bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12103: Intraindividual Variability in Serial Lipoprotein(a) Concentration Among Placebo-Treated Patients in the OCEAN(a)-DOSE Trial
Authors: Gaba Prakriti , O'Donoghue Michelle , Lopez J. A , Rosenson Robert S , Watts Gerald F , Kuder Julia , Im KyungAh , Kassahun Helina , Wang Huei , Wu You , Wang Jingying , Ohman Erik Magnus , Sabatine Marc S
Published: December 2023

Background:
It has been suggested that lipoprotein(a) [Lp(a)] concentrations are stable over time and need to be measured only once in a lifetime. However, data assessing intraindividual variability in Lp(a) concentration are limited.

Methods:
OCEAN(a)-DOSE, a phase 2, randomized trial of the Lp(a)-lowering siRNA therapy olpasiran, enrolled 281 patients with atherosclerotic cardiovascular disease (ASCVD) and Lp(a) >150 nmol/L. Analyses were conducted in patients randomized to placebo (n=53) with serial Lp(a) values every 4 to 12 weeks through 72 weeks (820 total serum samples). Intra-individual biological variation (CV
i
) was calculated as standard deviation of Lp(a) values over time in an individual divided by the mean of those values. All Lp(a) values were measured using the Roche Tina-quant Gen.2 assay reporting in molarity (assay CV 0.7% at 105 nmol/L).

Results:
Median baseline Lp(a) in the placebo arm was 246 nmol/L (IQR 200-343); median number of Lp(a) measurements per subject was 16. Whereas the overall Lp(a) concentration remained similar across visits (standard deviation 2.6% of the mean), the intra-individual variation over time (CV
i
) was 10% [SD 3.9%] of the mean. This variation remained similar across a range of mean Lp(a) values for each participant (Figure). The absolute observed differences in the placebo arm over time across all visits was 22 ± 21 nmol/L (mean ± SD), with a maximum absolute difference of up to 135 nmol/L from an individual patient’s mean. When evaluating outliers, 23% of patients experienced an upward or downward > or equal to 25% change from their individual mean on at least 1 visit, and 51% experienced an upward or downward > or equal to 50 nmol/L change on at least 1 visit.

Conclusion:
Among patients with ASCVD and elevated baseline Lp(a) concentration, there was notable intra-individual variability in Lp(a) concentration over 72 weeks of follow-up. These findings suggest that Lp(a) may need to be measured more than once in a lifetime.
Abstract 12125: Distribution of Myocardial Fibrosis in Patients With Non-Ischemic Cardiomyopathy and Ventricular Tachycardia Based on Genetic Variant
Authors: Weinand Nicholas , Hasegawa Kanae , Hu Tiffany , Richardson Travis
Published: December 2023

Introduction:
Patients with non-ischemic cardiomyopathy (NICM) have an increased propensity to develop arrythmias such as ventricular tachycardia (VT). A significant subset of patients with NICM have an underlying inherited genetic component.

Hypothesis:
This study evaluated the location of substrate for ventricular tachycardia in patients with NICM with proven genetic variants. We sought to characterize patterns of substrate location based on specific genetic variants.

Methods:
Patients referred for VT ablation between October 2018 and November 2022 at a single medical center were evaluated for pathologic genetic variants of known cardiomyopathy-related genes. Electro-anatomic mapping was reviewed for substrate localization.

Results:
Thirty-two patients with pathologic variants were evaluated (age 55 +/- 16 years, 94% male, left ventricular ejection fraction 34 +/- 13%). Mutations in TTN (n=11 of 32), LMNA (n=6 of 32), PKP2 (n=5 of 32), MYBPC3 (n=3 of 32), DSP (n=2 of 32), TTR (n=1 of 32), FNLC (n=1 of 32), AGL (n=1 of 32), DES (n=1 of 32), DSG2 (n=1 of 32), were observed. Mutations in TTN were associated with substrate in the basal periaortic region (100%) and basal septum (50%) (Figure 1). LMNA mutations were associated with mid inferolateral (60%) and apical inferolateral (60%) substrate. Substrate location for individuals with mutations associated with PKP2 were solely observed in the right ventricle.

Conclusion:
Certain genetic variants are associated with reproducible patterns of fibrosis in NICM. Understanding expected patterns of fibrosis based on genetic variants in NICM may facilitate ablation planning.
Abstract 12127: Diagnostic Performance of Fractional Flow Reserve, Instantaneous Wave-Free Ratio and Quantitative Flow Ratio, on the Same Patient and Procedure
Authors: Rodriguez Salinas Cesar Alejandro , Mendez Rodriguez Allan , PONCE DE LEON ENRIQUE , Puron Gonzalez Emma , Azpiri Jose R
Published: December 2023

Introduction:
Contemporary percutaneous coronary intervention (PCI) seeks precision and physiological assessment of coronary artery stenosis. Fractional Flow Reserve (FFR) is currently the gold standard for lesion physiology assessment; however, it's invasive and expensive. Other modalities, such as Quantitative Flow Ratio (QFR) and Instantaneous Wave-Free Ratio (iFR), can also determine the functional repercussion of coronary stenosis less invasively.

Hypothesis:
The results of FFR, iFR, and QFR of the same lesion, obtained during the same PCI, demonstrate the significant diagnostic capability of iFR and QFR, compared with FFR.

Methods:
Retrospective and unicentric study with stable chronic heart disease patients who underwent PCI. For every angiographic lesion, FFR, iFR and QFR were realized during the PCI. QFR was performed by an X-ray technician, blinded to the FFR and iFR results. A descriptive analysis was performed, as well as a correlation between the three measurements with Pearson’s r, chi-square, and ROC curve; and Bland-Altman plot for the results of FFR and QFR.

Results:
Thirty-six lesions of 27 patients were analyzed. For FFR, stenosis was considered significant when the result was <0.80, obtaining 17 lesions (52%) as significant; for iFR, it was <0.89, obtaining 14 significant lesions (38%); and for QFR, it was <0.85, resulting in 19 (52%) significant lesions. Considering that FFR is the actual gold standard, a ROC curve was used to analyze QFR, were the best cutoff value was 0.88 with a sensitivity of 88% and specificity of 64% (AUC of 0.86, 95% CI 0.736- 0.991, p<0.001), while for iFR the best cutoff value was 0.90 with a sensitivity of 82% and specificity of 74% (AUC of 0.85, 95% CI 0.722-0.984, p<0.001). Pearson’s r revealed a significant correlation between FFR-iFR (r=0.6, p<0.001), FFR-QFR (r=0.58, p<0.001), and QFR-iFR (r=0.62, p<0.001). Bland-Altman plot showed no significant difference between the data obtained with FFR and QFR. Chi-square test determined (p<0.001) that the three angiographic methods had a good correlation in determining whether a lesion was significant.

Conclusion:
The study demonstrated the significant diagnostic capability that the QFR and iFR methods have, when compared against the current gold standard FFR.
Abstract 12143: Hearing is Believing: A Case of a Ruptured Sinus of Valsalva Aneurysm
Authors: Murphy Sean P , Suero-Abreu Giselle A , Paine Adam N , Cameron Duke E , Learn Christopher P , Bloom Jordan P , Defaria Yeh Doreen
Published: December 2023

A 36-year-old previously active and healthy male was referred to our Adult Congenital Heart Disease clinic with worsening exertional dyspnea and intermittent palpitations over the past 6 months. He had recently been diagnosed with a membranous ventricular septal defect (VSD) and membranous septal aneurysm at another hospital, although images were not available for review.On physical exam, a continuous cardiac murmur was noted which prompted reconsideration of the diagnosis, with highest suspicion of ruptured sinus of Valsalva aneurysm (SVA). An urgent cardiac CT was obtained, which showed a large, mobile right SVA protruding into and partially obstructing the right ventricular outflow tract (RVOT), with pulmonic regurgitation and dynamic closure of a supracristal VSD (Figure 1A). A margin of the SVA was ill-defined and suspicious for rupture, although no definite communication was seen. An expedited TTE showed findings consistent with SVA rupture (Figure 1B), and he was admitted for surgery soon thereafter. Intra-operatively (Figure 1C), SVA rupture into the RVOT was confirmed by direct inspection; the SVA tissue was resected, the defect closed with a fresh autologous pericardial patch, and the VSD was closed with pledgeted sutures. Post-operatively, there was no leakage around the patch margin and only trace aortic regurgitation.A ruptured SVA causes continuous shunting from the aorta into an adjacent cardiac chamber and if left unrecognized, can lead to right heart failure, arrhythmia, and potentially sudden death, emphasizing the need for early identification. Echocardiography may show an aneurysmal sinus of Valsalva with a continuous (with accentuation in diastole) high-velocity, turbulent flow-jet into an adjacent cardiac chamber, and holodiastolic aortic flow reversal; a VSD is often present. Cross-sectional imaging is also important for diagnosis and surgical planning. A comprehensive physical exam is crucial to mitigate the risk of misdiagnosis.
Abstract 12144: The Association Between High Cardiac Index and Mortality
Authors: Zeder Katarina , Johnson Shelsey W , Lee Laurel Y , Qi Wei , Oldham William M , Kovacs Gabor , Opotowsky Alexander , Tedford Ryan J , Brittain Evan L , Maron Bradley A
Published: December 2023

Background:
Elevated cardiac index (CI) is implicated in the pathophysiology of heart failure. However, data on the CI hemodynamic spectrum that is associated with adverse outcome are lacking. We hypothesized that elevated CI is associated with increased mortality in patients referred for right heart catheterization (RHC).

Methods and Results:
We retrospectively assembled data for patients undergoing RHC at Vanderbilt University (1998-2013) with
≥
1 yr follow-up, excluding patients with low CI (<2.2 L/min/m
2
) which is known to be associated with increased mortality (N=2,548; age median 60 IQR [50-69] yrs; male, 50%; body mass index [BMI], 29 [25-35] kg/m
2
). Univariate Cox-regression was used to assess the association between CI (measured by thermodilution) octile and all-cause mortality (N=925 [36%] events, time to event 4.7 [3.1-8.8] yrs). All-cause mortality was 31% higher in the highest CI octile (N=317; 4.1 [3.9-4.7] L/min/m
2
; HR=1.31 [95%CI: 1.01-1.71], P=0.046) compared to the CI octile with lowest mortality risk (N=311; 3.1 [3.0-3.2] L/min/m
2
). Patients with CI >4.1 L/min/m
2
were younger (54 [46-63] vs. 60 [49-67] yrs, P<0.001) and had lower BMI (28 [24-34] vs. 31 [26-36] kg/m
2
, P<0.001), pulmonary vascular resistance (1.4 [0.9-2.4] vs. 1.8 [1.3-2.7] WU, P<0.001), and hemoglobin (11.9 [10.3-13.7] vs. 12.7 [11.1-13.8] g/dL, P=0.003); similar mean pulmonary arterial pressure (27 [19-35] vs. 26 [20-36] mmHg, P=0.556), pulmonary arterial wedge pressure (13 [8-18] vs. 13 [9-18] mmHg, P=0.352), frequency of hemodialysis (11% vs. 9%, P=0.259) and hyperthyroidism (2% vs. 1%, P=0.491); but significantly higher frequency of liver cirrhosis (18% vs. 7%, P<0.001) compared to the low risk CI group. The mortality association for CI >4.1 L/min/m
2
remained significant after adjusting for age, sex, liver cirrhosis and hemodialysis (HR 1.34 [95%CI 1.03-1.76], p=0.032).

Conclusion:
Cardiac index >4.1 L/min/m
2
is associated with a significant increase in all-cause mortality among patients referred for RHC, even after adjusting for established risk factors for high-output heart failure. These data expand the mortality continuum related to CI and support further studies that clarify the clinical phenotype of at-risk patients.
Abstract 12147: Flow-Induced Cellular Reprogramming in Mouse Atherosclerosis Model
Authors: Park Christian , Villa-Roel Nicolas , JEONG KIYOUNG , Baek Kyung In , Kim Yerin , Andueza Aitor , Zepeda Hector , Chou Amy , Kumar Sandeep , Kang Dong-Won , Jo Hanjoong
Published: December 2023

Introduction:
Atherosclerosis, a leading cause of death worldwide, is a chronic inflammatory disease that occurs preferentially in the arterial regions exposed to disturbed flow (d-flow), while those exposed to stable flow (s-flow) are protected. Recently, we reported d-
F
low
I
nduced
R
eprogramming of
E
ndothelial cells (ECs) (
FIRE
), including endothelial inflammation, endothelial-to-mesenchymal transition (EndMT) and endothelial-to-immune-cell transition (EndIT).

Hypothesis:
D-flow plus hypercholesterolemia (HighChol) exacerbates reprogramming of arterial cells leading to atherosclerosis development compared to d-flow alone and HighChol alone.

Methods:
To test this hypothesis, we induced atherosclerosis in C57BL/6 mice by an AAV-PCSK9 injection and high-fat diet to induce HighChol and/or partial carotid ligation (PCL) surgery to expose left carotid artery (LCA) to d-flow compared to the right CA (RCA) exposed to s-flow. Single cells prepared from collagenase digestion of the LCAs and RCAs at 2 and 4 weeks post-PCL were analyzed by scRNA-seq and integrated with our prior scRNA-seq data obtained at 2 days and 2 weeks post-PCL under normal blood cholesterol levels.

Results:
Overall, our data showed that d-flow was the most predominant regulator of arterial cell characteristics while HighChol alone had relatively minor effects. In the RCA, homeostatic EC, smooth muscle cell (SMC), and macrophage (MΦ) clusters were dominant regardless of cholesterol levels. Additionally, for these cell types, we found clusters that increased in response to d-flow in the LCA, which further increased with HighChol and time. Surprisingly, diffusion map trajectory analysis revealed a clear convergence of transcriptomic profiles of EndIT ECs, SMC-derived foam cell SMCs, and foamy MΦs.

Conclusions:
These results suggest
FIRE
initiated by d-flow is exacerbated by HighChol. We also found that SMCs and MΦs transition toward proatherogenic phenotypes under d-flow, which is further exacerbated by HighChol. Furthermore, differential gene expression analysis showed that proatherogenic ECs, SMCs, and MΦs show common transcriptomic profiles, suggesting common set of genes and pathways that could be targeted as effective atherosclerotic therapeutics.
Abstract 12177: Quantitative Flow Ratio is a Great Predictor of Microvascular Obstruction in ST-Segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention
Authors: Xin Yanguo , Li Jiayu , Li Hongwei
Published: December 2023

Backgrounds:
Compare the predictive effects of ST-segment resolution (STR) and quantitative flow ratio (QFR) in the detection of MVO in STEMI patients after PCI.

Research Questions:
To investigate the efficacy of STR/QFR in the evaluation of MVO detected by CMR in STEMI after PCI.

Methods:
A prospective cohort study enrolled 208 consecutive patients with STEMI. The degree of STR post procedure and predischarge after reperfusion was calculated. QFR were measured according to the angiography, CMR was performed within median time 5 days after revascularization to determine MVO. Clinical factors were enrolled to predict the incidence of MVO.

Results:
The MVO/LV mass is 1.42±2.28 in 126 patients with MVO according to CMR, and the area under ROC curves (AUC) identified QFR is the best predictor (AUC: 0.784,
P
<0.001). Factors including QFR, STR, TIMI flow, CK-MB, cTnI, WBC, and HsCRP showed good predictive effects for the incidence of MVO (
P
<0.05). Except for peak cTnI, QFR (%) was the best predictor (AUC: 0.784,
P
<0.001) (
Figure 1
). A nomogram for predicting MVO was done (c-index: 0.894) (
Figure 2
). A significant correlation was observed between STR and various parameters (
P
<0.05), except for the correlation between predischarge STR and MVO/LV mass at 6 months. Predischarge STR has the best correlation with infarct size after the 6-month follow-up (
r
=-0.509,
P
<0.001) (
Figure 3
). Regression analysis indicated that postoperative STR (β=-0.248,
P
=0.007) was a significant predictor of MVO/LV mass (
Figure 3
).
Figure 4
further analyzed heart function from in-hospital CMR between different postoperative STR levels, and from 6 months CMR between predischarge STR subgroups. Higher STR predicted less cardiac injury and more ideal index of cardiac remodeling.

Conclusions:
In STEMI patients after PPCI, QFR demonstrated better predictive effect of the incidence of MVO than STR. Predischarge STR is closely related to infarct size and ejection fraction after 6-month follow-up.
Abstract 12178: Association Between QT Prolongation and Cardiovascular Mortality in Cancer Patients
Authors: Chan Cheng-Han , Liu Chih-Min , Chen Pei-Fen , Wu I-Chien , Yufeng Hu
Published: December 2023

Introduction:
The QT interval (QT) is a safeguard criterion to avoid detrimental arrhythmias. Cancer patients are vulnerable to QT prolongation. However, its prognostic impact on cardiovascular (CV) mortality in cancer patients is not clear.

Research questions:
Which is the best QTc formula to predict CV mortality in cancer patients? Whether a QT interval would be a suitable predictor for CV mortality in cancer patients?

Methods:
This retrospective observational cohort included adult cancer patients who had an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n=59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry.

Results:
The AUC of QTcB (0.70) for predicting CV mortality at 90 days was better than QTcFri and QTcFra (0.63 and 0.50). The AUC of QTcB (0.68) for predicting CV mortality at one year was also better than QTcFri and QTcFra (0.65 and 0.56).Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P= 0.02) and one year (1.006, P <0.01). Compared to those with QTcB <500ms, the patients with QTcB ≥500ms were older, had more comorbidities, and higher CV (1.74%), cancer (24.5%), and all-cause mortalities (32.5%) within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality.

Conclusions:
Rather than a long QT interval per se, comorbidities contributed to CV mortality and irreversible outcome in cancer patients.
Abstract 12184: Non-ST Segment Elevation Myocardial Infarction in Patients Admitted With Sepsis: A Comparison of Ischemia-Guided Strategy and Early Catheterization
Authors: alhalaseh saleh , Alziadin Nmair , Maraey Ahmed , T Raju Apoorva , Mann Sabrina A , Alwarawrah Zaid , Al Wahadneh Omar
Published: December 2023

Introduction:
Sepsis and Non-ST Segment Elevation Myocardial Infarction (NSTEMI) are common medical conditions that often coexist and can cause significant morbidity and mortality. The optimal management strategy for these patients remains unclear. The American Heart Association (AHA) recommends an ischemia-guided approach in patients with stable NSTEMI, but it is unknown if this strategy is beneficial in the setting of sepsis. The aim of this study was to evaluate the outcomes of an ischemia-guided strategy in patients with sepsis and NSTEMI who underwent left heart catheterization (LHC) and percutaneous intervention (PCI).

Methods:
This study utilized data from the National Inpatient Sample (NIS) from 2016-2020. Patients admitted with a principal diagnosis of sepsis and a secondary diagnosis of NSTEMI were included in the study. Patients with cardiogenic shock or STEMI were excluded from the study due to the necessity of urgent or emergent left heart catheterization. Patients were divided into two groups based on the timing of LHC & PCI, within 24 hours or 48-72 hours of admission. Logistic linear regression was used to adjust for multiple factors including patient demographics, hospital characteristics, and comorbidities.

Results:
A total of 298,855 patients were included in the analysis, with 48% of them being females and a mean age of 73 years. Patients who received an ischemia-guided strategy had lower mortality rates (OR: 0.45, 95% CI: 0.27-0.74, P=0.002) and a lower risk of heart failure exacerbation (OR: 0.74, 95% CI: 0.56-0.97, P=0.030) compared to those who did not receive this strategy. There was no significant difference in length of stay (Coefficient: 0.33, 95% CI: -0.34 - 1.01, P=0.330), cardiac arrest (OR: 0.08, 95% CI: 0.00-28.0, P=0.401), or gastrointestinal bleed (OR: 0.81, 95% CI: 0.49-1.33, P=0.412) between the two groups.

Conclusion:
This study suggests that an ischemia-guided strategy may be beneficial in patients with sepsis and NSTEMI compared to urgent percutaneous coronary intervention. The strategy was associated with lower mortality rates and a lower risk of heart failure exacerbation. Further studies are needed to confirm these findings and determine the optimal management strategy for this patient population.
Abstract 12234: Concurrent Amyloid Light-Chain Cardiac Amyloidosis and Abdominal Leiomyosarcoma - Diagnostic and Therapeutic Challenges
Authors: Arnold Joshua H , Merimsky Ofer , Shamai Sivan , Wolf Ido , Banai Shmuel , Topilsky Yan , Avivi Irit , Cohen Yael , Shragai Tamir , Laufer Perl Michal
Published: December 2023

Background:
AL amyloidosis is a rare disorder characterized by organ infiltration of unstable misfolded light chain proteins. Diagnosis requires a high degree of suspicion, and cardiac involvement has poor outcomes. Anthracycline-based regimens are preferred for treating abdominal leiomyosarcoma (LMS) but pose a challenge in the presence of cardiac AL amyloidosis.

Case:
A 66-year-old male presented with bilateral leg edema and underwent evaluation for new heart failure. Echocardiography revealed preserved left ventricle ejection fraction (LVEF) with mild hypertrophy, increased interventricular septum thickness, and diastolic dysfunction. Due to concern for cardiac amyloidosis, the patient underwent nuclear scintigraphy scan, which was negative. Ongoing clinical suspicion prompted endomyocardial biopsy, which was positive for Congo Red staining, and serum studies revealed monoclonal lambda spike with increased free light chains. PET-CT was done to assess the lung nodule, revealing abdominal LMS. While Anthracycline is the drug of choice for LMS, its potential cardio-toxic effect in the presence of heart failure need be addressed. Treatment decisions involved a multidisciplinary team, resulting in bortezomib for AL amyloidosis, gemcitabine/paclitaxel for LMS, and symptomatic heart failure management.

Decision-making:
Anthracycline therapy was avoided due to potential cardiotoxicity. Daratumumab was added to expedite light chain reduction and minimize cardiotoxic effects. Individualized treatment considered the patient's clinical presentation and comorbidities.

Conclusion:
Diagnosing cardiac amyloidosis requires a high index of suspicion. Concurrent AL amyloidosis and LMS is extremely rare and presents a therapeutic dilemma, necessitating personalized management. Further research is needed to assess the potential cardio-toxic effect of anthracycline in the presence of cardiac AL amyloidosis.
Abstract 12241: Low-Efficiency Gene Editing is Capable of Suppressing Arrhythmogenesis in Long QT Syndrome Type II: Computer Simulation Study
Authors: Navarrete-Welton Allison , Kim Tae Yun , Bronk Peter , Qu Zhilin , Koren Gideon , Choi Bum-rak
Published: December 2023

Background:
Long QT Syndrome Type II (LQT2) is a congenital cause of arrhythmia and sudden cardiac death due to mutations in ion channel hERG responsible for the rapid inward rectifying potassium current (I
Kr
). Progress in gene therapy may result in a viable treatment for LQT2. However, the gene transduction efficacy required to prevent cardiac arrhythmias in LQT2 is unknown. We used computer simulation to examine the minimum gene transduction efficacy necessary to suppress early afterdepolarizations (EADs).

Hypothesis:
Low transduction efficacy of hERG is sufficient to suppress EADs through electrotonic coupling between transduced I
Kr
(+) and non-transduced I
Kr
(-) cardiomyocytes (Fig 1A).

Methods:
Computational models of rabbit and human cardiac tissue were implemented in 2D (100 x 100 cells) and 3D (13 x 13 x 13 cells) with a multi-state Markov model for I
Kr
and a dynamic gap junction resistance model. Gene transduction efficacy was modeled by varying the percentage of I
Kr
(+) cardiomyocytes from 0-100%. Spatial heterogeneity in gene delivery was modeled by varying the cluster size of I
Kr
(+) cells from 1-400 cells. I
Kr
(+) cell clusters were distributed randomly in the tissue.

Results:
In 2D, EADs were suppressed with 14% I
Kr
(+) cells (rabbit model) and 12% I
Kr
(+) cells (human model) (Fig 1B). In 3D, the minimum transduction efficacy was further reduced to 10% (rabbit model) which likely reflects the impact of increased cell-cell coupling. Clustering I
Kr
(+) cells required greater transduction efficacy (Fig 1C). Detailed ionic current trajectory analysis suggests that the sufficiently large gap junction current from I
Kr
(+) cells during phase 2 of the action potential can prevent I
Kr
(-) cells from undergoing the Andronov-Hopf bifurcation that leads to EADs.

Conclusions:
Computational models suggest low-efficiency gene editing is a viable approach for suppressing arrhythmogenesis in LQT2 patients.
Abstract 12244: Gender Differences in Leadless Pacemaker Peri-Procedural Adverse Events, Long-Term Device Functions, and Clinical Outcomes
Authors: Huang Jingwen , bhatia neal , Lloyd Michael S , Westerman Stacy , Shah Anand , Leal Miguel A , Delurgio David B , Patel Anshul , Tompkins Christine , Leon Angel R , El-Chami Mikhael F , Merchant Faisal M
Published: December 2023

Introduction:
Some studies suggested gender differences in procedural complication rates and long-term outcomes for trans-venous pacemakers. Little is known about gender differences associated with leadless pacemaker (LP) implantation.

Methods:
We reviewed all Medtronic Micra LP implants at our institution from 9/2014 to 9/2022. Device parameters (R wave sensing, impedance, and capture threshold), right ventricular pacing burden (RVP), left ventricular ejection fraction (LVEF), and 30-day adverse events post implant were obtained.

Results:
Among 489 patients, 50.9% were men. Mean follow-up was 1.7 ± 1.5 years. Women were older than men at the time of LP implant (78.1 ± 14.7 vs 75.5 ± 15.3 years old, p=0.04). There were no significant differences in R wave sensing and RVP between genders. Impedance and LVEF were higher in women and capture thresholds were higher in men at both baseline and last follow up. Despite significant differences in device parameters between genders, differences were small and not clinically relevant in most cases (Figure). Mean number of device deployments required at implant was similar: women 1.3 ± 0.6 vs men 1.4 ± 0.9, p=0.16). Implant related complications were similar between women and men: access site hematoma (5 vs 9, p=0.42), pseudoaneurysm (0 vs 2, p=0.49), cardiac perforation (2 vs 1, p=0.62), 30-day re-hospitalization (16 vs 25, p=0.19) and 30-day mortality (16 vs 17, p=0.99). LVEF decreased over time in both genders (Figure). During follow-up, 4 women and 6 men required transvenous cardiac resynchronization therapy (CRT) implantation (p=0.75) and 4 women vs 2 men required transvenous dual chamber pacemaker implantation (p=0.44).

Conclusion:
Outcomes of leadless pacemaker implantation are similar between women and men. Long-term device function is excellent in both genders. However, about 3% of all patients required device upgrade, highlighting the need for close electrophysiology follow-up after LP implant in both genders.
Abstract 12251: Impact on Effectiveness of Carvedilol and Bisoprolol for Patients With Heart Failure Aged 80 Years Old and Older
Authors: Higashi Kensaku
Published: December 2023

Background:
Heart failure remains a cause of significant mortality and morbidity. Multiple trials have shown the effects of both Carvedilol and Bisoprolol in treatment of heart failure. However, there are few reports that which is more effective for elderly patients.

Objective:
We investigate retrospectively the effectiveness of Carvedilol and Bisoprolol in reducing all-cause death and readmission due to worsening of disease condition in patients with heart failure aged 80 years old and older.

Methods and Results:
604 consecutive patients over the age of 80 were enrolled who were admitted by acute heart failure in our hospital from July 2012 to December 2018. We evaluated the incident rate of clinical events by group treated with Carvedilol and Bisoprolol compared to group with no β-blocker treatment. The clinical events were defined as all-cause death and readmission by worsening of acute heart failure. In low LVEF group (LVEF<50), Kaplan-Meyer methods analysis showed that there were no significant differences between three groups (Bisoprolol, Carvedilol and no beta-blocker). But, in high LVEF group (LVEF>50), Bisoprolol and Carvedilol significantly increased the incident rate of clinical evets for the patients with HF compared with no β-blocker (Bisoprolol: χ2=3.840, Logrank; p=0.05, Carvedilol: χ2=5.443, Logrank; p=0.02).Cox proportional hazard analysis revealed that Bisoprolol and Carvedilol were significant risk factors associated with the adverse clinical events (Carvedilol: Hazard Ratio=1.538, 95% CI; 1.060-2.231: p=0.023, Bisoprolol: Hazard Ratio =1.427, 95% CI; 1.000-2.036: p=0.050).

Conclusions:
Carvedilol and Bisoprolol significantly increased the incident rate of clinical events in HFpEF with aged 80 years old and older. Beta-blocker therapy for these patients may be harmful. Recent advances in heart failure treatment have led to the need for further evaluation of the introduction and use of beta-blockers in heart failure treatment.
Abstract 12278: A Case of Hereditary Transthyretin Amyloidosis Caused by a Rare Mutation
Authors: Stinson Leah , Carter Spencer , Waldron Jill , Stehlik Josef , Godara Amandeep , Sideris Konstantinos , Brinker Lina , Mooney Ryan
Published: December 2023

Introduction:
Transthyretin amyloidosis (ATTR) is an underdiagnosed multisystem disease caused by dissociation of the tetrameric structure, misfolding, and deposition of the protein transthyretin. More than 100 known mutations that decrease the stability of transthyretin have been implicated in hereditary ATTR (ATTRv). Organ tropism and disease progression can vary significantly depending on the specific mutation, though cardiomyopathy and neuropathy are the most common phenotypes (Figure 1b). Reproducibly tracking the pattern of end organ dysfunction in ATTRv caused by novel mutations may help elucidate the mechanism of mutation-specific organ tropism and predict the potential disease course for patients with the same mutation.

Case:
The index patient is an 86-year-old male with a history of atrial fibrillation, tachy-brady syndrome requiring a pacemaker, orthostatic hypotension, peripheral neuropathy, and left ventricular hypertrophy (interventricular septum 1.4 cm prior to diagnosis) on echocardiogram. The constellation of symptoms raised the clinical suspicion for amyloidosis which was confirmed on endomyocardial biopsy. Given his age, he was presumed to have wild type ATTR by the local team. Upon referral to our center, genetic testing was performed which revealed the missense mutation c.229G>A which results in the amino acid substitution p.Gly77Arg, and has previously only been reported in one patient in Sweden. We initiated family screening and identified multiple family members with the mutation with varying phenotypes including no symptoms, cardiomyopathy, and neuropathy (figure 1a).

Discussion:
We identified a family with a rare c.229G>A mutation, and report on a mixed cardiomyopathy and neuropathy phenotype. Our report highlights the importance of screening for pathologic genetic variants in all patients with a diagnosis of ATTR given the treatment and prognostic implications for patients and their family members.
Abstract 12281: Association Between Extremely High HDL-C Levels and Mortality: A Systematic Review and Meta-Analysis
Authors: Mamede Isadora , Antonio Pinheiro Braga Marcelo , Oliveira Franchini Anne Estefane , Martins Otavio C , Silveira Filho Rodrigo B , Catao Marcel
Published: December 2023

Background:
Recent research challenges previous findings that linked higher levels of high-density lipoprotein cholesterol (HDL-C) to lower cardiovascular (CV) mortality. New evidence suggests that extremely high HDL-C may increase the risk of adverse CV outcomes.

Research Question:
What is the relationship between very high levels of HDL-C and mortality in patients without coronary artery disease (CAD)?

Goal:
To perform a meta-analysis of the association between extremely high HDL-C and mortality endpoints in patients without CAD.

Methods:
We systematically searched PubMed, Embase, and Cochrane for studies comparing very high (≥80 mg/dL) HDL-C levels to normal (40-60 mg/dL) levels in individuals without CAD. Heterogeneity was examined using I2 statistics, and a random-effects model was employed. Review manager 5.4 was used for statistical analyses.

Results:
Among 1,044,699 patients without CAD from 7 studies, 88,676 (8.5%) had very high HDL-C levels, and 535,742 (51.3%) had normal HDL-C levels. Overall, there was no significant difference in all-cause mortality between the groups (OR 0.93; 95% CI 0.86-1.00; p=0.06). However, stratified by sex, very high HDL-C levels were associated with a significantly higher all-cause mortality in men (OR 1.30; 95% CI 1.01-1.67; p=0.04; Figure 1A) and a significantly lower all-cause mortality in women (OR 0.85; 95% CI 0.77-0.93; p=0.0005; Figure 1A) (p=0.002 for interaction). CV mortality was significantly lower in patients with very high HDL-C (OR 0.82; 95% CI 0.71-0.93; p=0.002), although again there was a significant interaction (p=0.0004) between women (OR 0.73; 95% CI 0.62-0.85; p=0.0001; Figure 1B), in whom high HDL-C was protective, and men (OR 1.34; 95% CI 0.99-1.80; p=0.06; Figure 1B).

Conclusions:
These findings indicated that very high levels of HDL-C (≥ 80 mg/dL) are associated with increased mortality in men, but lower mortality in women.
Abstract 12302: Interleukin-22 Deficiency Exacerbates Right Ventricular Remodeling and Tricuspid Regurgitation During Pressure Overload
Authors: Shibao Kodai , Yasukawa Hideo , Daiki Akagaki , Okabe Kota , Yanai Toshiyuki , Kanako Shima , Fukumoto Yoshihiro
Published: December 2023

Introduction:
Right ventricle (RV) remodeling is associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in left ventricular remodeling after acute myocardial infarction; however, the role of IL-22 in the development of RV remodeling remains elusive.

Hypothesis:
IL-22 would inhibit the development of RV remodeling during pressure overload.

Methods:
Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band> 25 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Four weeks after PAB, RV function was measured by echocardiography, and 2 weeks after PAB, real-time PCR analysis was performed to measure IL-22 receptor subunit alpha 1 (IL-22RA1), and endogenous IL-22 inhibitor IL-22 binding protein (IL-22BP).

Results:
Four weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/BW: 1.4±0.2% vs 1.7±0.2%, P=0.047). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 4 weeks safter PAB. Compared with wild type mice, IL-22 KO mice had reduced TAPSE (0.64±0.11mm vs. 0.47±0.06mm, P=0.002) and FAC (30.6±6.6% vs. 23.5±4.4%, P=0.019), whereas RVEDV was increased (12.8±2.2mm
2
vs. 17.1±2.5mm
2
, P=0.019). Four weeks after PAB, the frequency of tricuspid regurgitation (TR) in IL-22 KO mice was significantly higher than that in wild type mice (100% vs 30%, P=0.004). The expression of IL-22, IL-22RA1 and IL-22BP in the RV tended to increase 2 weeks after PAB (wild-type mice with PAB (n=3) vs. wild-type mice with sham; IL-22RA1: 1.489 vs 1.773, P=0.175, IL-22BP: 0.025 vs 0.067, p=0.005).

Conclusions:
These results suggest that IL-22 may play a preventive role in the development of RV remodeling and TR during pressure overload.
Abstract 12321: Discordant Association of Nonalcoholic Fatty Liver Disease With Lipoprotein(a) and Markers of Atherogenic Dyslipidemia
Authors: Lee Terence , Grandhi Gowtham R , Alebna Pamela , Asgharpour Amon , Dixon Dave L , Salloum Fadi N , Sanyal Arun J , Siddiqui Mohammad , Mehta Anurag
Published: December 2023

Background:
Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia and an increased risk of cardiovascular events. Previous studies have suggested a paradoxical inverse relationship between NAFLD severity and Lp(a) level, an independent cardiovascular risk factor. However, contemporary data in patients with biopsy-proven NAFLD in the U.S. are lacking.

Hypothesis:
NAFLD severity on liver biopsy has a discordant association with Lp(a) and other markers of atherogenic dyslipidemia.

Methods:
Lp(a), traditional lipid profile, apolipoproteins, and nuclear magnetic resonance-based lipoprotein particle concentration were measured in 151 patients with NAFLD. Levels were compared between those with nonalcoholic fatty liver (NAFL) on histology and non-alcoholic steatohepatitis (NASH), the clinically aggressive NAFLD variant.

Results:
Median age was 55 [48, 62] years, 67% of patients were women, 83% were White, 43% had NAFL, and 57% had NASH. Demographic characteristics were similar among those with NAFL and NASH. Triglyceride level was higher and High-Density Lipoprotein-cholesterol (HDL-C) was lower among those with NASH as compared with NAFL. Circulating concentration of two key markers of atherogenic dyslipidemia, Apolipoprotein-B (apoB) and Low-Density Lipoprotein particle concentration (LDL-P) was 9% and 17% higher in the NASH group as compared with NAFL, respectively. Contrastingly, Lp(a) concentration was 50% lower in NASH relative to NAFL group (Figure). Hepatocyte ballooning, lobular inflammation, and fibrosis on histology were inversely associated with Lp(a) concentration, while steatosis severity was not.

Conclusions:
NAFLD severity has a discordant association with Lp(a) and markers of atherogenic dyslipidemia. The mechanistic basis of this relationship may have implications for prognosticating cardiovascular disease risk and determining the safety of targeted Lp(a) lowering in patients with NAFLD.
Abstract 12323: Cardiovascular Mortality Prediction Depends on the Time Point of Blood Pressure Measurement Rather Than on the Use of European versus US Blood Pressure Categorizations
Authors: Leiherer Andreas , Brozek Wolfgang , Muendlein Axel , Ulmer Hanno , Saely Christoph H , Plattner Thomas , Vonbank Alexander , Mader Arthur , Sprenger Lukas , Maechler Maximilian , Larcher Barbara , Fraunberger Peter , Nagel Gabriele , Zitt Emanuel , Drexel Heinz , Concin Hans
Published: December 2023

Introduction:
Blood pressure (BP) is a predictor of cardiovascular risk but it changes during lifetime.

Hypothesis:
We hypothesize that there are differences in the value of systolic and diastolic blood pressure (BP) at different stages of life for predicting cardiovascular mortality risk, an issue which was addressed in this observation study (OS).

Methods:
At the baseline of the OS, BP was measured in 1497 cardiovascular disease patients at a median age of 65 years, and their outcome was recorded over 21 years. Fifteen years prior to the OS, the identical patients had participated in a health survey (HS) comprising BP measurement. The value of earlier (HS) vs. recent (OS) BP measurements for risk prediction was addressed using both guideline-defined BP categorizations from Europe (ESC/ESH) and the US (ACC/AHA).

Results:
BP at HS was a significantly better predictor of cardiovascular mortality than BP at OS (NRIESC/ESH=0.29, p<0.001; NRIACC/AHA=0.30, p<0.001). Each 10mm Hg increase was significantly positively associated with cardiovascular mortality for both systolic and diastolic blood pressure (HR=1.17 [1.11-1.23] and 1.20 [1.09-1.32], respectively) when measured at HS. In contrast, regarding systolic BP recorded at OS, the significant association with cardiovascular mortality (HR=1.04 [0.98-1.10]) was abrogated, and with diastolic BP the association has reversed (HR=0.82 [0.74-0.92]. In contrast, ESC/ESH and ACC/AHA BP categorizations were comparably valuable predicting cardiovascular mortality (NRIHS=0.04, p=0.563; NRIOS=0.02, p=0.817).

Conclusions:
Irrespective of categorization differences between European and US BP guidelines, earlier-in-life BP readings are valuable risk predictors for cardiovascular mortality and they outperform BP readings done at a more advanced age.
Abstract 12346: Atherosclerotic Cardiovascular Disease Risk Associated With Social Determinants of Health at Individual and Area Levels
Authors: Xia Mengying , An Jaejin , Safford Monika M , Colantonio Lisandro , Muntner Paul , Reynolds Kristi , Moran Andrew E , Zhang Yiyi
Published: December 2023

Introduction:
Adverse social determinants of health (SDOH) are associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if the ASCVD risks associated with area-level SDOH are similar to those with individual-level measures. Further, SDOH are not included in the Pooled Cohort Equations (PCEs) when estimating 10-year ASCVD risk. Studies have shown that PCEs systematically underestimate risk for socially deprived individuals.

Aims
To examine the association of individual- and area-level SDOH including education, income, and employment with incident ASCVD. Also, we assessed if adding SDOH to the PCEs improves risk prediction accuracy.

Methods:
We pooled data from four cohorts: Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, Framingham Heart Study Offspring Cohort, and Reasons for Geographic and Racial Differences in Stroke Study. We excluded participants with a history of ASCVD. Individual-level SDOH were based on participants’ self-report and area-level SDOH were derived by linking participants’ addresses to US Census tract data. We used Cox proportional hazards models to assess the associations between SDOH and ASCVD. We also assessed the changes in discrimination (Harrell’s C-index) and calibration (Integrated Brier Score) after adding SDOH to risk prediction models.

Results:
We analyzed data from 27,603 participants (mean age 61.4 years, 59% women, and 49% White). During a median follow-up of 13 years, 2,839 incident ASCVD events occurred. Both individual- and area-level SDOH were associated with ASCVD (
Figure, Panel A
). Adding both individual- and area-level SDOH to risk prediction modestly improved model discrimination and calibration in Black men and women (
Figure, Panels B & C
), and also improved calibration in non-Black women.

Conclusions:
The findings suggest that SDOH may be considered in the development of future ASCVD risk assessment tools, particularly among Black individuals.
Abstract 12360: Association of Coagulation Factor XI Levels With Cardiac Function and Cardiovascular Events: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ji Yuekai , Zhang Michael J , Wang Wendy , Norby Faye L , Van't Hof Jeremy R , EATON ANNE , Alonso Alvaro , Solomon Scott , Shah Amil M , Chen Lin Y
Published: December 2023

Introduction:
Coagulation Factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study showed that FXI has an anti-fibrotic role that ameliorated diastolic dysfunction and heart failure (HF). Whether FXI levels are associated with cardiac function and cardiovascular (CV) events in humans is unknown.

Hypothesis:
We hypothesize that lower FXI levels are associated with worse cardiac function and higher risk of CV events (HF and atrial fibrillation [AF]).

Methods:
We included 4,471 participants (mean age 75 years, 57% female, 17% Black) who attended ARIC Visit 5 (2011-2013) with plasma FXI measured by Somalogic and cardiac function measured by echocardiography. HF and AF events were ascertained through 2019. Linear regression was used to assess the association between FXI and cardiac function measures. Logistic regression and Cox proportional hazard model were used to examine the association of FXI levels with prevalent and incident HF and AF, respectively.

Result:
At baseline, there were 665 and 419 participants with prevalent HF and AF; over a median follow-up of 7 years, there were 643 and 415 incident HF and AF events. Among cardiac function measures, we found significant associations between FXI level and E/A ratio, left atrial (LA) volume index, LA reservoir strain, and LA contractile strain, but not E/e’ ratio, LA conduit strain, left ventricular (LV) ejection fraction or LV global longitudinal strain (Table). Lower FXI levels was associated with a higher odds of prevalent AF but not prevalent HF (Table). No significant associations were found between FXI levels and incident HF or AF.

Conclusion:
Lower FXI levels are associated with worse diastolic function, LA function and size, and prevalent AF, but not LV systolic function, prevalent HF, or incident HF or AF. More research is needed to assess unwanted effects of FXI inhibition on cardiac function and risk of CV events.
Abstract 12413: Arrhythmia Burden, Associated Outcomes, and Cost Implications in Patients Hospitalized With Idiopathic Pulmonary Fibrosis
Authors: Benjamin Patrick , Oyenubi Olamide , Gitler Bernard , Stan Andreea-Constanta , ROBLES JULIAN
Published: December 2023

Introduction:
Arrhythmias are a common cardiovascular manifestation of idiopathic pulmonary fibrosis (IPF), however, associated costs and hospital outcomes are unknown. We aim to determine the impact of cardiac arrhythmias on outcomes and costs among hospitalized IPF patients.

Methods:
A retrospective cohort analysis was conducted using the National Inpatient Sample from 2017-2019. IPF-associated hospitalizations with and without concurrent arrhythmia were compared and identified by appropriate ICD-10 CM codes. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were the duration of hospitalization and associated costs.

Results:
Among 92,125 IPF patients, 28.5% (n=26,235) were diagnosed with 29,885 arrhythmias. The most frequent (65%) form of arrhythmias was atrial tachyarrhythmias of which atrial fibrillation was the most predominant (88%). The frequency of bradyarrhythmias, ventricular tachyarrhythmias, and unspecified arrhythmias were 10%, 8%, and 17%, respectively. The IPF-arrhythmia group was predominantly male (64% vs 36%, P < 0.001) and significantly older (76 vs 69 years, p<0.001) with a higher number of comorbidities (3 or more Charlson comorbidity index score: 52% vs 40%, p<0.001). All-cause mortality was significantly higher in the IPF-arrhythmia cohort (12.3% vs. 9.5%, p<0.001) and the odds of in-hospital death remained significantly higher among the IPF-arrhythmia cohort after adjusting for sociodemographic and hospital-level factors (AOR 1.30, 95% CI 1.17-1.44, P <0.001). The hospital length of stay was longer (8.4 vs. 6.7 days, p<0.001), and costs were higher ($123,185 vs. $88,073, p<0.001) among the IPF-arrhythmia cohort.

Conclusions:
Concurrent arrhythmias are associated with worse survival outcomes and costs for patients with IPF. Future studies are needed to confirm the benefits of treatment and elucidate the appropriateness and cost-effectiveness of screening for arrhythmias among IPF patients.