bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4145015: BRASH Syndrome: A Rare But Rapidly Reversible Cause of Cardiogenic Shock
Authors: Imburgio Steven , Patel Palak , Alshami Abbas , Almendral Jesus , Apolito Renato , Schoenfeld Mattthew , Selan Jeffrey , Sealove Brett
Published: November 2024

Case Presentation:
A 98-year-old female with hypertension, atrial fibrillation on Metoprolol succinate 100 mg daily, and stage 3a chronic kidney disease presented to the emergency department with altered mental status. On arrival, her heart rate was 30 BPM and blood pressure was 79/47 mmHg. Physical examination revealed lethargy, bradycardia, and cool extremities. An electrocardiogram showed junctional bradycardia at 36 BPM with a known right bundle branch block. Laboratory tests indicated shock with elevated lactic acid (2.6 mmol/L), creatinine (1.71 mg/dL from a baseline of ~1.20 mg/dL), transaminitis (aspartate transaminase 68 U/L, alanine transaminase 79 U/L), and hyperkalemia (potassium 6.1 mmol/L). The diagnosis of BRASH syndrome was made based on bradycardia, renal dysfunction, AV nodal blockade, shock, and hyperkalemia. Due to concerns of cardiogenic shock resulting from profound bradycardia, an intravenous dopamine infusion was initiated, and the patient was transferred to the cardiac critical care unit. She responded to medical management addressing hyperkalemia and bradycardia, and did not require renal replacement therapy or pacemaker placement. Following these interventions, her mental status, vital signs, and signs of end-organ damage rapidly improved. The patient was downgraded and subsequently discharged with close cardiology follow-up.

Discussion:
This case highlights the under-recognized diagnosis of BRASH syndrome as a cause of cardiogenic shock. BRASH syndrome, an acronym for Bradycardia, Renal failure, AV node blockers, Shock, and Hyperkalemia, is typically observed in patients on AV nodal blocking medications. The proposed pathophysiology involves an acute kidney injury, often precipitated by dehydration in elderly patients with preexisting kidney disease. The renal impairment leads to hyperkalemia and accumulation of AV nodal blocking medications like beta-blockers, which act synergistically to produce significant bradycardia. This results in substantial cardiac shock, further worsening renal perfusion and fueling a vicious cycle. Clinicians should recognize the combination of features rather than focusing solely on individual components of the syndrome. Immediate recognition and initiation of advanced measures such as inotropic support can reverse the underlying disease process and lead to a promising recovery. BRASH syndrome, though rare, is a rapidly reversible cause of cardiogenic shock if promptly identified and managed.
Abstract 4145037: Effects of Empagliflozin on cardio-renal interaction in heart failure: Results from the CINNAMON-study and in-vivo experiments
Authors: Sinha Frederick , Klatt Susanne , Rietmann Alexander , Schoepperl Anna , Born Sebastian , Maier Lars , Schweda Frank , Wagner Stefan
Published: November 2024

Background and Purpose:
Heart failure is associated with renal dysfunction suggesting a pathophysiological link between heart and kidney. Empagliflozin, a SGLT2 inhibitor, showed beneficial effects on both cardiovascular and renal endpoints. However, mechanistically, it is unclear if empagliflozin-dependent kidney protection is mediated via inhibition of tubular SGLT2 or more indirectly via improved cardiac function.

We hypothesized that Empagliflozin treatment improves left ventricular ejection fraction (LVEF) and thereby renal function in patients and mice independent of renal SGLT2 inhibition.

Methods:
We evaluated LVEF and GFR in our patients with HF with reduced (n=32) and preserved ejection fraction (n=59) after 30 and 180 days (prospective, single-arm CINNAMON-study, DRKS00031101). Furthermore, we conducted transverse aortic constriction (TAC) in C57BL/6J (wildtype, WT) and SGLT2 deficient mice (SGLT2-KO). Animals received either Empagliflozin (10 mg/kg bw) or vehicle. Cardiac function was evaluated by echocardiography and kidney function by FITC-Sinistrin measurement (GFR).

Results:
Empagliflozin treatment improved LVEF in patients with reduced LVEF whereas in patients with preserved LVEF (Fig. A, B) there was no change in LVEF (Fig. C). Interestingly, only in patients with LVEF < 40% there was a parallel improvement in GFR (Fig. D, E), whereas in patients with LVEF > 40% we only observed the well-known transient drop of GFR (Fig. F).

In mice after 10 weeks, echocardiography confirmed TAC induced pressure-overload, leading to reduced LVEF, which was attenuated by EMPA (Fig. G). Interestingly, at 10 weeks, TAC also reduced GFR, which was prevented by EMPA (Fig. H). To test if direct inhibition of SGLT2 is mechanistically involved, TAC surgery was repeated in SGLT2-deficient mice (SGLT2-KO). In fact, exposure to TAC resulted in comparable reduction of LVEF in SGLT2-KO and EMPA prevented this deterioration similar to WT mice (Fig. G vs. I). Surprisingly, EMPA also prevented GFR deterioration 10 weeks after TAC in SGLT2-KO mice with comparable magnitude as in WT mice (Fig. J), suggesting that the reno-protective effect of Empagliflozin was independent from SGLT2 inhibition.

Conclusion and Outlook:
This is the first study investigating the role of SGLT2 in Empagliflozin-dependent kidney protection in patients and of mice with heart failure. Importantly, Empagliflozin treatment prevented deterioration of LVEF and GFR independent of the presence of SGLT2.
Abstract 4145039: Prevalence, Penetrance, and Phenotypic Manifestation of Incidental Cardiomyopathy-Associated Genetic Variants in a Quaternary Medical Center-based Population
Authors: Figueiral Marta , Fazzini Luca , Tan-Arroyo Jennifer , Olson Rory , Bublitz Josh , Olson Janet , Klee Eric , Pereira Naveen
Published: November 2024

Background:
Cardiomyopathies (CM) are a leading cause of heart failure. Identification of genetic risk preemptively may allow detection of the earliest phenotypic manifestations through implementation of interval-based cardiac screening. Previous population-based genetic screening studies have limited follow-up and inadequate phenotyping.

Hypothesis:
Disease penetrance of CM variants is significantly higher than previously reported.

Aims:
To determine the prevalence, penetrance, and disease expression of incidental CM-related genetic variants in an unselected, richly phenotyped, adult population.

Methods:
We analyzed a random sample of 10,000 patients from a quaternary medical center-based biobank cohort for reportable variants in 22-cardiomyopathy genes. Prioritization of genetic variants was performed using Semi-Automated Variant Interpretation, a novel software that has been previously developed and validated at our center. Prioritized variants were then manually curated by 2 independent variant interpretation specialists. Clinical phenotypes and outcomes of participants with likely pathogenic/pathogenic (LP/P) variants were determined.

Results:
LP/P cardiomyopathy variants were present in 1% of our cohort (n=104) within the following genes:
TNNT2
(n=1),
DES
(n=2),
LMNA
(n=2),
MYL2
(n=2),
TNNI3
(n=2),
DSG
(n=4),
FLNC
(n=4),
DSC2
(n=6),
SCN5A
(n=7),
PKP2
(n=10),
DSP
(n=12),
MYH7
(n=14),
TTN
(n=17),
MYBPC3
(n=21). Only 1 participant carried two different LP/P variants. A definitive disease penetrance defined as heart failure or cardiomyopathy was found in 34% of genotype positive (G+) individuals. Possible disease penetrance defined as presence of structural heart disease identified by echocardiography was found in an additional 16% of participants (concentric left ventricular hypertrophy, diastolic dysfunction, biatrial and left atrial enlargement). Combined definitive and possible disease penetrance was found in 50% of G+ individuals. Arrhythmias and/or cardiac conduction disease (atrial fibrillation, atrioventricular block, ventricular arrhythmia) were present in 31% of G+ individuals.

Conclusion:
Cardiomyopathy associated LP/P variants are present in a small subset of a large quaternary medical center population as previously reported but unlike prior studies, disease penetrance manifesting as cardiac structural abnormalities and heart failure is high in G+ individuals.
Abstract 4145054: Artificial Intelligence-Enhanced Electrocardiogram Trajectories for Age Estimation: Prognostic Assessment and Differential Prediction of Atrial Fibrillation Occurrence
Authors: Hwang Taehyun , You Seng Chan , Kim Sangyeol , Eom Sujeong , Boo Dachung , Kim Subin , Kim Daehoon , Kim Tae-Hoon , Uhm Jae-Sun , Pak Hui-Nam , Lee Moon-Hyoung , Yu Hee Tae , JOUNG BOYOUNG
Published: November 2024

Background:
The use of Artificial Intelligence (AI) to estimate age from 12-lead electrocardiogram (ECG) data has shown promise as a biomarker for predicting future cardiac disease risk. However, the long-term outcomes based on the temporal variations in the AI-ECG age gap remain uncertain.

Hypothesis:
This study aims to longitudinally track the differences between AI-predicted age and actual chronological age using ECG data and evaluate whether significant clinical differences in atrial fibrillation (AF) occurrence exist among various patient groups.

Methods:
From a single-center cohort not previously used for AI-ECG age prediction (121,702 individuals, 522,261 ECGs), 5,317 individuals with 24,368 ECGs who had an initial ECG and a follow-up ECG in the fifth year, along with at least one intervening ECG, were included for analysis. The absolute age gap, defined as the absolute difference between ECG-predicted and chronological age, was constrained to ±10 years for this analysis. Latent class trajectory modeling was employed to categorize groups based on the AI-ECG age gap trajectories.

Results:
The analysis identified four distinct trajectory groups based on age gap patterns: Consistently Young ECG (28.7%), Reversed ECG Aging (35.5%), Accelerated ECG Aging (8.0%), and Consistently Old ECG (27.9%). Both the Accelerated ECG Aging group (adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.07-2.79, p-value = 0.025) and the Consistently Old ECG group (adjusted HR 1.78, 95% CI 1.27-2.49, p-value < 0.001) had a significantly higher cumulative incidence of AF compared to the Consistently Young ECG group. Four independent predictors of these trajectories were identified: baseline age, chronic kidney disease, diabetes mellitus, and hypertension.

Conclusion:
The study identified four distinct AI-ECG age gap trajectory groups, with the Accelerated ECG Aging and Consistently Old ECG groups showing a significantly increased risk of AF occurrence.
Abstract 4145068: Machine learning analysis of serum proteome in the diagnosis of COVID-19 myocarditis
Authors: Gordon Kyle , Gordon Cade William , Roman Ana , Watson Samuel , Tong Matthew , Addison Daniel , Jones Daniel , Oltz Eugene , Lozanski Gerard , Liu Shan-Lu , Daniels Curt , Rajpal Saurabh , Madiai Francesca , Gumina Richard
Published: November 2024

Background:
The COVID-19 global pandemic was the third leading cause of mortality in the US in 2020 and is associated with numerous complications, including myocarditis. Diagnosis of COVID-19 myocarditis can involve costly and invasive procedures. In addition, asymptomatic myocarditis could place people at risk for arrhythmias and sudden cardiac death.

Objective:
To use machine learning (ML) of serum proteomics to distinguish asymptomatic COVID-19 positive volunteers with and without myocarditis.

Approach and Results:
In 2020, for a cohort of 20 previously healthy 18–23-year-old individuals diagnosed with COVID-19 two weeks after the diagnosis, CMR was performed to assess for evidence of cardiac inflammation and serum samples were obtained the same day (10 were diagnosed as myocarditis positive and 10 negative) We performed proteomic analysis using the SomaScan proteomics assay from SomaLogic. The data were passed through an initial feature selection process of 1000 rounds of bootstrapped multivariate logistic regression using L1-regularization to introduce sparser feature utilization. The top 25 features (largest absolute log-odds) were utilized for a final logistic regression analysis. The feature selection step was optimized to have an average receiver operating characteristic area under the curve (ROCAUC) of 83.29% over 1000 iterations, but the final model utilizing only 25 proteins achieved an average ROCAUC of 99.58%. This method produced 22 proteins with significant odds-ratios for COVID-19 myocarditis (OR 95%CI excluding 1), of particular interest are those involved in inflammatory control and injury response mechanisms. Increases in the heat shock protein DNAJB11 (1.19 [1.10, 1.27]) and calponin-2 (1.17 [1.10, 1.25]), as well as decreases IL1RN (0.88 [0.83, 0.93]) were associated in increased likelihood of CMR diagnosed myocarditis (Fig 1A). Furthermore, a UMAP projection of the data using the 22 significant features yielded a clear visual distinction between those with and without COVID-19 myocarditis via CMR (Fig 1B).

Conclusion:

Utilizing ML on serum proteomic screenings of asymptomatic young COVID-19 patients, we can differentiate between those with CMR myocarditis positive and negative patients.
Abstract 4145081: ACUTE ISCHEMIC STROKE IN YOUNG CANNABIS USERS: A NATIONWIDE ANALYSIS
Authors: Joseph Varughese Vivek , Anil Peethambar Gowri , JAYARAJ RANJINI NIVED , Mummadisetty Anvitha
Published: November 2024

Background:
The incidence of stroke in young adults is on the rise in the United States. Drug abuse has been proposed as a known modifiable risk factor for stroke in this age group. The association between cannabis use and stroke in young adults is an area that needs further exploration.

Research Hypothesis:
Cannabis is an independent modifiable risk factor for stroke in young adults with Cannabis Use Disorder(CUD).

Aim:
To investigate the association between Cannabis Use Disorder(CUD) and Stroke in young adults.

Methods:
Using the National Inpatient Sample 2019, admissions for stroke in the age group of 18-45 were identified. The cohort was subdivided into admissions with documented CUD. Demographic data of the cohort was analyzed, including the prevalence of comorbid conditions. Using multivariate binomial logistic regression, the association between cannabis use and the occurrence of stroke was studied, after accounting for age, smoking, cocaine abuse, and uncontrolled hypertension(HTN). A two-tailed p-value <0.05 was used to determine statistical significance.

Results:
Out of the 13,514 stroke admissions identified, 1,027 (7.06%) had documented CUD. Analyzing the population, 63.87% were male, 39.57% were White, 38.5% were Black, and 12.3% were Hispanic. The prevalence of other comorbid conditions in this group included uncontrolled HTN (45.67%), alcohol abuse (15.78%), major depression (13.08%), COPD (11.56%), congestive heart failure (8.95%), and cocaine abuse (5.98%). [Table 1]

The crude odds ratio (OR) for stroke among admissions with CUD was 2.998 (95% CI: 2.587-3.473, p=0.000). Significant association with stroke was also found between documented cocaine abuse (OR: 1.604, 95%CI: 1.195-2.152), smoking (OR: 2.214, 95%CI: 1.374-3.569), and uncontrolled HTN (OR: 2.114, 95%CI: 1.959-2.281,). Using binomial logistic regression analysis, after adjusting for age, smoking, cocaine abuse, and uncontrolled hypertension, the association between stroke and cannabis use disorder remained significant: OR of 2.956 (95%CI: 2.541-3.440). [Table 2]

Further analyzing 543,445 admissions of individuals aged 18-45 with documented CUD, we identified the following as significant risk factors for the occurrence of stroke: Black race (OR: 1.556, 95%CI: 1.16-2.08), uncontrolled hypertension (OR: 5.222, 95%CI: 3.92-6.94), congestive heart failure (OR: 2.763, 95%CI: 1.67-4.55), and a history of myocardial infarction (OR: 2.346, 95%CI: 1.15-4.76). [Table 3]
Abstract 4145086: Determining the Prevalence of Genetic Cardiomyopathies in Non-Ischemic Cardiomyopathy Patients Undergoing Cardiac Positron Emission Tomography-Computed Tomography: A Single Institution Experience
Authors: Roberts Jacob , Salavati Ali , Krokhaleva Yuliya , Allen-Auerbach Martin , Hayase Justin , Wang Jessica , Vaseghi Marmar
Published: November 2024

Introduction:
Inflammatory cardiomyopathies such as sarcoidosis are associated with increased focal 18F-FDG uptake on cardiac positron emission tomography-computed tomography (PET-CT). It has been reported that patients with genetic cardiomyopathies with desmosomal mutations may also have abnormal cardiac PET scans. The incidence and type of genetic cardiomyopathies with abnormal cardiac PET imaging remains unclear.

Objective:
To determine the prevalence of genetic cardiomyopathies in patients with abnormal cardiac PET imaging.

Methods:
Data from patients who underwent cardiac PET imaging at our institution between 2018-2024 were analyzed. Those who completed genetic testing were further identified and evaluated for mutation variant type and imaging findings.

Results:
Of 605 patients with non-ischemic cardiomyopathy referred for cardiac PET scans, 67 (11%, mean age 51.8 ± 15.4 years, 69% male, mean LVEF 46.5 ± 15.1%) had undergone genetic testing. Of these, 21% (n = 14) had evidence of focal inflammation and 15% (n = 10) had indeterminate PET results with assessment of focal inflammatory findings limited by incomplete suppression of physiologic metabolism at the time of imaging. Of patients with focal inflammation, 36% (n = 5) tested positive for known pathogenic gene variants:
DSP
(n =1),
FLNC
(n = 1),
LMNA
(n = 1), and
MYH7
(n = 2). An additional 4 patients with evidence of focal inflammation had variants of uncertain significance (VUS). Among the 10 patients with indeterminate cardiac PET findings, 3 had pathogenic mutations:
DSP
(n = 1),
HFE
(n = 1), and
TTN
(n = 1). There was no difference in the cardiac PET imaging findings of patients with versus without genetic cardiomyopathies with regard to focality or location of FDG uptake.

Conclusion:
Pathogenic mutations beyond desmosomal gene variants can present with evidence of inflammation on cardiac PET. Genetic testing amongst non-ischemic cardiomyopathy patients with abnormal cardiac PET scans should be considered to evaluate for other etiologies beyond sarcoidosis.
Abstract 4145107: Latest Insights in Drug-Induced Kounis Syndrome: A Systematic Review 2024
Authors: Shiza Saher , Ong Kenneth , Suhagiya Gaurang , Nazar Tazeen , Ahmed Zahoor
Published: November 2024

Background:
Kounis syndrome (KS), also known as allergic myocardial infarction, is a rare but potentially life-threatening condition characterized by acute coronary syndrome in the setting of allergic reactions triggered by drugs, foods, vaccines, or environmental exposure. Our study provides an updated comprehensive insight into this patient cohort on a large scale.

Methods:
We conducted a systemic literature search in PubMed, EMBASE, and Google Scholar between 2018 and 2024, using MeSH terms and keywords for “Kounis syndrome”, “drug”, and allergy to identify the cases of drug-induced KS. Initial search yielded 325 articles. After excluding duplicates, review articles and irrelevant studies, we included only 51 articles reporting drug-induced KS.

Results:
Our study identified 51 patients of KS with a median age of 56 ± 14 years. Of those, 56.86% were female. The most frequently implicated drugs in KS were antimicrobials (37.25%), followed by iodinated contrast media (19.60%), NSAIDs (15.68%), and antineoplastics (9.80%). Of those, 64.70% of patients were diagnosed with KS-I, 13.72% with KS-II, and 21.56% with KS-III. Chest pain (94.1%), dyspnea (90.1%), and palpitations (60.78%) were predominant initial manifestations, and most cases (78.43%) were presented within 1st hour of drug ingestion. ST-segment changes (100%) were common ECG findings, and 64.70% of patients had elevated cardiac troponin. All patients had reduced left ventricular ejection fraction (LVEF) (<50%), with severe cardiomyopathy (EF< 30%) in 35.29%. 96.07% of patients were discharged after a median length of hospital stays (11 ± 2.91 days) (Figure 1).

Conclusion:
Although rare, KS is a life-threatening adverse event of drug-induced allergic reactions. KS is challenging to diagnose due to mixed clinical presentations of acute coronary syndrome and allergic reactions. KS should be included in the differential diagnosis of patients presenting with acute coronary syndrome without typical risk factors after drug-induced allergic reactions, especially antimicrobials. Early recognition and appropriate management are crucial for optimum outcomes.
Abstract 4145109: Disturbed Flow (d-flow)-induced Endothelial Senescence-Associated Stemness (SAS): Unveiling the Impact of CD38 and LATS1/2 Depletion on Atherothrombosis Development
Authors: Kotla Sivareddy , Ko Kyung Ae , Lee Jonghae , Osborn Abigail , Chen Weiqing , Samanthapudi Venkata Subrahman K , Pathania Rajneesh , Mejia Gilbert , Hoang Oanh , Ostos Mendoza Keila Carolina , Mariscal Reyes Karla Natalia , Chau Khanh , Burks Jared K , Schadler Keri , Wang Guangyu , Chini Eduardo , Martin James , LE NHAT TU , Abe Junichi
Published: November 2024

Background:
Atherosclerotic plaques, especially high-risk ones, form in blood vessel regions exposed to d-flow. EC dysfunction induced by d-flow likely contributes to plaque development. In contrast, regions with laminar flow (l-flow) are less susceptible to plaque formation. Although the Hippo pathway is implicated in mechano-transduction, the exact role and molecular mechanisms of LATS1/2 in response to d-flow remain incompletely understood.

Methods:
We employed endothelial cell (EC)-specific Lats1 and Lats2 knockout mice within a partial left carotid ligation (PLCL) model to simulate disturbed flow conditions. We characterized plaques using imaging mass cytometry (IMC) and sequential immunofluorescence via COMET
TM
.

Results:
We investigated the effects of d-flow on YAP activity and LATS1/2 expression. While both l-flow and d-flow activate YAP activity, only d-flow leads to decreased LATS1/2 expression. We induced Lats1/2 deletion in tamoxifen-inducible Lats1
-/-
/Lats2
-/-
EKO mice. Within 14 days, all mice (27/27) died due to severe systemic edema and increased vascular permeability. In Lats1
+/-
/Lats2
-/-
EKO mice (LATS1/2-EKO), we observed atherothrombotic lesions characterized by increased EC proliferation and a senescence-associated secretory phenotype (SASP)
in vivo
. Mechanistically, d-flow reduces LATS1/2 expression, leading to increased CD38 expression. CD38 triggers not only SASP, but also senescence-associated stemness (SAS) via NAD
+
depletion, dependent on Lamin A but independent of YAP. We also explored the relationship between CD38 and Ki67 in plaques in vivo. We calculated the logarithm of the Ki67:CD38 expression ratio at the single-cell level using IMC/COMET data. Based on the trimodal density distribution of this parameter, we found that in one group, CD38 and Ki67 were linearly co-expressed, and the percentage of LATS1/2-depleted cells in this group exceeded that of wild type (WT) cells, suggesting that CD38’s pro-proliferative effects dominate under LATS1/2 depletion conditions, despite its role in inducing senescence. Lastly, inhibiting CD38 mitigated d EC SAS/SASP, and atherothrombosis under LATS1/2 depletion conditions.

Conclusions:
Reduced LATS1/2-mediated CD38 expression in response to d-flow leads to an EC response marked by increased SASP/SAS, ultimately contributing to atherothrombosis. While this phenomenon is common in human advanced coronary atherosclerosis, it is not observed in commonly used mouse models of atherosclerosis.
Abstract 4145121: Impact of Mavacamten on blood pressure in Hypertrophic Obstructive Cardiomyopathy
Authors: Shehadeh Mohanad , Eid Fahad , Rahhal Alaa , Hanafi Amir , Eid Mohamed , baibhav bipul
Published: November 2024

Background:
Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic disorder characterized by thickened heart muscle and dynamic left ventricular outflow tract (LVOT) obstruction. Mavacamten (Camzyos) is a novel therapeutic agent targeting myocardial contractility. This study evaluates the impact of Mavacamten on blood pressure (BP) and other clinical parameters in HOCM patients over a 24-month period.

Methods:
A retrospective study was conducted on 40 HOCM patients initiated on Mavacamten, with follow-ups at 12 and 24 months. Blood pressure measurements (systolic BP [SBP] and diastolic BP [DBP]) were recorded at baseline, 12 months, and 24 months. Secondary outcomes included changes in LVOT obstruction at rest and with provocation, the New York Heart Association (NYHA) functional class, and left ventricular ejection fraction (LVEF).

Results:
The study population had a mean age of 67 ± 10 years, with 50% male. Baseline characteristics included a high prevalence of hypertension (78%), dyslipidemia (67%), and atrial fibrillation (31%). At 12 and 24 months, there were no significant changes in SBP (137 ± 18 mmHg to 139 ± 18 mmHg at 12 months, p=0.850, and to 132 ± 17 mmHg at 24 months, p=0.607) or DBP (78 ± 11 mmHg to 80 ± 10 mmHg at 12 months, p=0.409, and to 80 ± 10 mmHg at 24 months, p=0.468). However, significant reductions were observed in LVOT pressure gradients both at rest (48 ± 41 mmHg to 11 ± 15 mmHg at 12 months, p<0.001, and to 8 ± 13 mmHg at 24 months, p<0.001) and with provocation (89 ± 59 mmHg to 27 ± 32 mmHg at 12 months, p<0.001, and to 22 ± 28 mmHg at 24 months, p<0.001). NYHA class improved significantly, with a higher proportion of patients in class I (3% to 21% at 12 months, p=0.031, and to 27% at 24 months, p=0.016) and a reduction in class III patients (50% to 12% at 12 months, p<0.001, and to 10% at 24 months, p=0.002). LVEF decreased from 69 ± 6% to 64 ± 4% at 12 months (p<0.001) and remained at 64 ± 6% at 24 months (p<0.001).

Conclusion:
Mavacamten use in HOCM patients over 24 months demonstrated stability in blood pressure but significant improvements in LVOT obstruction, NYHA functional class, and a slight decrease in the LVEF.
Abstract 4145138: Use of Cardiac Magnetic Resonance Imaging to Assess Response to Oral Treprostinil Therapy in Pediatric Pulmonary Hypertension Patients
1
Authors: Gaviria Susana , Kollar Sarah , Loke Yue-Hin , Truong Uyen
Published: November 2024

Background:
Pulmonary hypertension (PH) contributes to significant morbidity and mortality in pediatric patients. Cardiac catheterization remains standard of care for diagnosis and serial monitoring in PH patients despite its significant risk of morbidity and mortality. Cardiac magnetic resonance (CMR) imaging provides critical information about the right ventricle (RV) and left ventricle (LV) and may have significant prognostic power. We aim to use CMR to demonstrate response to oral Treprostinil in pediatric PH patients.

Methods:
This is a retrospective, multi-center study of 9 PH patients who underwent a baseline CMR study, as well as a follow up study 24 weeks following transitioning to oral Treprostinil from intravenous/inhaled formulations. Feature-tracking (Qstrain, Medis) was performed on short/long-axis cines to assess RV global longitudinal strain (GLS), LV GLS, and LV global circumferentialstrain (GCS). Volumetric data and conventional functional parameters were also compared, pre and post initiation of oral Treprostinil therapy.

Results:
Eighteen CMR studies from 9 patients were analyzed. Average baseline RV ejection fraction (EF) was 48.1% compared to post therapy RV EF 51.9% (p = 0.188). Average baseline RV GLS was -20.5% compared to post therapy RV GLS -23.3% (p = 0.025), Figure 1. Overall, there was no significant difference in LV EF, LV GLS, and LV GCS after transitioning to oral therapy. Increased RV EF post initiation of oral Treprostinil therapy correlated with increased magnitude LV GCS (r = 0.701, p = 0.036), reflecting critical interventricular interaction in the disease process.

Conclusion:
Assessment of RV strain is more sensitive in detecting improvement in cardiac performance following initiation of oral Treprostinil in pediatric PH patients compared to ejection fraction. Future studies should focus on the development of novel CMR biomarkers in place of cardiac catheterization in assessing cardiac performance in PH patients.

1. This abstract was written by one of ISS investigators, Dr. Truong, who is using data from TDE-PH-206 (pediatric oral Treprostinil study) to investigate cMRI parameters.
Abstract 4145142: Enhancing Inpatient Mortality Prediction in TAVR Patients: A Modified CHA2DS2-VASc Approach Using Machine Learning
Authors: Haseeb Shahan , Munir Shafia , Ahmed Omair , Qureshi Muhammad Ahmad , Patel Himani , Gehres Eric , Siddiqui Taha , Zaman Muhammad , Ali Raiyan , Dwivedi Manu , Ansari Umair , Zulqarnain Muhammad
Published: November 2024

Introduction:
Inpatient mortality remains a significant concern for patients who have undergone transcatheter aortic valve replacement (TAVR) procedures. Accurate risk prediction models are vital for optimizing patient care and outcomes in this population. The CHA2DS2-VASc score has been utilized to predict various inpatient and long-term outcomes, irrespective of patient history of atrial fibrillation. This abstract introduces a novel approach to enhance inpatient mortality prediction in TAVR patients by adapting the CHA2DS2-VASc score using Lasso regression.

Methods:
We used the National Inpatient Sample Database to include all patients who underwent TAVR from 2018 to 2020. All patients with and without any history of atrial fibrillation or atrial flutter were included in the analysis. We employed Lasso regression, to modify the CHA2DS2-VASc score for predicting stroke risk in patients who underwent TAVR. The data was split into a 70:30 training-testing set. The model’s performance was evaluated using the Area Under the Receiver Operating Characteristic (AUROC) curve and compared to CHADS2-VASc.

Results:
The study included a total population of 28,684 patients in the training set and 12,290 patients in the testing set. The median age of the entire population was 80 years (IQR: 73-85), and females accounted for 44% of the total population. The mean CHA2DS2-VASc for the entire population was 3.82 (CI: 3.81-3.84) The AUROC values were 0.8239 for the training dataset and 0.8203 for the testing dataset, indicating strong discriminative ability in both cases. This performance was significantly improved compared to the CHA2DS2-VASc score (AUROC of 0.654).

Conclusion:
The modified CHA2DS2-VASc score improves inpatient mortality prediction for TAVR patients. With strong discrimination (AUROC 0.8239/0.8203) compared to the CHA2DS2-VASc score (AUROC 0.654), it holds promise for tailored risk assessment and improved patient care. Prospective validation is needed and comparison with the more widely used STS score is needed to establish real-world applicability.
Abstract 4145146: Familial Hypercholesterolemia With Concurrent Premature Coronary Artery Disease and Renal Artery Stenosis - A case report.
Authors: Prajapati Kesar , Desai Nisarg , Sailor Vikranti , Sahoo Sibasis
Published: November 2024

INTRODUCTION:
Familial Hypercholesterolemia (FH) is an underdiagnosed hereditary disorder of Low-density lipoprotein cholesterol (LDL-C) metabolism ,strongly associated with atherosclerotic cardiovascular disease (ASCVD). We present an FH case which shows the importance of early management.

CASE REPORT:
A 40 year old female with a history of Diabetes Mellitus, Hypertension (HTN), Non ST Elevation Myocardial Infarction (NSTEMI) came for angina like chest pain for 6 months. Her Coronary Angiography (CAG) showed Triple Vessel Coronary Artery Disease with 90% Left Main, 90% Left Anterior Descending, 80% Left Circumflex (LCX), 95% Right Coronary (RCA) arteries occlusion; Coronary Artery Bypass Grafting (CABG) was done. Her medical records showed poorly managed systolic blood pressure readings up to 180-200 mm Hg and hypercholesterolemia despite being on 3 antihypertensives and statins. On physical examination BMI 22 kg/m
2
, xanthelasmas, corneal arcus, elbow and achilles tendon xanthoma(figure.1),B/L Renal and carotid bruit was present. Her brother had premature CAD, daughters had hypercholesterolemia signs. Lab results indicated high cholesterol with, LDL 372.8 mg/dl; LDL/HDL 11.65. Multi-slice CT showed diffuse atheromatous changes of descending aorta, mesenteric arterial system and > 60% bilateral (L>R) renal artery stenosis(RAS). By Dutch Lipid Clinic Network criteria phenotypic FH was diagnosed and sent to lipid clinic for FH management.

DISCUSSION:
FH is an Autosomal Dominant disorder that leads to high LDL-C, escalating CAD risk by 20-fold. High intensity Statins cut LDL-C by 50%, pivotal in FH management. In our case late diagnosis of FH led to uncontrolled HTN due to RAS alongside CAD; Early diagnosis and medical management could have prevented the outcome as early initiation of statin in FH reduces their risk to age-matched population levels.

Conclusion:
FH is a systemic atherosclerosis often at subclinical level that needs to be investigated, also patients with premature ASCVD(male<55, female <60 years) and uncontrolled HTN with renovascular pathology should be screened for FH as early intense pharmacological management prevent serious atherosclerotic complications.
Abstract 4145167: Long-term Outcomes of Cardiogenic Shock and Cardiac Arrest Complicating ST-Elevation Myocardial Infarction According to Timing of Occurrence
Authors: KANHOUCHE GABRIEL , Nicolau Jose Carlos , Furtado Remo , Carvalho Luiz Sergio , Pileggi Brunna , Marchi Mauricio Felippi de Sa , Abi-Kair Pedro , Falcao Dalcoquio Talia , Lopes Neuza , Giraldez Roberto , Baracioli Luciano , GALEGO Felipe , Kalil Roberto , Abrahao Hajjar Ludhmila , de Brito Junior Fabio , Abizaid Alexandre , Ribeiro Henrique
Published: November 2024

Background:
Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence.

Objective:
This study sought to determine the incidence and the relationship between timing of occurrence and prognostic impact of CS and CA following STEMI in the long-term follow-up.

Methods:
We conducted a retrospective analysis of consecutive STEMI patients treated from 2004 to 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+ and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. The timing of their occurrence was evaluated according to initial cardiac catheterization as pre-, during- or post-procedure.

Results:
A total of 1,603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted HR 2.59 (95%CI 1.53-4.41), p<0.001, and HR 3.16 (95%CI 2.21-4.53, p<0.001], respectively as shown in Figure 1. CA+CS+ occurred in 7.3%, with the strongest association with higher long-term mortality [adjusted HR 5.36 (95%CI 3.80-7.55), p<0.001]. Using flexible parametric models with B-splines and landmark analysis, the increased mortality was restricted to the first ~10 months after STEMI. In addition, among CS patients, overall mortality rates were higher at all CS timings, pre-, during and post-procedure (all with p<0.001). In contrast, CA during initial cardiac catheterization was not associated with overall mortality (p<0.183), while both CA pre- and post-procedure (all with p<0.001) were associated with higher mortality.

Conclusion:
CS and CA complicating patients presenting with STEMI were associated with higher long-term mortality rate, especially in the first 10 months. While CS at any time frame appeared to impact clinical outcomes, only CA pre- and post- cardiac catheterization were associated with higher mortality rates.
Abstract 4145174: Impact of chronic reductive stress on myocardial proteome turnover: Insights into proteotoxicity and predictive cardiac remodeling
Authors: Namakkal-Soorappan Rajasekaran , WANG DING , NG CHUN , Devarajan Asokan , Challa Anil Kumar , Ping Peipei
Published: November 2024

Background:
Protein half-life and turnover are crucial for cellular function, especially under basal and stress conditions, often contributing to proteinopathies. While the impact of oxidative stress (OxS) on proteostasis is well-documented, the role of reductive stress, an overabundance of antioxidant status, in proteotoxic cardiac disease remains elusive.

Hypothesis:
Tested whether chronic reductive stress (cRS) impairs protein turnover and induce proteotoxic cardiac disease.

Methods:
In transgenic mice expressing constitutively active Nrf2 (caNrf2-TG) and non-transgenic controls (n=6/gp.), we examined the half-life and turnover rates of the myocardial proteome using D2O labeling and mass spectrometry.

Results:
We observed significant changes in the half-life of over 1,700 proteins, with approximately 1,200 proteins exhibiting increased half-life at 3 months, despite no noticeable defects in cardiac structure and function. Under OxS induced by isoproterenol (ISO), about 700 proteins showed reduced half-life, underscoring distinct regulatory mechanisms in protein turnover between cRS and OxS. Proteins with altered half-lives were involved in key cellular functions, including metabolism, signal transduction, immune response, transport, and cell cycle regulation under cRS, revealing novel targets undetected in an OxS context. Notably, distinct positive adaptive compensatory (59; p<0.05) and maladaptive pathologic (58; p<0.05) responses were observed, resulting in unusual protein stabilization and aggregation, leading to proteotoxic stress under cRS. Comparing transcript levels and protein half-life/turnover (HL/TnO) revealed non-linear metrics for subsets of proteins under cRS. Furthermore, bioinformatic predictions identified potential post-translational modification sites in critical proteins with extended half-lives, correlating with the onset of myocardial remodeling in cRS hearts at 3 months, as indicated by altered Tie index and irregular vector velocities of regional wall motions.

Conclusion:
Our findings highlight the importance of prolonged protein half-life and reduced turnover, along with unchanged or decreased transcription, as predictive markers for proteotoxic cardiac disease.
Abstract 4145180: Prognostic value of baseline Residual Inflammatory Risk and Residual Triglyceride Risk in patients undergoing Percutaneous Coronary Intervention with optimally managed LDL Cholesterol
Authors: Di Muro Francesca , Vogel Birgit , Sartori Samantha , Bay Benjamin , OLIVA ANGELO , Gitto Mauro , Smith Kenneth , Krishnan Prakash , Sweeny Joseph , Moreno Pedro , Leone Pier Pasquale , Krishnamoorthy Parasuram , Kini Annapoorna , Dangas George , Sharma Samin , Mehran Roxana
Published: November 2024

Background:
Triglycerides (TG) denote residual triglyceride risk (RTR) while hsCRP indicates residual inflammatory risk (RIR) and both are associated with adverse cardiovascular events.

Question:
In patients undergoing PCI with optimally managed LDL cholesterol (LDL-C), what are the contributions of RTR and RIR to cardiovascular risk?

Aim:
To investigate the associations of RTR and RIR with major adverse cardiac events (MACE) in patients undergoing PCI with optimal LDL-C levels.

Methods:
We evaluated consecutive patients with optimal LDL-C (<70 mg/dL) undergoing PCI at a large tertiary center between 2012 and 2022. Patients were categorized into four subgroups according to baseline TG and hsCRP: (i) No residual risk (hsCRP <2 mg/L + TG <150 mg/dL); (ii) RTR alone (hsCRP <2 mg/L + TG ≥150 mg/dL); (iii) RIR alone (hsCRP >2 mg/L + TG <150 mg/dL); (iv) Combined RIR and RTR (hsCRP ≥2 mg/L+ TG ≥150 mg/dL). Known causes of elevated hsCRP and hsCRP > 10 mg/L were exclusion criteria. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, or stroke. A Cox regression model adjusted for multiple covariates was performed to analyze outcomes using patients without residual risk as a reference.

Results:
A total of 9,446 patients were included in the analysis. Of these, 5,339 showed no residual risk, 3,009 RIR only, 555 RTR only, and 543 exhibited a combination of RIR and RTR. After adjustment, RIR was significantly associated with an increased risk of MACE independently of RTR (p<0.001, adj. HR: 1.80, 95% CI: 1.41-2.29 for no RTR and p=0.002, adj. HR: 1.90, 95% CI: 1.27-2.86 for RTR). This was primarily driven by all-cause mortality. Conversely, in patients with only RTR, MACE and all-cause death rates were numerically higher but risk estimates were not statistically significant after adjustment (
Figure 1
).

Conclusions:
Among patients undergoing PCI with optimally managed LDL-C, RIR was associated with an increased risk of MACE, while RTR did not impact outcomes. HsCRP may be used over TG to stratify the risk for adverse cardiovascular events after PCI.
Abstract 4145196: The role of extracellular vesicle-mediated interorgan crosstalk in obesity and risk of arrhythmias
Authors: Limpitikul Worawan , Xiao Ling , Chatterjee Emeli , Sheng Quanhu , Das Saumya
Published: November 2024

Background:
The worldwide prevalence of obesity has increased in the past decades. Obesity is known to be epidemiologically associated with an increased risk of sudden cardiac death (SCD). However, the mechanisms underlying this phenomenon are not completely understood. We hypothesize that the crosstalk between metabolic organs, such as adipose tissue, and cardiac tissues may contribute to cardiac electrical and structural remodeling that ultimately increases the propensity for SCD; and that extracellular vesicles (EVs), lipid membrane-delimited particles containing diverse cargo (protein, nucleic acids, and metabolites), are as potential key mediators of these interorgan communications.

Method:
Plasma samples were obtained from 5 lean and 6 obese patients without a history of arrhythmias or heart failure (patients were matched by age, sex, and comorbidities). Small EVs (sEVs) were extracted from patients’ plasma and characterized. These sEVs were used to treat human induced pluripotent stem cell-derived ventricular cardiomyocytes (iPSC-vCMs). Action potentials of sEV-treated iPSC-vCMs were measured via optical mapping. Lastly, plasma extracellular small RNAs were extracted and sequenced.

Results:
IPSC-vCMs treated with sEVs derived from obese patients have significantly prolonged action potential duration (APD) at 1-Hz pacing, compared to those treated with EVs from lean counterparts (Figure 1, 589±8 ms vs. 540±11 ms, p < 0.001, n = 2 differentiations) without significant difference in spontaneous contraction rate between the two groups. Preliminary differential gene expression analysis of obese vs. lean plasma extracellular small RNAs demonstrates enrichment in critical signaling pathways, including those involved in calcium homeostasis, reactive oxygen species, fibrosis, and mitochondrial energetics.

Conclusion:
An increased APD in iPSC-vCMs treated with plasma-derived EVs from obese patients correlates with QT interval prolongation, a known risk factor for SCD which is epidemiologically observed in obese populations. Further in-depth analysis to pinpoint targetable EV cargo may shed light on novel mechanisms responsible for obesity-related SCD and potential preventive strategies for SCD in this patient population.
Abstract 4145209: Death on Admission- Characterizing 30-Day Mortality in Patients Admitted to the Coronary Care Unit for Heart Failure Following the COVID-19 Pandemic
Authors: Ghadiali Tejal , Doshi Pratik , Das Anushka , Jinno Stephanie , Fong Michael
Published: November 2024

Background:
Acute decompensated heart failure accounts for an increasing proportion of hospitalizations in the United States and is linked to high readmission and 30-day mortality rates. Prior studies suggest up to 17% mortality rate within 30 days for patients admitted with heart failure.

Research Questions/Hypothesis:
We present an analysis characterizing patients who experienced mortality within 30 days of admission at a large safety net hospital following the COVID-19 pandemic.

Methods/Approach:
A retrospective review was conducted for all heart failure admissions of patients
>
18 years of age admitted to the coronary care unit (CCU) at Los Angeles General Medical Center from January to December 2021 after the peak of the COVID-19 pandemic. Demographics, insurance information, drug use, medication use, heart failure etiology, and CCU interventions were indexed. The primary outcome was all-cause mortality.

Results/Data:
172 patients were identified during the study period. 10% of patients died within 30 days of admission, of which 94% died during the same admission. Of patients who died during index admission, 88% had heart failure with reduced EF. None of these patients were on all four pillars of guideline-directed medical therapy (GDMT), with 33% on one or no GDMT medications.

There was not a statistically significant difference in mortality rate when comparing those with active stimulant use 5/60 (8%) to those without active illicit drug use 12/112 (11%) (RR 0.79, 95% CI, p= 0.64).

9/17 (53%) patients died of refractory cardiogenic shock, 5/17 (29%) were found in cardiopulmonary arrest of unknown etiology while undergoing treatment for acute decompensated heart failure. Two patients (12%) died of septic shock while 1/17 (5%) died of hemorrhagic shock related to chronic liver disease.

Conclusion(s)
The COVID-19 pandemic exacerbated significant healthcare inequalities, especially for urban underserved populations leading to late presentations of disease and worse outcomes, however, based on our data the overall inpatient mortality rate remained largely similar to pre-pandemic values.
Abstract 4145223: Impact of High Lipoprotein(a) Levels on 5-year Clinical Outcomes following Percutaneous Coronary Intervention with Drug-eluting stent in Korean population
Authors: Rha Seung-Woon , Choi Byoung Geol , Ahn Woo Jin , hyun sujin , Cha Jinah , Choi Se Yeon , Sinurat Markz , Park Soohyung , Choi Cheol Ung , Park Chang Gyu , Oh Dong Joo
Published: November 2024

Background:
This study evaluated the association between elevated levels of Lipoprotein(a) [Lp(a)] and the long-term risk of recurrent ischemic events in patients who underwent percutaneous coronary intervention (PCI), and tracked changes in Lp(a) over time.

Methods:
The study population was enrolled from the Korea University Guro hospital (KUGH)-PCI registry from January 2004 to January 2018. A total of 5,790 patients (pts) who underwent PCI with drug-eluting stents(DESs), and have been completed clinical follow-up for 5 years. All subjects were divided into two groups according to Lp(a) level; Lp(a)≥50 mg/dL (n=319pts), Lp(a)<50 mg/d (n=1701pts).

Results:
The Lp(a)≥50 group was 15.8% (319/2020) of the total. Although there were more males (59.5% vs. 68.7%, P=0.001) in the Lp(a)<50 group, baseline, angiographic and procedural characteristics were well balanced between the two groups. In a 5-year clinical follow-up, compared to the Lp(a)<50 group, the Lp(a) ≥50 group had significantly more cardiovascular events, including myocardial infarction (7.5% vs. 3.5% P=0.001), repeated-PCI (20.3% vs. 13.6% P=0.002), and stent thrombosis (4.0% vs. 1.8% P=0.015). The use of statins or ezetimibe did not significantly reduce Lp(a) levels between the time of PCI and up to 1 year in the Lp(a) ≥50 group.

Conclusion:
This observational study demonstrated that elevated baseline Lp(a) levels in patients who underwent PCI were significantly associated with recurrent ischemic events. The prescription of statins or ezetimibe at discharge did not significantly reduce Lp(a) levels up to one-year follow-up.