November 2024

Background:
As the global incidence of atrial fibrillation (AF) increases, the importance of implementing GDMT (Guideline-Directed Medical Therapy) for managing AF is being emphasized.

Research Questions:
Applying guidelines universally across all countries and situations is realistically challenging.

Aims:
Identifying the appropriate income level for GDMT and highlighting the need for new standards.

Methods:
Based on data from the Global Burden of Disease 2021 and provided by WHO and the World Bank, information from 186 countries was analyzed. GDP was based on 2021 United states dollar (USD), and the average cost of AF treatment was analyzed in correlation with GDP and OOPs (Out-of-pocket Expenses) across four income groups. The percentage of the average cost paid by an individual for AF out of total OOPs was calculated as (Estimated patient payment based on previous studies x prevalence) x 100 / OOPs.

Results:
Among the 186 countries, the average GDPs of 58 HICs (High-Income Countries), 52 UMICs (Upper Middle-Income Countries), 54 LMICs (Lower Middle-Income Countries), and 22 LICs (Low-Income Countries) were studied. The prevalence of AF in HICs, UMICs, and LMICs showed a trend of increasing with income level, with age-standardized rates per 100,000 being 645.6 ± 164.0, 613.9 ± 100.3, and 528.3 ± 105.7 respectively. However, the rate of AF-related deaths was 5.6 ± 1.7, 5.5 ± 2.0, and 4.6 ± 1.3 (age-standardized rates per 100,000) respectively, with the proportion of AF deaths relative to prevalence being highest in UMICs, and higher in LMICs compared to HICs. In terms of rhythm control strategy, the specific cost of catheter ablation (22,143.5, by 2021USD) was affordable primarily in HICs, and the majority of LMICs showed a GDP lower than the AAD-only specific cost (7,622.7 by 2020USD), indicating economic barriers to GDMT for AF. The proportion of AF cost in OOPs showed a tendency to increase as the income level decreased.

Conclusion:
In the AF management, catheter ablation is considered viable only for a very small part of UMICs and primarily for HICs. In LMICs and most UMICs, the importance of medication-based therapy is highlighted, suggesting the need to establish new guidelines according to socioeconomic status.
Abstract 4145951: Mortality in Cardiac Amyloidosis: A Systematic Review and Meta-Analysis
Authors: Jha Mayank , Harikrishna Arya , Al Hooti Jubran , Saad Ur Rehman Muhammad , Jain Hritvik , Mal Madho , Haider Mobeen , Hotwani Priya , Tummala Nayanika , Aamir Muhammad , Rajeswaran Yasotha
Published: November 2024

Background:
Cardiac amyloidosis is an underdiagnosed cause of heart failure. The mean survival rate without treatment is low, signifying the importance of early diagnosis. The prognosis depends on the time of diagnosis and the severity of the disease before recognition and treatment. We performed a systematic review to evaluate patient characteristics and mortality in individuals with cardiac amyloidosis.

Methods:
PubMed, Scopus and Cochrane were systematically searched from the database inception to May 2024 to evaluate for mortality outcomes in patients with cardiac amyloidosis. The statistical analysis was performed using R-Studio software, and proportions with 95% confidence intervals (CI) were calculated using a random-effects model. The Kaplan Meier survival plots was also plotted for eligible studies.

Results:
Eighteen studies involving 7,268 patients were included. Patients with cardiac amyloidosis mostly presented with dyspnea and peripheral edema. Among the electrocardiographic abnormalities, atrial fibrillation was observed in 31.1% of patients, whereas atrioventricular block was observed in 6.2% of patients. Furthermore, 37.2% of patients experienced heart failure, 36.3% experienced reduced ejection fraction, and 3.2% of patients experienced cardiogenic shock. Majority of the patients were found to have an increase in left ventricular wall thickness (77.8%). The mortality associated with cardiac amyloidosis varied from 0% to 100%, with a summary estimate rate of 54% (95% CI: 31% to 77%). The median survival rate for 50% patients was around 2 weeks, which declined significantly over the next one week resulting into the cumulative survival of over only 21 days.

Conclusion:
Our results highlight the importance of considering cardiac amyloidosis in the differential diagnosis of all patients with heart failure or non-ischemic cardiomyopathy, particularly when there is an increase in ventricular wall thickness. Our review revealed a high mortality rate associated with cardiac amyloidosis. Early diagnosis and better therapeutic modalities have the potential to improve patient outcomes and reduce mortality rates.
Abstract 4146002: Advancing Cardiac Function Assessment with a Real-Time, Lightweight Deep Learning Network for Precise Left Ventricular Internal Diameter Measurement
Authors: Red Teddy , Tian Chao
Published: November 2024

The purpose of this study is to develop a real-time, lightweight deep learning network to accurately detect the Left Ventricular Internal Diameter (LVID) for enhanced precision and efficiency in cardiac function assessment.

Our approach redefines the task of locating LVID endpoints by framing it as a classification problem along two axes, thereby significantly reducing the computational burden. This novel approach ensures high accuracy and enables real-time deployment in clinical settings.

We conducted extensive training using EchoNet-LVH, a primary dataset comprising 12,000 meticulously labeled echocardiogram videos sourced from diverse patients exhibiting various cardiac conditions. Furthermore, we evaluated our model on two external datasets and collected specialized datasets to assess its generalizability: a pediatric dataset consisting of 892 key frames from 138 children to evaluate accuracy in young patients with distinct cardiac dynamics, and an adult dataset encompassing 298 key frames from 39 adults representing a wide range of cardiac health statuses for testing effectiveness across diverse demographics. On the EchoNet-LVH dataset, the model exhibited exceptional accuracy by achieving a mean absolute error (MAE) of 2.39mm and a mean absolute percentage error (MAPE) of 6.5%, thereby establishing a new benchmark for precision in left ventricular internal diameter (LVID) measurement. Notably, the model also demonstrated excellent generalizability across diverse patient populations in external datasets, yielding MAPEs of 6.4% in the pediatric dataset and 5.6% in the adult dataset. Moreover, its efficiency was underscored by an impressive forward inference speed of up to 401.82 FPS on advanced GPU, representing a substantial improvement over previous approaches. This accelerated processing capability enables real-time analysis, which is crucial for clinical applications as it facilitates immediate diagnostic feedback essential for effective patient management and care.

The proposed model significantly enhances the efficiency of LVID measurements while maintaining a high level of precision, enabling real-time and automated assessments of cardiac function that are highly suitable for clinical application.

In addition, its robust performance suggests a strong potential for widespread adoption in routine cardiac evaluations. Our approach provides rapid, accurate assessments of LVID makes it an invaluable tool for cardiac function evaluation.