bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12495: Modes of In-Hospital Death in Patients With Cardiogenic Shock (CS): An Analysis From the Critical Care Cardiology Trials Network (CCCTN)
Authors: Singal Sachit , Bofarrag Fadel , Bohula Erin A , Baird-Zars Vivian , Katz Jason N , Van Diepen Sean , Morrow David , Berg David
Published: December 2023

Introduction:
Mortality from cardiogenic shock (CS), a syndrome of multi-organ system dysfunction, remains high. However, data regarding how patients with CS expire are limited and may have implications for designing clinical trials, identifying therapeutic strategies, and improving outcomes.

Aim:
We sought to describe primary modes of in-hospital death among patients admitted with CS to cardiac intensive care units (CICUs).

Methods:
CCCTN is a multi-national research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Using standardized definitions, site investigators classified the direct mode of in-hospital death for patients with CS. Categories included 8 possible modes of cardiovascular (CV) and non-CV death (
Fig
). Subgroups defined by cardiac arrest prior to CICU admission and use of mechanical circulatory support (MCS) were explored.

Results:
Among 1098 CS cases captured from 10/2021-09/2022, 358 (32.6%) died during the index hospitalization with a median time to death of 4.3 (Q1-Q3, 1.1-10.9) days from CICU admission. Among the deaths, 50%, 41%, and 9% occurred in the context of HF-CS, AMI-CS, and secondary CS, respectively. Overall, mode of death was CV in 82% of cases (
Fig A
). Refractory CS was the dominant mode of death (66%), followed by arrhythmia (13%), anoxic brain injury (6%), and respiratory failure (5%;
Fig A
). Compared to patients without preceding cardiac arrest, those with cardiac arrest prior to CICU admission were more likely to die from anoxic brain injury (10% vs. 1%; p<0.01;
Fig B
). Compared to patients managed without MCS, those with MCS were more likely to die from refractory shock (p<0.01), either cardiogenic (74% vs. 61%) or non-cardiogenic (6% vs. 3%;
Fig C
).

Conclusions:
Most in-hospital deaths in patients with CS are related to direct CV causes, particularly refractory CS. However, there is potentially important heterogeneity in mode of death across subgroups defined by preceding cardiac arrest and use of MCS.
Abstract 12498: AAV-Mediated LINC Complex Uncoupling Ameliorates Pathology in a Mouse Model of
LMNA
Dilated Cardiomyopathy
Authors: Werner Hendrikje , Gan Esther S , Loh Connie , Ng Jennifer , Khaing Nyein Thet , Zhang Jinqiu , Ong Mervyn , Lee John , Russell David W , Tan Yann Chong , Stewart Colin , Burke Brian , Lee Yin Loon
Published: December 2023

Mutations in the
LMNA
gene, encoding lamin A/C, are one of the most frequent genetic causes of dilated cardiomyopathy. While gene therapy using adeno-associated virus (AAV) vectors show promise for the treatment of monogenic diseases,
LMNA
DCM mutations tend to be autosomal dominant and gain-of-function, precluding typical gene replacement approaches.

Lamin A/C forms a filamentous network, the nuclear lamina, underlying the nuclear envelope that is thought to function in maintaining structural integrity of the nucleus by resisting cytoskeletal forces transmitted to the nucleus during cardiac contraction. Our hypothesis is that disruption to the lamin A/C network leads to nuclear envelope rupture as the weakened nuclear lamina cannot resist excess cytoskeletal force. Uncoupling the linkage between the cytoskeleton and nucleus might therefore reduce
LMNA
-associated pathology. This linkage is known to be mediated by the nuclear envelope-localized linker of nucleoskeleton and cytoskeleton (LINC) complex. Using AAV-mediated expression of a LINC complex uncoupling transgene, GSLA01, we were indeed able to prevent the progression of ventricular dilation, cardiac fibrosis, and decline in ejection fraction observed in a
LMNA
dilated cardiomyopathy mouse model.

We decided to explore structure-function relationships in GSLA01 in our lead optimization studies. We generated a series of truncations of full-length GSLA01 comprising different lengths of its coiled coil domain.
In vitro
assays indicated that most truncations examined were able to uncouple the LINC complex. Selected truncations were delivered using AAV to
LMNA
DCM mice after inducing cardiac-specific deletion of
Lmna
with tamoxifen. Full-length GSLA01 extended the lifespan of
LMNA
DCM mice from 39 to ~170 days. The truncations mostly performed on par or better than full-length GSLA01 in extending the lifespan of
LMNA
DCM mice, to more than 250 days for certain constructs.

Reducing cytoskeletal force transmission to the nucleus by uncoupling the LINC complex appears to be a viable strategy for treating
LMNA
-linked pathology, and multiple GSLA01 truncation variants can be used to achieve this effect.
Abstract 12610: Outcomes of Patients With Cancer and Acute Myocardial Infarction-Associated Cardiogenic Shock Managed With Temporary Mechanical Circulatory Support
Authors: Leiva Orly , Yang Eric H , Cheng Richard K , Pauwaa Sunil , Katz Jason N , Alvarez-Cardona Jose , Bernard Samuel , Alviar Carlos L
Published: December 2023

Introduction:
Cardiogenic shock (CS) is a leading cause of in-hospital death among patients with acute myocardial infarction (AMI). Temporary mechanical circulatory support (tMCS) is used in AMI-CS and may improve end-organ perfusion at the risk of bleeding/thrombosis. Patients with cancer are at high risk of AMI and CS and are at risk of bleeding and thrombosis. However, there is limited data on the outcomes of patients with cancer and AMI-CS managed with tMCS.

Methods:
Adult patients with AMI-CS managed with tMCS from January 2006 to December 2018 with and without cancer were identified within the National Inpatient Sample. Propensity score matching (PSM) was performed to match 1 cancer patient to 10 non-cancer controls. Primary outcome was in-hospital death and secondary outcomes were major bleeding and thrombotic complications. Temporal trends of tMCS use in cancer patients were investigated.

Results:
Patient characteristics after PSM are described in Table. After PSM, 1,287 individuals with and 12,870 without cancer were included. Patient characteristics were well-balanced between cancer and non-cancer groups after PSM. After PSM, there was no difference in death (OR 1.00, 95% CI 0.88 - 1.13) or thrombotic complications (OR 1.10, 95% CI 0.91 - 1.34) between patients with and without cancer. Patients with cancer had higher risk of major bleeding (OR 1.29, 95% CI 1.15 - 1.46).

Conclusions:
Among patients hospitalized for AMI-CS managed with tMCS, cancer was associated with increased major bleeding but similar mortality and thrombotic risk. Future investigation is needed in order to further characterize and improve outcomes for this increasingly common patient population.
Abstract 12631: Recognizing and Predicting Drug-Induced Type I Brugada Pattern Using ECG-Based Deep Learning
Authors: Pannone Luigi , Calburean Paul A , Monaco Cinzia , Della Rocca Domenico G , Sorgente Antonio , Almorad Alexandre , Bala Gezim , Ramak Robbert , Overeinder Ingrid , Ströker Erwin , Pappaert Gudrun , La Meir Mark , BRUGADA Pedro , Sieira Juan , Sarkozy Andrea , Chierchia Gian Battista , de Asmundis Carlo
Published: December 2023

Introduction:
Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects and drug-induced BrS accounts for 55-70% of all BrS patients.

Aims:
This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis.

Methods:
Consecutive patients that underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a DCNN was trained to recognize and predict BrS type I pattern. The resultant network is referred to as BrS-Net.

Results:
A total of 1188 patients were included of which 361 patients (30.3%) developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS-Net recognized a BrS type I pattern with an AUC-ROC of 0.945 (0.921 - 0.969). The best predictive performance was obtained when predictions for all ECG leads were combined using a machine learning (ML) technique, Figure 1. When trained and evaluated on ECG tracings at baseline, before ajmaline, BrS-Net predicted the development of a BrS type I pattern during ajmaline with an AUC-ROC of 0.805 (0.736 - 0.845). The best predictive performance was obtained when predictions for all ECG leads were combined using a ML technique, Figure 2.

Conclusions:
BrS-Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS-Net can predict from baseline ECG the eventual development of a BrS type I pattern after ajmaline with good performance in an unselected population.
Abstract 12660: Outcomes of Pregnancy-Associated Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Ansari Umair A , Haseeb Shahan , Masoud Ahmed T. , Chhetri Chandra , Khan Toqeer , Bilal Muhammad Ibraiz , Zulqarnain Muhammad , Shah Tara
Published: December 2023

Background:
Cardiovascular disease is the leading cause of maternal mortality worldwide. The aim of this systematic review and meta-analysis was to investigate complications associated with Pregnancy-associated myocardial infarction (PAMI), which has been linked to various obstetric and fetal complications.

Methods:
We included a total of 11 studies which reported complications in women who had myocardial infarction (MI) during pregnancy. Our outcomes included maternal mortality, postpartum hemorrhage, postpartum infection, preterm labor, eclampsia and pre-eclampsia. Analysis was performed to calculate the pooled proportions. Data was pooled as mean differences or risk ratio and 95% confidence interval (CI) was used.

Results:
Mortality was reported in 7.6% of women who had MI with effect estimate 0.189, 95% CI [0.113, 0.266] (Fig 1a). Incidence of postpartum hemorrhage was reported in 13% of women with effect estimate 0.143, 95% CI [0.060, 0.226] (Fig 1b) and postpartum infection was reported in 15.1% with effect estimate 0.269, 95% CI [0.030, 0.507]. Incidence of eclampsia and pre-eclampsia was reported in 10.98% with effect estimate 0.213, 95% CI [0.125, 0.301] (Fig 2a). Incidence of pre-term labor was reported in 12.87% with effect estimate 0.313, 95% CI [0.116, 0.510] (Fig 2b).

Conclusion:
Our study demonstrated that PAMI was associated with higher rates of major obstetric complications including maternal mortality, postpartum hemorrhage, pre-term labor, pre-eclampsia, eclampsia and postpartum infection.
Abstract 12687: Evaluating a Coronary Artery Disease Polygenic Risk Score Screening Strategy in a Diverse Patient Cohort at UCLA
Authors: Boulier Kristin , Ding Yi , Venkateswaran Vidhya , Pasaniuc Bogdan
Published: December 2023

Introduction:
Recent efforts to predict and mitigate coronary artery disease (CAD) risk have incorporated polygenic risk scores (PGS). Few studies examine the clinical impact of these PGS screening strategies or quantify their performance in clinical terms. Here we estimate the number needed to screen (NNS) of a PGS screening strategy for CAD based using a diverse electronic health record (EHR) linked biobank at UCLA Health.

Methods:
We leveraged longitudinal EHR data to conduct a synthetic trial. We assumed PGS screening was performed on 6/1/2013 for patients established prior to 1/1/2013 or 6 months into follow time if established later. Patients with preexisting cardiovascular disease or strong statin indications (LDL > 190, diabetes or already on statins) are excluded. Patients with PGS scores in the top 5% of their genetic ancestry groupings (European, East Asian, African, Hispanic) are assumed to have been started on statins for the median 6.9 years of follow up. CAD diagnosis during follow up time was determined by ICD codes. NNS to prevent one CV event is calculated from cohort size and events assuming a statin number needed to treat of 50.

Results:
Of 33,789 adults, 17,074 were low risk and eligible for PGS screening (35% male with a mean age of 44). NNS to detect one CAD diagnosis was 351, 359, 814, 159 in the European, Hispanic, East Asian and African ancestry groups and NNS to prevent one cardiovascular event was 17,550, 17,950, 40,700, 7,950 respectively.

Conclusion:
Although PGS accuracy is lower in African ancestry individuals as compared to Europeans, the clinical utility of this PGS-based screening is highest in African ancestries due to increased baseline rates of disease in the African genetic ancestry grouping. Our results demonstrate that PGS accuracy is distinct from clinical utility of PGS-based strategies. Evaluation of screening strategies rather than accuracy alone will be required before PGS screening implementation.
Abstract 12711: Stent Length as a Predictor of Target Vessel Revascularization in Patients Treated With Drug-Eluting Stents
Authors: Mishaev Raffael , Codner Pablo , Perl Leor , Bental Tamir , samara abed , Greenberg Gabriel , Kornowski Ran , vaknin-assa hana
Published: December 2023

Background:
While several factors have been shown to increase the risk of stent thrombosis, most cases of target vessel revascularization (TVR) are due to in-stent restenosis (ISR) and have not been fully evaluated. Objectives: Our aims were to identify predictors of early and late TVR after drug-eluting stents (DES) implantation in a large prospective registry, focusing on stent length.

Methods and Results:
We analyzed rates of TVR according to stent length in a prospective registry of 14,447 all-comers treated with angioplasty and DES implantation in our institution. Patients were divided into quartiles according to stent length - mean 21mm - percentile 25 (Q1) 15mm, 50 (Q2) 18mm, 75 (Q3) 26mm and 100 (Q4) 32mm. At baseline patients had similar rates of diabetes mellitus, congestive heart failure and left ventricular ejection fraction. Patients in the first quartile tend to be older, more commonly of female gender, with higher rates of GFR<60, anemia, and unprotected LM angioplasty. At 4 years follow-up, rates of TVR and MACE were higher in patients with longer stents; 8.5%, 9.8%, 10.4% and 16.1% (p<0.001) and 25.3%, 26.6%, 27% and 28.4% (p=0.031); for TVR and MACE in Q1, Q2, Q3 and Q4 groups of patients; respectively. There were no significant differences in the rates of all-cause death amongst patients in different quartiles. Furthermore, at multivariate Cox-regression analysis length of stent was found to be a significant independent predictor for TVR (OR 1.25 95.0% CI 1.11 - 1.42; p<0.001).

Conclusion:
From the analysis of a large cohort of all-comer angioplasty patients who were treated with DES, stent length emerged as an independent predictor of TVR and MACE.
Abstract 12733: The Effect of Mavacamten Treatment on Hemolysis Biomarkers in Patients With Obstructive Hypertrophic Cardiomyopathy in the EXPLORER-HCM Study
Authors: Wang Zhaoqing , Anderson Warren , Sehnert Amy J , He Aiqing , Kurio Gregory , olivotto iacopo , Schafer Peter
Published: December 2023

Introduction:
In patients with obstructive hypertrophic cardiomyopathy (HCM), blood flow changes from left ventricular outflow tract (LVOT) obstruction can lead to hemolysis and release of red blood cell proteins into circulation. Increased cell-free plasma hemoglobin (Hb) and reduced haptoglobin (Hp) are biomarkers of intravascular hemolysis. Mavacamten, a cardiac myosin inhibitor, reduced LVOT obstruction in the phase 3 EXPLORER-HCM study; however, its effect on hemolysis biomarkers is unknown.

Aim:
To assess the effect of 30 weeks of mavacamten treatment versus placebo on levels of intravascular hemolysis biomarkers in patients with obstructive HCM.

Methods:
Hemolysis biomarkers were measured as part of exploratory proteomic analyses from randomized EXPLORER-HCM (NCT03470545) patients at baseline and Week 30 (mavacamten, n = 115; placebo, n = 120) using a proteomic platform (SomaScan v4.1).

Results:
At Week 30, mavacamten treatment showed decreases in cell-free plasma Hb (Log
2
fold change = -1.57, FDR = 1.7х10
-4
) and increases in cell-free plasma Hp (Log
2
fold change = 1.83, FDR = 1.2х10
-4
) vs placebo (Figure). Hb and Hp levels were negatively correlated at baseline and at Week 30. In general, patients can be grouped into high- or low- hemolysis biomarker profile (high Hb with low Hp or low Hb with high Hp, respectively) at baseline and Week 30. Patients who received mavacamten and changed from high- to low hemolysis biomarker profile at Week 30 trended towards greater LVOT reductions under resting and Valsalva conditions. No changes were detected for either group in whole blood Hb or hematocrit.

Conclusions:
Reduced cell-free plasma Hb and increased cell-free plasma Hp levels, suggest a reduction in intravascular hemolysis by mavacamten in obstructive HCM. These results are consistent with improved hemodynamic effects (less outflow obstruction) and indicate that mavacamten may reduce shear forces on red blood cells in the heart.
Abstract 12738: Comparing Costs of Non-Invasive Cardiac Diagnostic Tests and Deferred Testing for Incident Chest Pain - A Population-Based Study
Authors: Roifman Idan , Chu Anna , Austin Peter , Douglas Pamela S , Wijeysundera Harindra C
Published: December 2023

Introduction:
Cardiac non-invasive diagnostic tests (NIT) for patients with suspected coronary artery disease cost > $3 billion annually in the US, and may be overused. Consequently, comparing costs of different NIT strategies, including deferred testing, is of urgent importance to healthcare planning.

Methods:
We compared population-based downstream costs between patients undergoing evaluation for chest pain in Ontario, CA with one of four NIT tests (exercise stress testing (GXT), stress echocardiography, cardiac computed tomography angiography (CCTA) and myocardial perfusion imaging (MPI)) as well as no-testing. To compare costs among the tested and non-tested groups, we used a log-gamma generalized linear model to account for the skewed distribution of health care costs, adjusting for relevant clinical covariates.

Results:
Of 2,340,699 included patients, 481,170 (21%) received one of four NITs: GXT: 254,492 (53%), MPI: 154,137 (32%), stress echo: 69,160 (14%), and CCTA: 3,381 (<1%). After adjustment for patient characteristics including cardiac risk factors, frailty and location (Table 1), receipt of any NIT was associated with a 12% reduction in downstream 1-year mean costs compared to those without an NIT (cost ratio 0.88, 95%CI 0.87, 0.89). Comparing the different testing strategies with no testing, both GXT (cost ratio 0.80, 95%CI 0.79-0.81) and stress echocardiography (cost ratio 0.82, 95%CI 0.81-0.83) had lower downstream costs, while both MPI (cost ratio 1.26, 95% CI 1.25, 1.27) and CCTA (cost ratio 1.29, 95% CI 1.23, 1.35) had higher downstream costs.

Conclusions:
In a large (>2 million) population-based cohort with incident chest pain, receipt of any type of non-invasive testing was associated with a 12% reduction in downstream costs compared to no testing. GXT and stress echocardiography had the least downstream costs, whereas CCTA and MPI had the highest costs. These findings may help inform testing decisions in chest pain patients.
Abstract 12750: Three Dimensional Environment for Efficient and Large Scale Generation of Smooth Muscle Cells From HiPSCs
Authors: Green Akazha , Wei Yuhua , Ye Lei , Zhang Jianyi J
Published: December 2023

Introduction:
Smooth muscle cells (SMCs) play an important role in maintaining vascular homeostasis and the development of diseases. We assess feasibility and efficacy of differentiation human induced pluripotent stem cells (hiPSCs) to SMCs in a 3-dimension (3D).

Methods:
hiPSCs were cultured in shaker flasks or PBS-0.1 Vessels for 48 h. Differentiation initiated (as day 0) by culturing hiPSC spheroids in RPMI+B27 without insulin (B27-) and CHIR99021 (CHIR) for 24 h. Day 1, medium was replaced with RPMI+B27-, platelet derived growth factor β (PDGF-β), and transforming growth factor β1 (TGFβ1) for 48 h, refreshed medium on day 3 for 48 h. Day 5, differentiating hiPSC-spheroids were dissociated to single cells and cultured as monolayer in RPMI +4% FBS, PDGF-β, and TGFβ1 for 72 h. Refreshed medium day 8 for 72 h. Differentiation efficiency was determined by flow cytometry and fluorescence immunostaining. The biological function of 3D differentiated SMCs was assessed
in vitro
and in a mouse model of ischemic limb disease
in vivo
.

Results:
Both 3D differentiation methods efficiently differentiated hiPSCs into SMCs. Flow cytometry showed that 99.4% cells expressed smooth muscle actin (SMA), 97.9% expressed myosin heavy chain 11 (MYH11), 95.1% expressed SM22, 97.5% expressed calponin, and 97.7% expressed calveolin-3 using shaker flasks. They were 99.6% for SMA, 97.9% for MYH11, 97% for SM22, 89.6% for calponin, and 87.2% for calveolin-3, respectively, using PBS-0.1 Vessels. Mean SMC cell number obtained was 4.56 x 10
7
for shaker flasks and 5.69 x 10
7
for PBS-0.1 Vessels, respectively, which were significantly higher than hiPSCs differentiated in monolayer (5.7x10
6
). Fluorescence immunostaining confirmed that SMCs differentiated from both methods expressed SMA, MYH11, SM22, Calponin, and calveolin-3. Differentiated SMCs migrated in scratch assay, contracted in response to U-46619, an analog of the endoperoxide prostaglandin, and formed tubular structure on Matrigel
in vitro.
Fluorescence angiogram imaging showed that SMC transplantation effectively induced perfusion in mouse ischemic limbs.

Conclusions:
Both 3D differentiation methods, using shaker flasks or PBS-0.1 vessels, efficiently differentiated hiPSCs into large scales of functional SMCs.
Abstract 12757: Osimertinib-Associated Cardiotoxicity: Insights Into Echocardiographic Changes and Patients at Increased Risk
Authors: Le Jonathan N , Gasho Jordan O , Peony Olivia , Singh Asneh , Silos Katrina , Kim Sungjin , Nguyen Anthony , Reckamp Karen L , Sankar Kamya , Nikolova Andriana P , Atkins Katelyn M
Published: December 2023

Introduction:
Osimertinib is a third-generation epidermal growth factor (EGFR) tyrosine kinase inhibitor used in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). While osimertinib has known cardiotoxicity risks, there is a paucity of detailed transthoracic echocardiographic (TTE) changes and known predictors.

Hypothesis:
Osimertinib is associated with TTE changes other than reduced EF in patients with NSCLC; further, those with pre-existing cardiac risk factors may be at increased risk of cardiotoxicity.

Methods:
Single-center retrospective analysis of patients with NSCLC with available TTEs after starting osimertinib between 2007-2022. Cardiac event (any grade ≥2 cardiac common terminology criteria for adverse events [CTCAE]) cumulative incidence was estimated and Fine and Gray regressions performed (adjusting for non-cardiac death as a competing risk).

Results:
In total, 85 patients were included (mean age was 68 years, 67% female). Median interval between osimertinib initiation and first follow-up TTE was 17.6 months. After a median follow-up of 35 months, 17 patients developed grade ≥2 CTCAE (2-year cumulative incidence, 19.2%; 95% confidence interval [CI]: 11%-29%). These CTCAEs include QTc prolongation (n = 10), EF decline of ≤50% or ≥10% drop from baseline (n = 5), new valvular regurgitation/stenosis on imaging (n = 5), and supraventricular arrhythmia (n = 3). A pre-treatment TTE was available for 38 patients prior to osimertinib initiation. Comparing post- vs pre-osimertinib TTEs, there was significant LVEF decline (58 ± 11% vs 61 ± 8%), increased diastolic dysfunction (40% vs 32%, mitral regurgitation (49% vs 24%), and tricuspid regurgitation (45% vs 24%), all p <0.01. On multivariable analysis, preexisting arrhythmias (hazard ratio [HR] 3.90; 95% CI 1.11-1.13; p = 0.034) and BMI (HR 1.07, 95% CI 1.00-1.14; p = 0.04) were associated with an increased risk of cardiac events.

Conclusions:
Osimertinib was associated with a nearly 20% 2-year cumulative incidence of cardiac events and multiple echocardiographic changes. BMI is a potential modifiable risk factor to mitigate Osimertinib-associated cardiac events. These findings highlight the need for close surveillance in these higher cardiac-risk patients with NSCLC.
Abstract 12761: Pathogenic Genetic Variants in Patients With Heart Transplant Due to Ischemic and Non-Ischemic Cardiomyopathy
Authors: Shabani Mahsima , Heimlich Brett B , Poisner Hannah , Su Yan Ru , Bick Alexander G
Published: December 2023

Introduction:
Current clinical guidelines recommend offering genetic testing to all patients diagnosed with non-ischemic cardiomyopathy (NICM), particularly in patients with a strong family history. The utility of genetic testing more broadly in patients with end-stage heart failure requiring heart transplant (HT) is unknown.

Hypothesis:
Among patients with HT, prevalence of cardiovascular disease (CVD)-associated pathogenic/likely pathogenic (P/LP) variants is higher in those with NICM than those with ischemic cardiomyopathy (ICM).

Methods:
We performed targeted DNA sequencing of 120 mendelian CVD genes in 124 consented patients with a HT, enrolled in the Vanderbilt Cardiac Catheterization Lab Cohort between 2003 and 2021. DNA sequence variation was annotated as P/LP based on ACMG criteria.

Results:
Out of 124 participants with HT, 70 had NICM and 51 had ICM. 22.8% of the NICM group harbored a P/LP variant in
TTN
(n=5),
LMNA
(5),
MYH7
(1),
RYR2
(1),
RBM20
(1),
COL1A2
(1),
PKP2
(1), and
CASQ2
(1). 19.6% of ICM participants harbored a P/LP variant in
LDLR
(2),
RYR2
(1),
TTN
(1),
SDHA
(1),
MYH7
(1),
SGCD
(1),
MYL3
(1),
CASQ2
(1), and
COL1A2
(1). In NICM and ICM patients with a P/LP variant, 94% and 100% had a family history of CVD, respectively. By comparison in those without a P/LP variant, 59% and 73% had a family history of CVD. Out of 124 patients, only 13 had genetic testing through their clinical care, all of which occurred post-transplantation. 5/13 of these patients had a P/LP variant.

Conclusions:
This retrospective study showed a significant yield of genetic testing in HT patients. Notably, the overall prevalence of P/LP variants was nearly identical between NICM and ICM patients, with a higher rate of CM-related variants in the NICM group. We suggest that a genotype-first approach of screening all HT patients for genetic mutations enables earlier identification of actionable variants in HT probands and their family members than the current phenotype-guided approach.
Abstract 12768: Recurrent Hyperkalemia is Associated With Higher Rates of Cardiovascular Outcomes and All-Cause Mortality in Patients With Chronic Kidney Disease: The Revolutionize III Study
Authors: Bakris George L , Agiro Abiy , Greatsinger Alexandra , Sundar Manasvi , Mu Fan , Cook Erin , Guo Helen , Louden Elaine , Colman Ellen , Desai Pooja
Published: December 2023

Introduction:
The impact of recurrent hyperkalemia (rHK) on the time to cardiovascular (CV) outcomes and mortality in patients with chronic kidney disease (CKD) has not been well studied. This real-world study described and compared rates of CV outcomes and all-cause mortality between patients with rHK and matched patients without HK (nonHK).

Methods:
Patients with rHK were matched 1:1 to nonHK controls via exact and propensity score matching with the date of rHK or nonHK as index. Patients were adults with stage 3 or 4 CKD identified from Optum’s de-identified Market Clarity Data spanning 1/2016 to 8/2022. For each outcome sample, the corresponding CV events in baseline were excluded. CV outcomes included major adverse cardiovascular events plus (MACE+; all-cause mortality or inpatient [IP] heart failure, myocardial infarction, or stroke) and IP cardiac arrhythmia. Rates of CV outcomes and mortality were compared between matched cohorts using cause-specific Cox proportional hazard models and reported as hazard ratios (HR) with 95% confidence intervals (CI). Subgroups analyses were conducted by renin-angiotensin-aldosterone system inhibitor (RAASi) use at index.

Results:
Of 6,337 matched pairs, mean age was 73.3 years and 47.7% of patients were female. Patients with rHK compared to nonHK had higher rates of CV outcomes, including MACE+ (N = 5,258, HR=1.53 95% CI=[1.43, 1.65]) and IP arrhythmia (N = 5,485, 1.94 [1.74, 2.16]) (all p<0.001,
Figure 1
). Results were consistent in the RAASi subgroup (MACE+: 1.46 [1.31, 1.63]; IP arrhythmia: 1.84 [1.57, 2.16], both p<0.001). Patients with rHK also had higher rates of mortality (Overall: N = 6,337; 1.29 [1.20, 1.38]; RAASi subgroup: 1.25 [1.11, 1.41], both p<0.001) compared to nonHK controls.

Conclusions:
This study demonstrates that patients with CKD and rHK had significantly higher rates of mortality, MACE+, and IP cardiac arrhythmia compared to matched patients with CKD and nonHK.
Abstract 12823: As Anticoagulation Use Increases, Embolic Events Downtrend in Atrial Fibrillation Hospitalizations
Authors: Vasquez Moises A , Yan Crystal L , Mijares Ivan A , Quintero Martinez Juan , Luna Alvarez Amezquita Jose , mustafa mohammed , Iskander Mina , Lambrakos Litsa , Velasquez Alex , Goldberger Jeffrey J , Mitrani Raul D
Published: December 2023

Background:
Direct oral anticoagulants and Left atrial appendage closure (LAAC) were approved for use in 2010 and 2015, respectively. Data on temporal changes in stroke prevention strategies and rates of embolic complications in atrial fibrillation (AF) in the 2010s decade are limited.

Aims:
Describe trends in long-term anticoagulation (AC), LAAC use, and in-hospital AF associated ischemic stroke (IS), transient ischemic attacks (TIA), and systemic embolic events (SEE) between 2010 and 2019.

Methods:
The national inpatient database was used to identify patients with AF from 2010 to 2019. Data were divided into 2 eras: 2010-2014 and 2015-2019.

Results:
A total of 40,787,136 inpatients with AF were identified: prevalence increased from 18,594,372 in 2010 to 2014 (46%; mean [SD] age 75.5 [12.0] years; 50.3% male) to 22,192,764 in 2015 to 2019 (54%; mean [SD] age 75.1 [11.8] years; 52.5% male). There was a marked increase in long-term AC use (27.2% to 40.2%; P=0.001) and rates of percutaneous LAAC procedures (0.01% to 0.6%; P <0.001) from 2015 to 2019. IS rates among patients with AF increased from 2010 to 2014 (3.5% to 3.8%; P=0.04), with no significant temporal change from 2015 to 2019 (P=0.84). TIA rates declined from 2010 to 2014 (1.2% to 1.0%; P=0.017) and continued a downtrend from 2015 to 2019 (0.9% to 0.7%; P=0.002). There was no temporal change in SEE or the composite outcome of all embolic events from 2010 to 2014, followed by a decline from 2015 to 2019 in SEE (0.5% to 0.4%; P 0.012) and all embolic events (5.1% to 4.8%; P 0.026) (
Figure 1
). Mean rates of major bleeding events increased from 5.7% in 2010-2014 to 9.1% in 2015-2019 (P <0.001).

Conclusion:
In an inpatient AF population, the composite outcome of all embolic events and specifically SEE downtrend from 2015 to 2019, likely due to increased AC use. Further data assessing the risk-benefit ratio of available therapies for stroke prevention in inpatients with AF - AC and LAAC - are needed to optimize personalized strategies.
Abstract 12831: Serum Potassium Levels and Mortality in Heart Failure Patients. A Meta-Analysis
Authors: Chia Jia Ee , Ang Song Peng , Jaiswal Vikash
Published: December 2023

Introduction:
Serum potassium disturbances are frequently observed in patients with heart failure (HF) and can be attributed, to some extent, to comorbidities and the use of diuretics, mineralocorticoid receptor antagonists, and renin-angiotensin-aldosterone system antagonists. Previous studies on the prognostic implications of potassium homeostasis impairment have yielded heterogeneous findings. This meta-analysis aims to evaluate the association between serum potassium levels and mortality in HF patients.

Methods:
A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and the Cochrane Library, to identify relevant studies. The primary outcomes assessed were all-cause mortality and cardiovascular mortality. The DerSimonian-Laird random-effects model was used to pool the outcomes, and the results were presented as hazard ratios (OR) with 95% confidence intervals (CI). Meta-regression was performed to identify potential sources of heterogeneity.

Results:
A total of twelve studies involving 45,678 HF patients were included in the analysis. Among them, 3,298 patients were hypokalemic, 38,328 were normokalemic, and 4,052 were hyperkalemic. The follow-up period was 1.5 (1- 2.8) years. The meta-analysis of adjusted effect sizes revealed that both hypokalemia (HR 1.68, 95% CI: 1.38-2.05, p < 0.001) and hyperkalemia (HR 1.36, 95% CI: 1.17-1.57, p < 0.001) were significantly associated with increased all-cause mortality. When compared to normokalemic patients, those with hypokalemia had a significantly higher risk of cardiovascular mortality (HR 1.77, 95% CI: 1.02-3.07, p = 0.01), whereas no significant association was found for hyperkalemia (HR 1.13, 95% CI: 0.98-1.31, p = 0.10). Univariate meta-regression analysis did not identify any significant moderators of effect size.

Conclusions:
This study reveals a U-shaped relationship between serum potassium levels and all-cause mortality in patients with heart failure. Hypokalemia is additionally associated with cardiovascular mortality.
Abstract 12930: Atrial Myopathy and the Risk of Incident Atrial Fibrillation in People With Newly Diagnosed Cavotricuspid Isthmus-Dependent Atrial Flutter
Authors: Walters Benjamin P , Farbaniec Michael , Gonzalez Mario , Naccerelli Gerald , Maheshwari Ankit
Published: December 2023

Background
New cavotricuspid isthmus-dependent atrial flutter (AFL) is associated with increased risk of incident atrial fibrillation (AF). It is unclear which patients with AFL will develop AF.

Hypothesis:
Patients with new AFL who have co-existing atrial myopathy, detected by measuring left atrial emptying fraction (LAEF) and left atrial reservoir strain (LARS), may be at increased risk for developing AF.

Methods:
There were 210 patients who received an ablation or cardioversion for AFL at a tertiary care medical center between 2015-2022. Patients were excluded for prior AF (118), congenital heart disease (16), valve surgery and heart transplant (9), no echocardiogram available (9), and less than 6 months of follow up (9). Data was obtained by retrospective chart review. Covariates included coronary heart disease, heart failure, diabetes, age, sex, vascular disease, and stroke. Exposure variables included LAEF and LARS. We used Cox proportional hazards models to estimate the risk of AF for LAEF and LARS.

Results:
49 patients (mean age 62.3 years, 18.3% female) met criteria for inclusion, and 18 developed atrial fibrillation over a mean follow up period of 29.9 months (19.7 months). Those who developed AF had lower LAEF and LARS compared to those who did not. For every 5% decrease in LAEF and LARS, there was a 1.79 (1.33, 2.38) and 5.26 (1.75, 16.67)-fold increase in risk of AF after adjustment for covariates.

Conclusion:
Co-existing atrial myopathy, measured by decreased LAEF and LARS, is associated with increased risk of AF in people with new AFL.
Abstract 12947: Restoration of Sinus Rhythm Significantly Improves Left Ventricular Function in Patients With Very Low Ejection Fraction
Authors: Mohanty Sanghamitra , Torlapati PremGeeta , La Fazia Vincenzo Mirco , gianni carola , MacDonald Bryan , Mayedo Angel , Della Rocca Domenico G , Bassiouny Mohamad , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di Biase Luigi , Natale Andrea
Published: December 2023

Introduction:
Left ventricular (LV) dysfunction is a common sequelae of supraventricular tachycardia, especially atrial fibrillation (AF). We evaluated the impact of restoration of sinus rhythm following successful catheter ablation on LV function in AF patients with ejection fraction of ≤20%.

Methods:
Consecutive AF patients with LVEF ≤20% undergoing their first catheter ablation were included in the study. All received isolation of pulmonary veins, left atrial posterior wall and superior vena cava. Additionally, non-PV triggers were ablated at the operator’s discretion. Echocardiogram was performed at baseline and 6 months post-ablation to measure the LVEF. Arrhythmia-monitoring was performed at 1, 3 and 6 months with event recorders, 12-lead ECG and 7-day Holter monitoring.

Results:
A total of 63 patients undergoing catheter ablation for AF were included (age: 62.5 ± 9.9 years, male: 82.5%). Majority of the patients had LVEF of ≤15% (n=48, 76%); remaining 15 patients had LVEF of 16-20%. Mean LA diameter was 4.94 ± 0.57 cm and 82.5% of patients had non-paroxysmal type of AF. Median duration of AF was 27 months. Follow-up echocardiogram at 6 months of follow-up detected significant improvement in LVEF [Mean difference: 15.2 ± 11.7% (p < 0.001)]. All patients were arrhythmia-free at that time point: 47 (74.6%) off-drugs and 16 (25.4%) patients on previously ineffective anti-arrhythmic drugs.

Conclusion:
Restoration of sinus rhythm following successful catheter ablation was associated with significant improvement in LVEF in patients with severe LV dysfunction
Abstract 12974: Sex Differences in Invasive Coronary Angiography at a Large Urban US Hospital
Authors: Chiu Sarah , Yao Shuanglang , Kadariya Dinesh
Published: December 2023

Introduction:
Invasive coronary angiography (ICA) is a common procedure to evaluate for ischemic heart disease. Significant sex differences in referral for invasive coronary angiography as well as intervention have been reported. The aim of the current study was to evaluate the impact of male and female sex on patterns of ICA at a large urban hospital.

Methods:
We retrospectively reviewed hospital procedures performed at UF Health Jacksonville between 2014 and 2018. The electronic health record was queried. Total number of cases and number of cases who did not undergo percutaneous coronary intervention (PCI) or coronary artery bypass graft at the same encounter were retrieved. Chi-square was used to compare groups and odds ratio with 95% confidence interval calculated, and a p-value <0.05 was considered statistically significant.

Results:
A total of 5556 patients underwent ICA with a men (n=3307) to women (n=2249) ratio of 1.47. Similarly, the ratios of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) were lower in women as compared to men. The mean age for male patients was 61±12 years and <3% were <40 years old. The mean age for female patients was 62±13 years and <3% were <40 years old. Female gender was significantly associated with lower likelihood of having intervention with a male versus female odds ratio (OR) of 1.5 [95% CI 1.4-1.7, p <0.001]. However, those females who underwent PCI had the same ratio of receiving balloon angioplasty, stents or atherectomy as compared to males.

Conclusion:
In a large urban US clinical center with a diverse and underserved population, being a woman significantly decreases the likelihood of referral for ICA as well as PCI. Our study aligns with prior investigations and underscores the need for further studies to clarify the underlying causes of these differences.
Abstract 13015: Sex Disparities in Outcomes of Adults With Cardiogenic Shock Using Impella; a Propensity-Matched Analysis
Authors: Ramphul Kamleshun , Memon Rahat A , Dhaliwal Jasninder S , Sombans Shaheen , Ravalani Abhimanyu , Lohana Petras
Published: December 2023

Introduction:
Impella use is one of the mechanical circulatory support options in patients with cardiogenic shock (CS). While recent studies have associated a 47.3% short-term mortality in Impella support for CS, there is a lack of data on sex disparities in its use. We, therefore, conducted a retrospective analysis to analyze its impact.

Hypothesis:
We assessed the hypothesis that females and males have different outcomes following the use of Impella for CS.

Methods:
We explored the 2016-2020 National Inpatient sample for adults with CS and Impella use. Propensity matching was conducted for multiple patient and hospital characteristics. The differences in males and females for various complications were analyzed.

Results:
Our study initially found 57630 cases that matched our selection, with 41455(71.9%) males and 16175(28.1%) females. After propensity matching, Females showed a higher mean age (64.31 vs. 62.82 years, p<0.01), with a higher mean Charlson Comorbidity Index (CCI) score (4.50 vs. 4.25, p<0.01), but a shorter hospitalization ( 15.31 vs. 16.64 days). In addition, females showed higher odds of central line-associated bloodstream infection (CLABSI) (aOR 2.576, 95% CI 1.147-5.788, p=0.022), pulmonary embolism (PE) (aOR 1.544, 95% CI 1.077-2.213, p=0.018), respiratory failure/arrest (aOR 1.124, 95% CI 1.001-1.262, p=0.048) than males, while having lower odds of acute kidney injury (AKI) (aOR 0.727, 95% CI 0.648-0.815, p<0.01). No differences in stroke, sepsis, or death events were found between them.

Conclusions:
In conclusion, there are differences in outcomes between males and females following use of Impella for CS, as females expressed higher odds of CLABSI, PE, respiratory failure/arrest, and lower odds of AKI than males. Future randomized studies in clinical settings and addressing for limitations of our study (such as drug use and duration of various comorbidities) are warranted to improve outcomes between the two cohorts.
Abstract 13017: National Characteristics and Outcomes of Adults With Pulmonary Embolism Undergoing Catheter Directed Thrombolysis Compared to Systemic Tissue Plasminogen Activator
Authors: Dhaliwal Jasninder , Memon Rahat A , Aggarwal Shruti , Ramphul Kamleshun , Sombans Shaheen , Sakthivel Hemamalini
Published: December 2023

Introduction:
Catheter Directed Thrombolysis (CDT) and systemic tissue plasminogen activator (tPA) are commonly used interventions for pulmonary embolism (PE). We aim to compare these two procedures.

Methods:
Cases of pulmonary embolism in adults were used for our study from the National Inpatient Sample (2016-2020). We compared the characteristics and outcomes of patients undergoing CDT vs. systemic tPA <24 hours after hospitalization.

Results:
We found 16675 cases of PE, with 9130 (54.8%) patients undergoing tPA and 7545 (45.2%) needing CDT. Compared to tPA cases, a lower rate of weekend admission was seen in patients undergoing CDT. Both groups consisted of Whites and were covered primarily by Medicare. Most admissions took place in urban teaching centers, with large bed sizes and in the southern regions of the US. Furthermore, CDT patients were older (mean age 56.2 vs. 52.1 years), involving more patients with hypertension and obesity. However, CDT cases had fewer patients with diabetes, peripheral vascular disease, chronic kidney disease, prior stroke, and drug abuse and reported a lower mean Charlson Comorbidity Index(CCI) score(table 1). tPA patients also had higher rates of atrial fibrillation, ventricular fibrillation, and atrial flutter. Overall, 5.9% of patients undergoing tPA died, while 1.8% died in the CDT cohort (aOR death in tPA 2.604 vs. CDT, 95% CI 2.033-3.335, p<0.01). A higher mortality rate within the first week of hospitalization was also seen in the tPA group (figure 1). tPA cohort also reported higher odds of acute kidney injury(AKI) (aOR 1.484, 95% CI 1.364-1.615, p<0.01) and cardiogenic shock (aOR 3.588, 95% CI 2.990-4.304, p<0.01). Finally, tPa patients had a lengthier stay.

Conclusions:
CDT cases showed lower mortality during the first week of the procedure. Differences in comorbidities exist between the two groups. Further research exploring additional factors may help address current protocols to improve long-term outcomes.
Abstract 13028: Estimating Cardiovascular Event Rates in US Veterans Using the SMART Risk Score
Authors: Ravishankar Milan , Strickland Patrick , Minniefield Nicole , DiGregorio Helene , Weideman Rick , Jacob David , Fernandez Vazquez David , Little Bert , Banerjee Subhash
Published: December 2023

Background:
There is limited data on racial differences in long term cardiovascular (CV) outcomes amongst U.S. veterans.

Methods:
Utilizing the VA Informatics and Computing Infrastructure and the Corporate Data Warehouse we compared 10-year predicted major adverse CV events [MACE, a composite of all-cause death and non-fatal myocardial infarction] in patients referred for cardiovascular consultation between 2003 and 2009 using the SMART risk score with observed rates across racial groups. The SMART risk score classified patients into low 0-9.9%, intermediate 10-19.9%, high 20-29.9%, and very high >=30% risk groups.

Results:
473,136 patients including white (74.7%), African American (15.5%), and other (9.8%) made the study cohort. Observed event rates were significantly higher in African Americans compared with Whites across all SMART risk groups [p<0.001], and highest in the other races, inclusive of Hispanics. These results are depicted in
Figure 1
.

Conclusion:
There is a significantly higher observed 10-year MACE rate in African American veterans compared with their white counterparts across all predicted SMART risk score groups.
Abstract 13052: Clonal Hematopoiesis of Indeterminate Potential Predicts Incident Cardiac Arrhythmias
Authors: Schuermans Art , Vlasschaert Caitlyn , Nauffal Victor , Uddin Md Mesbah , Nakao Tetsushi , Niroula Abhishek , Klarqvist Marcus D , Weeks Lachelle D , Lin Amy E , Saadatagah Seyedmohammad , Lannery Kim , Wong Megan , Hornsby Whitney , Lubitz Steven A , Ballantyne Christie M , Jaiswal Siddhartha , Bick Alexander G , Ellinor Patrick T , Natarajan Pradeep , Honigberg Michael C
Published: December 2023

Background:
Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. Whether CHIP independently predicts new-onset arrhythmias is unknown.

Methods:
UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP (variant allele fraction [VAF] ≥2%), large CHIP (VAF ≥10%) and gene-specific CHIP subtypes with incident arrhythmias were tested using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis (T1 times on cardiac magnetic resonance [CMR]) were also tested.

Results:
This study included 410,879 participants (CHIP:
n
=13,901 [3.4%]; large CHIP:
n
=9,197 [2.2%]). Any and large CHIP were associated with adjusted HRs of 1.11 (95%CI, 1.04-1.18;
P
<0.001) and 1.14 (95%CI, 1.05-1.22;
P
<0.001) for supraventricular arrhythmias, 1.09 (95%CI, 1.01-1.19;
P
=0.029) and 1.13 (95%CI, 1.03-1.25;
P
=0.011) for bradyarrhythmias, and 1.15 (95%CI, 1.00-1.33;
P
=0.054) and 1.22 (95%CI, 1.03-1.45;
P
=0.023) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed increased risk of arrhythmias across mutations in driver genes other than
DNMT3A
(
Figure
)
.
Large CHIP was associated with 1.30-fold odds (95%CI, 1.07-1.59;
P
=0.009) of being in the top quintile of myocardial fibrosis by CMR.

Conclusions:
CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation toward arrhythmia prevention and treatment.

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