bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12316: Association of State Medicaid Expansion With Incidence of Gestational Diabetes Mellitus Among Nulliparous Individuals in the US, 2012-2019
Authors: Everitt Ian , Venkatesh Kartik , Harrington Katharine , Carnethon Mercedes R , OBrien Matthew , GROBMAN William , Pool Lindsay , Khan Sadiya S
Published: June 2023

Introduction:
The frequency of GDM and pregnancy-related complications of GDM are increasing in the United States. Detection and treatment are important to manage GDM and reduce the risk of pregnancy-related complications. The objective of this analysis was to assess whether expanding Medicaid, a state-level policy change that enhances access to care, was associated with changes in rates of GDM and outcomes among those with GDM.

Methods:
Data from nulliparous individuals aged 20-44 years with a first live birth from 30 states between 2012-2019 were included from the National Center for Health Statistics. The primary outcome, age-standardized incidence of GDM, was compared between Medicaid expansion states (N=16) and Medicaid non-expansion states (N=14) using a quasi-experimental analysis with difference-in-differences (DID) models. DID models utilized multivariate linear regression with random intercepts for state (to adjust for unobserved state-level fixed effects), fixed effect for year, and adjustment for state-level covariates including demographics, and health and economic indicators. Secondary outcomes included GDM complicated by preterm birth (≤36 weeks) and high (>4000 grams) or low (<2500 grams) birthweight infants.

Results:
Among 7,502,838 individuals, age-standardized rates of GDM increased in both Medicaid expansion (49.3 to 56.8 per 1000 births) and non-expansion states (48.6 to 52.7 per 1000 births). Expansion status was associated with a greater increase in rates of GDM (DID +4.32 [95% CI, +1.73 to +6.92] per 1000 births; Figure). Among individuals with GDM, rates of having a preterm birth or a high or low birthweight infant were not significantly different in expansion relative to nonexpansion states.

Conclusions:
Between 2012-2019, states that expanded Medicaid had a significantly greater increase in incidence of GDM. However, among those with GDM, rates of preterm birth and high or low birthweight did not differ by expansion status.
Abstract 12317: Improving Prenatal Detection of Heart Disease Scalable Composite Analysis of Six Fetal Cardiac Biometrics
Authors: Reddy Aneela , Rizvi Sara , Chinn Erin , Athalye Chinmayee , Moon-Grady Anita J , Arnaout Rima
Published: June 2023

While prenatal congenital heart disease (CHD) screening has improved, accuracy remains as low as 30 percent. Standard fetal biometrics—cardiac axis (CA), cardiothoracic ratio (CTR), RV fractional area change (FAC), LV FAC, RA:LA area ratio, RV:LV area ratio—are available from screening imaging and can each aid in CHD screening, but can be cumbersome to measure. Combinations of biometrics may offer further utility but are challenging to integrate at the point of care. We tested whether using these biometrics in combination has utility in CHD screening (normal vs. abnormal). Further, we tested whether automatically predicted biometrics could function similarly to manually-labeled biometrics for this purpose. We included 105 fetal echocardiograms (20 normal, 85 abnormal across 12 different CHD lesions). We manually calculated the six biometrics above, performed dimensionality reduction using principal component analysis, and then clustered the resulting data by K-means. A previously developed deep learning model (Arnaout et al Nature 2021) was also used to automatically predict biometrics for normal, tetralogy of Fallot, and hypoplastic left heart syndrome hearts and plotted on the above cluster map. Optimal number of clusters was four, with RV:LV ratio and CTR as the most important features distinguishing clusters. Cluster 1 was predominantly normal hearts with cluster 2-4 largely abnormal hearts (Figure 1). The sensitivity and specificity for predicting abnormal hearts (e.g. CHD) was 86% and 75%, respectively. Model-predicted biometrics landed in the same clusters as the manually labeled lesions (Figure 1). To our knowledge, this is the first use of clustering to provide visualization of multiple fetal cardiac biometrics at once and reveal diagnostic utility. Once tested in screening ultrasounds on a larger scale, clustering of automated biometrics may be clinically useful at the screening point of care to augment scalable population-based screening.
Abstract 12404: Assessment Of Associations Between Hypoglycemia And Cardiovascular Outcomes In The Randomized CARMELINA And CAROLINA Trials Of The Antihyperglycemic Medication Linagliptin
Authors: Kolkailah Ahmed A , Marx Nikolaus , Rosenstock Julio , Johansen Odd Erik , Cooper Mark E , Alexander John H , Toto Robert , Wanner Christoph , Espeland Mark A , Mattheus Michaela , Schnaidt Sven , Perkovic Vlado , Gollop Nicholas D , McGuire Darren K
Published: June 2023

Introduction:
Bidirectional associations between hypoglycemia and cardiovascular (CV) outcomes were evaluated in 2 CV outcome trials of the DPP-4 inhibitor, linagliptin.

Methods:
CARMELINA and CAROLINA trials evaluated CV outcomes with linagliptin vs placebo or glimepiride, respectively, in adults with type 2 DM at high CV ± kidney risk; of the 2, CARMELINA was longer duration/higher risk cohort. The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3P-MACE), with heart failure (HHF) added to the primary outcome for the present analyses. Hypoglycemia was defined as plasma glucose <54 mg/dL; severe hypoglycemia defined as needing external help. Associations between the first hypoglycemic episode and subsequent CV events, and conversely, between non-fatal CV events (MI, stroke, HHF) and subsequent hypoglycemic episodes, were assessed using multivariable Cox proportional hazards models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode.

Results:
In CARMELINA, there was an association between hypoglycemia and subsequent 3P-MACE + HHF (adjusted HR: 1.23; 95% CI 1.04-1.46), and between non-fatal CV events and subsequent hypoglycemia (adjusted HR: 1.39; 95% CI 1.06-1.83). In CAROLINA, there was no significant association between hypoglycemia and subsequent 3P-MACE + HHF (adjusted HR: 1.00; 95% CI 0.76-1.32), nor between non-fatal CV events and subsequent hypoglycemia (adjusted HR: 1.44; 95% CI 0.96-2.16) (Fig). In analyses of CV events occurring within 60 days after hypoglycemia, in both trials, there was either no association observed or too few events to analyze.

Conclusion:
The observed bidirectional associations between hypoglycemia and CV outcomes in CARMELINA and no significant associations in CAROLINA challenge the notion that hypoglycemia causes adverse CV events, but rather suggest that both hypoglycemia and CV events identify vulnerable patients at risk for both.
Abstract 12413: Type 2 Diabetes Mellitus and Congestive Heart Failure in Women Are Mutually Independent Predictors of Non-alcoholic Fatty Liver Disease
Authors: Maechler Maximilian , Sprenger Lukas , Mader Arthur , Larcher Barbara , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: June 2023

Introduction:
Non-alcoholic fatty liver disease (NAFLD) is associated with both type 2 diabetes mellitus (T2DM) and congestive heart failure (CHF), and T2DM is highly prevalent in CHF patients, in particular among women. However, the single and joint associations of T2DM and CHF with NAFLD in women have not been investigated yet.

Hypothesis:
We hypothesize that congestive heart failure and T2DM are independent predictors of NAFLD in women.

Methods:
We investigated 76 female patients with CHF and 321 female controls who did not have signs or symptoms of CHF and in whom significant coronary artery disease was ruled out angiographically. The presence of NAFLD was determined using the validated fatty liver index (FLI).

Results:
The prevalence of T2DM was 39.5% in women with CHF and 22.1% in controls (p=0.002). FLI values and prevalence rates of NAFLD (FLI≥60) in non-CHF women without T2DM were 43±28 and 31.6%, respectively. They were significantly higher in non-CHF, but T2DM patients (65±28, p<0.001 and 64.8%, p<0.001, respectively), in CHF patients without T2DM (67±25, p<0.001 and 63.0%, p=0.002, respectively) and in CHF patients with T2DM (66±31, p<0.001 and 66.7%, p<0.001, respectively). In multivariate analysis of covariance, T2DM and CHF proved to be mutually independent predictors of FLI after adjustment for age, sex, BMI, LDL-C, history of smoking and hypertension and use of statins (F=7.25; p=0.007 and F=46.89; p<0.001, respectively); concordantly, T2DM and CHF independently predicted the presence of NAFLD in logistic regression analyses, with adjusted odds ratios of 3.22 [1.38-7.50]; p=0.007 and 21.71 [6.58-71.59]; p<0.001, respectively.

Conclusions:
We conclude that CHF and T2DM are mutually independent predictors of NAFLD in women.
Abstract 12441: Association Between Habitual Consumption of Meal Replacement Products And Cardiac Mortality Risk in US Adults: A Prospective Study
Authors: Zhao Yuxuan , Yang Haiming , Meng Xiao , Wang Yueqing , Song Mingyu , Sun Dianjianyi
Published: June 2023

Introduction :
Little is known about the long-term association between Habitual Consumption of Meal Replacement Products and the risk of cardiac mortality.

Methods:
Analyses were performed using data from NHANES 2003 to 2006 and linked mortality data, consisting of 5292 participants aged 20 to 84 years old. The frequency of MR consumption was categorized into 3 groups according to the food frequency questionnaire: seldom, often and almost every day. Linked cardiac mortality records from the National Death Index were documented till Dec 31, 2019. Cox regression models were fitted controlled for demographic characteristics, social-economic factors, disease histories, and lifestyle factors.

Results:
At baseline, the overall percentage of American adults consuming MR products often and almost every day were 10.39% and 3.34%. During a median follow-up of 10.75 years, 98 death events due to heart diseases were recorded. Compared to respondents who seldom consumed MR products, respondents consuming MR products almost every day were associated with higher cardiac mortality risk (Adjusted HR and 95% confidence intervals: 2.51, 1.07 to 5.91, P value=0.035).

Conclusion:
Habitual consumption of MR products might be associated with higher cardiac mortality risk.
Abstract 12471: Ventricular Tachycardia Ablation vs Antiarrhythmic Drug Efficacy and Safety: A Meta-Analysis and Systematic Review of Randomized Studies
Authors: Habib Muzzamal , Lolait Cian , Boles Usama , Walsh Katie A , Fahy Gerard J , Keelan Edward , Chaudhry G. Muqtada M , Galvin Joseph
Published: June 2023

Introduction:
Ventricular tachycardia (VT) poses a significant risk in patients with ischemic cardiomyopathy. Antiarrhythmic drugs (AAD) and catheter ablation are the 2 strategies employed to reduce the risk of future VT episodes. It is not established if one strategy is superior to the other.

Hypothesis:
Recently, randomized trials have been published comparing the efficacy and safety of both strategies for VT management. Unfortunately, most of these trials included a relatively small number of patients and had different outcomes or composite of outcomes limiting their utility.

Methods:
We performed a meta-analysis of randomized clinical trials comparing these treatment modalities for VT management. Criteria for appropriate studies were the inclusion of outcome data for both ablation and AAD arms, history of documented VT or ICD therapy before enrollments, and use of ICD to reliably monitor the incidence. Due to recent advances in substrate-based VT ablation and changes in ICD algorithms we limited our search for studies published in last 10 years. We identified four studies that met our inclusion and exclusion criteria.

Results:
Our included studies randomized 609 patients, 303 in ablation, and 310 in AAD groups. All-cause mortality data were available for all included studies. The cumulative odds ratio (OR) for all-cause mortality for VT ablation compared to AADs was 0.88, 95% confidence interval [0.56-1.39], p-value 0.58. Cumulative OR for cardiac death was 0.81 [95% CI 0.47-1.38], p-value 0.44, OR for ICD shocks was 0.82[0.57-1.18], p-value 0.29 and the OR for heart failure or cardiac rehospitalization was 0.82 [95% CI 0.53-1.25] p-value 0.35. Treatment-related complications were reported in only two studies with cumulative OR 0.31 [95% CI 0.19-0.51] p <0.00001. Studies used different definitions of treatment related complications.

Conclusions:
VT ablation and antiarrhythmic drugs appear to be equally effective treatment strategies to prevent all-cause death, cardiac death, heart failure rehospitalization, and ICD shocks but there is a trend towards better results for all stated outcomes with ablation. There was statistically significantly lower incidence of the reported treatment-related complications with ablation compared to AADs.
Abstract 12474: Left Atrial Function and Clinical Outcomes After Tricuspid Valve Surgery for Atrial Functional Tricuspid Regurgitation
Authors: Kim Kyu , Ko Kyu-Yong , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Y
Published: June 2023

Background:
Atrial functional tricuspid regurgitation (AF-TR) caused by long-standing persistent atrial fibrillation is a common type of functional tricuspid regurgitation (TR). However, the data of functional changes and prognostic factor for clinical outcome after surgical correction are limited.

Methods:
Among 1,670 patients who underwent tricuspid valve (TV) surgery between January 2000 and December 2020, we included 83 AF-TR patients who had severe TR without any detectable cause other than chronic atrial fibrillation. We analyzed the changes of echocardiographic parameters at baseline, immediate postoperative period, and 6-month from TV surgery. In terms of left atrial (LA) function, LA emptying fraction (LAEF), LA reservoir strain, and LA stiffness index (the ratio of E/e’ and LAEF) were assessed. The primary outcome was composite of all-cause death or heart failure (HF) hospitalization.

Results:
The mean age was 69.1±9.2 years and women (60.2%) were more dominant. Right ventricular (RV) fractional area changes and RV-pulmonary artery coupling index were deteriorated postoperatively, but improved after 6-month. However, the postoperative changes of LAEF, LA reservoir strain, and LA stiffness index were consistent after 6 months from TV surgery. During median follow-up of 39.9 months, the primary outcome occurred in 20 (24.1%) patients. The patients with low baseline LAEF (<16.7%) had significantly higher all-cause death or HF hospitalization incidence (log rank P<0.001). In Cox multivariable regression analysis, LAEF was an independent predictor for primary outcome[p1] [KK2] (adjusted hazard ratio 9.51, 95% confidence interval 2.80-36.3; P<0.001).

Conclusion:
In patients with AF-TR, preoperatively assessed LAEF was an independent predictor of clinical outcome after TV surgery.
Abstract 12476: Dapagliflozin versus Empagliflozin and the Risk for Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Nationwide Population-Based Study
Authors: Lim Jaehyun , Kim Bongseong , Choi You-Jung , Lee Hyun-Jung , Han Kyung-Do , Lee Heesun , Park Jun-bean , Kim Hyung-kwan , Kim Yong-Jin
Published: June 2023

Introduction:
Dapagliflozin and empagliflozin are the two most widely used sodium-glucose co-transporter 2 inhibitors (SGLT2i) for type 2 diabetes (T2DM) worldwide. The study was conducted to compare the cardiovascular outcomes of two SGLT2i, dapagliflozin and empagliflozin.

Methods:
We conducted a nationwide cohort study using the Korean National Health Insurance Service database and an active-comparator new-user design. Patients newly prescribed either dapagliflozin or empagliflozin between 2016 and 2018 for T2DM were retrospectively analyzed and matched in a 1:1 ratio based on propensity scores estimated using 53 potential confounding variables. The primary outcome was major adverse cardiovascular events (MACE), which is a composite of myocardial infarction, ischemic stroke, heart failure (HF) events (i.e., hospitalization for HF or HF-related death), and cardiovascular death. Secondary outcomes were HF events, cardiovascular death, and all-cause mortality.

Results:
A total of 145,502 patients were included in the final analysis (mean age 57±12 years, 57% male). During mean follow-up of 2.1±0.7 years, there was no significant difference in the incidence of MACE between the two groups (incidence rate 6.95 vs. 7.33 per 1000 person-years). The hazard ratio [HR] for dapagliflozin to empagliflozin users was 0.95 (95% confidence interval [CI] 0.87-1.03; P= 0.199). Regarding secondary outcomes, however, compared with empagliflozin users, dapagliflozin users had a lower risk of HF events (HR 0.84, 95% CI 0.71-0.98; P= 0.032), and cardiovascular death (HR 0.82, 95% CI 0.68-1.00; P= 0.047), other than all-cause mortality (HR 1.00, 95% CI 0.92-1.09; P= 0.934).

Conclusions:
In this large nationwide cohort study, the risk of MACE was similar between dapagliflozin and empagliflozin users. Yet, dapagliflozin users, as compared with empagliflozin users, were associated with a reduced risk of hospitalization for HF or HF-related death and cardiovascular death.
Abstract 12486: Impact of New-Onset Persistent Left Bundle Branch Block on Reverse Cardiac Remodeling and Clinical Outcomes After Transcatheter Aortic Valve Replacement
Authors: Kim Kyu , Ko Young-Guk , Shim Chi Y , Ryu JiWung , Lee Yong-Joon , Seo Jiwon , Lee Seung-Jun , Cho Iksung , Hong Sung-jin , Kim Byeong-Keuk , Hong Geu-Ru , Ha Jong-Won , Choi Donghoon , Hong Myeong-Ki
Published: June 2023

Background:
The clinical implication of new-onset left bundle branch block (LBBB) after transcatheter aortic valve replacement (TAVR) remains controversial. We investigated the impact of new-onset persistent LBBB on reverse cardiac remodeling and clinical outcomes after TAVR.

Methods:
Among 478 patients who had undergone TAVR for symptomatic severe aortic stenosis from 2011 to 2021, we analyzed 364 patients after excluding patients with pre-existing intraventricular conduction disturbance or a pacing rhythm before or during the indexed hospitalization for TAVR. Echocardiographic variables of cardiac remodeling at baseline and 1 year after TAVR were comprehensively analyzed. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure. Secondary outcomes were all-cause death and individual components of the primary outcome.

Result:
New-onset persistent LBBB occurred in 41 (11.3%) patients after TAVR. The no LBBB group showed a significant increase in the left ventricular (LV) ejection fraction and decreases in LV dimensions, the left atrial volume index, and LV mass index 1 year after TAVR (all p<0.001). However, the new LBBB group showed no significant changes in these parameters. During a median follow-up of 18.1 months, the new LBBB group experienced a higher incidence of primary outcomes (hazard ratio [HR]: 5.03; 95% confidence interval [CI]: 2.60-9.73; p < 0.001) and all-cause death (HR: 2.80; 95% CI: 1.38-5.69; p = 0.003). The data were similar after multivariable regression analysis.

Conclusion:
New-onset persistent LBBB after TAVR is associated with insufficient reverse cardiac remodeling and increased adverse clinical events.
Abstract 12501: Stronger Positive Correlation Between Left Ventricular Mass Index and E/e' in Patients With Diabetes Compared to Non-Diabetic Subjects
Authors: Miura Hiroyuki , Koseki Masahiro , Ide Seiko , Asaumi Yasuhide , Morita Yoshiaki , Ohta Yasutoshi , Fukuda Tetsuya , Tanaka Katsunao , Okada Takeshi , Omatsu Takashi , Sakata Yasushi , Noguchi Teruo
Published: June 2023

Introduction:
Diabetes mellitus (DM) has been considered as a background of cardiomyopathy. The aim is to characterize the structural and functional features of the heart in diabetic patients by cardiac magnetic resonance imaging (CMR).

Methods:
This was a multicenter, retrospective, observational study: patients aged 45 years or older who underwent contrast-enhanced CMR were included. Patients with low left ventricular ejection fraction (LVEF) (LVEF<40%), known cardiomyopathy, history of myocardial infarction, or type 1 DM were excluded. Left ventricular mass index (LVMi), LVEF, and extracellular volume (ECV), which may represent myocardial fibrosis, were evaluated by CMR. Left atrial pressure was estimated by echocardiographic indices such as E/e’.

Results:
We analyzed 322 patients (age (median [interquartile range]) = 64 [53 - 73], DM (n) = 53). After multivariable adjustment, DM was independently associated with greater LVMi (standard regression coefficient (β) = 0.11, p = 0.037) and lower LVEF (β = -0.12, p = 0.036). In DM patients, LVMi and E/e' were positively correlated (correlation coefficient (R) = 0.46, p = 0.001), with a higher correlation coefficient than those in non-DM patients (R = 0.15, p = 0.022). There was a significant interaction between LVMi and DM for increased E/e' (p = 0.020) (Figure A). ECV also correlated with E/e' only in DM patients (DM, R = 0.55, p = 0.011; non-DM, R = 0.14, p = 0.14), with a significant interaction between ECV and DM for increased E/e' (p = 0.037) (Figure B).

Conclusions:
CMR revealed that diabetic patients without myocardial infarction had increased LVMi with declined LVEF. Both increased LVMi and ECV were also revealed to be associated with higher E/e' especially in diabetic patients.
Abstract 12504: Outcomes of COVID-19 Positive Donor Heart Transplantation in the United States
Authors: Kim Samuel T , Helmers Mark R , Iyengar Amit , Herbst D. Alan , Weingarten Noah , Atluri Pavan
Published: June 2023

Introduction:
Small institutional case series have documented successful heart transplant outcomes using COVID-19 positive (COVID-19+) donor allografts. However, little is known regarding the impact of donor COVID-19 status on a national scale. In this study, we characterize outcomes of the first 84 COVID-19+ donor heart transplants in the United States.

Methods:
Retrospective analysis of the United Network for Organ Sharing database was performed for adult heart transplants from February 2021 to March 2022. Donor COVID-19+ status was defined as a positive nucleic acid amplification, antigen or other COVID-19 test within 7 days of transplant. Fisher’s exact test and Kaplan-Meier survival estimates were used to determine differences in outcomes, including graft failure, post-operative stroke and dialysis, length of stay and 30-day survival.

Results:
Overall, 3,289 heart transplants were included in analysis, with 84 utilizing COVID-19+ donor hearts. COVID-19+ allografts had similar cold ischemic times (3.7 vs 3.5 hours, P=0.22) compared to others. Recipients of COVID-19+ donor organs had similar lengths of stay (15 vs 17 days, P=0.19), rates of graft failure (2.4% vs 1.0%, P=0.22), post-operative stroke (0.0% vs 3.0%, P=0.18), post-operative dialysis (15.5% vs 13.4%, P=0.52) and 30-day post-transplant survival (96.1% vs 97.0%, P=0.63) compared to recipients of non-positive donors. Among the 4 deceased recipients of COVID-19+ allografts, none have died from pulmonary or infectious causes of death. Use of COVID-19+ donors for heart transplantation increased throughout the study period (r=0.79, Figure).

Conclusions:
Short-term outcomes of heart transplant recipients receiving COVID-19+ donor organs are reassuring, providing preliminary evidence that heart transplantation may be safely performed using appropriately selected COVID-19+ donor allografts. Continued monitoring for long-term outcomes and potential complications are warranted.
Abstract 12506: Assessment of the Left Ventricular Trabeculation Phenotype Contributes to Risk Stratification in Hypertrophic Cardiomyopathy Patients
Authors: Zhang Yu , Zhu Yuming , Xu Lianjun , Huang Qiya , Wu Guixin , Wang Jizheng , Zhang Channa , Sun Xiaolu , Jiang Wen , dong wang , Kang Lianming , song lei
Published: June 2023

Aims:
To investigate clinical values associated with the “left ventricular (LV) trabeculation phenotype” that did not meet the diagnostic criteria of LV noncompaction (LVNC) in hypertrophic cardiomyopathy (HCM).

Hypothesis:
The presence of left ventricular trabeculation phenotype was associated with a poor prognosis in HCM patients. Genetic factors contributed to this particular phenotype.

Methods:
A total of 940 HCM patients were recruited. The primary endpoint was cardiovascular death; the secondary endpoints were sudden cardiac death (SCD) and all-cause death. The LV trabeculation phenotype was assessed by cardiac magnetic resonance. Baseline and survival analyses regarding the LV trabeculation phenotype were conducted in general HCM patients and obstructive subset. A combination model was constructed by adding the LV trabeculation phenotype to the HCM risk-SCD model. The whole exome sequencing was used for genetic analysis.

Results:
The LV trabeculation phenotype was recognized in 34.5% HCM patients and was mostly observed at the apex and free wall. Patients with the LV trabeculation phenotype were younger, had a higher prevalence of family history of SCD and more frequent presence of late gadolinium enhancement. Cox proportional hazards regression analysis showed that the LV trabeculation phenotype increased the risk of cardiovascular death (P=0.031), SCD (P=0.008), and all-cause death (P=0.047) in obstructive HCM patients. Furthermore, the LV trabeculation phenotype-combined model improved risk stratification for SCD. The genetic analysis showed that
DTNA
variants were more frequently identified in patients with the LV trabeculation phenotype.

Conclusions:
The LV trabeculation phenotype contributes to risk stratification in obstructive HCM, thus this parameter should be assessed in obstructive HCM patients even if the degree of trabeculation does not fulfil the LVNC criteria.
DTNA
mutation underlies the cause of this phenotype.
Abstract 12520: Pathophysiologic Basis of Angina Symptoms in Women With Nonobstructive Atherosclerosis Using Artificial Intelligence-Enabled Coronary Plaque Analysis
Authors: Tamarappoo Balaji , Flores Tomasino Guadalupe , Calsavara Vinicius , Park Rebekah , Lin Andrew , Handberg Eileen M , Shufelt Chrisandra , Shaw Leslee J , Berman Daniel , Slomka Piotr J , Budoff Matthew , Pepine Carl J , Bairey Merz C. Noel , Dey Damini
Published: June 2023

Background:
Coronary CT angiography (CCTA) artery plaque characteristics including low attenuation and positive remodeling are associated with future myocardial infarction. Associations between angina symptoms and plaque characteristics are unknown.

Objective:
To examine relationships between quantitative plaque characteristics and angina in women with nonobstructive plaque using artificial intelligence (AI)-enabled plaque analysis.

Methods:
A sample of women with angina and CCTA nonobstructive plaque (<50% luminal stenosis) enrolled in the WARRIOR trial (NCT 03417388) was studied with validated AI software (Autoplaque 3.0, Cedars Sinai). Complete coronary plaque composition was expressed as noncalcified (NCP), low attenuation noncalcified plaque (LAP, as NCP<30 Hounsfield Units) and calcified plaque (CP) (Figure). Plaque burden was defined as plaque volume x 100%/vessel volume. Angina was quantified by the Seattle Angina Questionnaire angina frequency domain. Relationships between plaque characteristics and angina frequency at enrollment were evaluated using linear and logistic regression in women with total plaque volume >200mm
3
.

Results:
Among 72 women (age 61.8±10.1 yrs, BMI 30.3±7.2 kg/m2, LDL-C 86.5±27.9, HDL 55.8±17.3, total cholesterol 164.2±37.7 mg/dl, respectively), total plaque volume was 460.1±192.8mm
3
and NCP burden was 50.3± 7.1%. By linear regression, worsening angina frequency was related to increasing NCP burden (β=-0.76, p=0.011). In a logistic regression model, every unit increase in NCP burden was related to ~11% excess risk (1.108, 1.023-1.2, p=0.012) of monthly angina (angina frequency score ≤99).

Conclusion:
In women with nonobstructive coronary plaque and angina in the WARRIOR trial, higher CCTA NCP burden is associated with more frequent angina. Further work with quantitative AI analysis of CCTA from the WARRIOR trial will validate these preliminary findings.
Abstract 12529: Left Ventricular Gene Expression Heterogeneity in a Mouse Model of Dyssynchronous and Resynchronized Heart Failure
Authors: Ljung Karin , Rullman Eric , Pernow John , Nordin Hugo , Vestman Christian , Braunschweig Frieder , Nakagawa Ryo , Kass David A , Stahlberg Marcus
Published: June 2023

Introduction
Cardiac resynchronization therapy improves the prognosis for patients with heart failure and left bundle branch block through cardiac reverse remodeling. The biological mechanisms governing this process remain largely unknown. In a canine model, it has been shown that dyssynchronous heart failure (DHF) induces regional heterogeneity in left ventricular gene expression which is reversed with resynchronization. We developed a mouse model of dyssynchrony and resynchronization and here use this model to test the hypothesis that DHF induces increased intra left ventricular heterogeneity in gene expression that is ameliorated with resynchronized heart failure (RHF).

Methods
Heart failure was induced in mice through ischemia/reperfusion. All mice were implanted with a custom-made pacemaker. In the synchronous HF (SHF) group the pacemaker was turned off. In the DHF group the mice received right ventricular pacing (RVP) for four weeks. In the RHF group mice received RVP for two weeks, after which the pacemaker was turned off for two weeks. Heart tissue from the septum and lateral left ventricular wall was subjected to RNA sequencing.

Results
The expression of 1923 genes differed significantly between early- and late activated left ventricular segments in DHF reflecting regional heterogeneity in gene expression, this disparity was not found in SHF or RHF hearts (Figure A). Figure B shows the ten most significantly upregulated gene ontology (GO) pathways in the lateral wall compared to septum in DHF. These pathways were predominantly associated with cell motility and extracellular matrix processing.

Conclusions
DHF induces a change in gene expression between the left ventricular septum and lateral wall. This difference is absent in SHF and RHF. Our findings support that resynchronization causes a reversal in gene expression from DHF pattern to SHF pattern and may contribute to further understanding of the remodeling process in DHF and how this may be reversed.
Abstract 12531: Electrophysiological Mechanisms of Tachycardia-Induced Cardiomyopathy in Human Myocardium
Authors: Pabel Steffen , Knierim Maria , Stehle Thea , Pöppl Arnold , Hasenfuss Gerd P , Maier Lars S , Streckfuss Boemeke Katrin , Sossalla Samuel
Published: June 2023

Introduction:
Tachycardia-induced cardiomyopathy (TCM) is a reversible form of heart failure. However, the effects of persistent tachycardia leading to TCM in the human are less understood limiting appropriate management of patients with this underrecognized condition. This study investigated the electrophysiological mechanisms of TCM.

Methods and Results:
Tachycardic in vitro electrical stimulation (120 bpm versus 60 bpm control) of human specimen was performed. In human twitching ventricular trabeculae from patients with preexistent heart failure, tachycardia for 8h compromised systolic force, while diastolic tension and relaxation time were increased (n=6/8 patients each). Human iPSC-cardiomyocytes (iPSC-CM) of healthy donors were utilized as human model suitable for extended electrical pacing. After 24h of tachycardia, systolic Ca
2+
-transient amplitude of iPSC-CM was reduced, while diastolic Ca
2+
levels and cytosolic Ca
2+
elimination were not changed (Fura-2, n tachycardia/control=49/44 cells). 7d of tachycardia resulted in a progressive decline of Ca
2+
-transient amplitude together with an impaired Ca
2+
elimination (n=73/66) thereby demonstrating the progression of TCM. Sarcoplasmic reticulum (SR) Ca
2+
load (caffeine application) and SERCA activity (K
sys
-K
caff
) were reduced after 7d of tachycardia (n=13/13). Besides an impaired SERCA activity, we could identify an increased diastolic SR Ca
2+
spark frequency after 7d of tachycardia (n=76/79) as another mechanism of reduced SR Ca
2+
load. In voltage clamp studies, I
CaL
density was reduced after 7d of tachycardia (n=11/12), which may further contribute to impaired systolic Ca
2+
-handling. Conversely, action potential duration was prolonged after 7d of tachycardia compared to control (n=19/21). As a potential explanation for prolonged action potentials however, late sodium current (I
NaL
) was enhanced after 7d of tachycardia (n=26/19).

Conclusions:
This study demonstrates for the first time in human myocardium that persistent tachycardia induces early adverse electrophysiological remodeling that may underlie the progression of TCM. These findings may help to understand the pathophysiology of an underrated but prevalent disease
Abstract 12537: Iron Deficiency in Korean Patients With Heart Failure
Authors: YOON MINJAE , Choi Dong
Published: June 2023

Introduction:
Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF.

Methods:
In this prospective, multicenter cohort study, 461 patients with acute HF seen at five centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin <100 μg/L or ferritin 100-299 μg/L in combination with transferrin saturation <20%.

Results:
The patients’ mean age was 67.6±14.9 years, and 61.8% were male. Overall, 53.8% had ID. In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.18; 91% confidence interval [CI], 1.46-3.26), higher heart rate (OR, 1.01; 95% CI, 1.00-1.02), anemia (OR, 1.80; 95% CI, 1.21-2.67), and the use of clopidogrel (OR, 1.67; 95% CI 1.07-2.06). Among women, the prevalence of ID did not differ between younger and older women (<65 years: 73.7% vs. ≥65 years: 63.0%, P=0.222), those with low and high body mass index (BMI<25 kg/m2: 66.2% vs. BMI≥25 kg/m2: 69.6%, P=0.703), and those with low and high natriuretic peptide (NP) levels (NP <median: 69.8% vs. NP ≥median: 61.1%, P=0.295). Only 0.2% received intravenous iron supplementation.

Conclusions:
The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot solely be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. Efforts should be made to overcome the low use of intravenous iron supplementation in Korea.
Abstract 12541: Development of a Transgenic Rabbit Model of Dravet Syndrome
Authors: Ramos-Mondragon Roberto , Chen Chunling , Ziobro Julie , Chen Yan , Wang Shuyun , Jimenez-Vazquez Eric N , Lopez-Santiago Luis , Parent Jack , Isom Lori L
Published: June 2023

Introduction:
Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. While SUDEP mechanisms are not understood, there is evidence to implicate autonomic dysfunction and cardiac arrhythmias. Loss-of-function variants in SCN1A are linked to Dravet syndrome (DS). Importantly, SCN1A is expressed in both heart and brain in humans and rodents. Studies on Scn1a+/- DS mice and induced pluripotent stem cell (iPSC)-derived cardiac myocytes from DS patients show altered cardiac electrophysiology that serves as substrates for arrhythmias. However, no mouse or iPSC model can completely replicate the human DS phenotype.

Hypothesis:
Cardiac arrhythmias contribute to the mechanisms of SUDEP in a rabbit model of DS.

Methods:
We generate a New Zealand White (NZW) rabbit Scn1a deletion model using CRISPR-Cas9 gene editing. Rabbits were tested using video EEG/ECG telemetry as well as surface ECG under anesthesia. Optical mapping studies were performed in isolated hearts and patch clamp electrophysiology was performed in acutely isolated cardiac myocytes.

Results:
NZW Scn1a-/- kits died by postnatal day (P) 7-9 and showed bradycardia, long QT intervals, and AP prolongation. Cardiac myocytes isolated from NZW Scn1a+/- kits showed increased late sodium current compared to WT. We did not observe behavioral seizures or arrhythmias in NZW Scn1a+/- rabbits, which live normal life spans and breed normally. These data suggested, like mouse models, that the DS rabbit phenotype may be background strain dependent. To test this hypothesis, we crossed Scn1a+/- NZW rabbits to the Dutch Belted (DB) strain. We found that F1:NZW x DB Scn1a+/- rabbits have spontaneous seizures as well as pre- and post-ictal cardiac arrhythmia as assessed by video/EEG/ECG telemetry. Approximately 22% of the kits undergo premature death. Severe seizures are observed in adult animals, but to date no adults have died during seizures.

Conclusions:
F1:NZW x DB Scn1a+/- rabbits model DS in terms of seizures and SUDEP and are an optimal model to investigate neuro-cardiac mechanisms of SUDEP as well as to develop novel therapeutics for DS. To our knowledge, this is the first transgenic large animal model of a developmental and epileptic encephalopathy
Abstract 12545: Adoption of Sacubitril/Valsartan in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The AHA Get With The Guidelines - Heart Failure Registry
Authors: Pierce Jacob B , Li Zhen , Greiner Melissa , LIPPMANN STEVEN , Hardy Natalie C , Shen Xian , Stampehl Mark , Mentz Robert J , Allen Larry A , Peterson Pamela , Fonarow Gregg C , Obrien Emily C , Greene Stephen J
Published: June 2023

Introduction:
In February 2021, the US FDA expanded the indication for sacubitril/valsartan (S/V) to include patients with heart failure (HF) with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF), with benefits most evident among patients with EF below normal. However, the adoption of S/V among patients with EF >40% in US clinical practice is unknown.

Methods:
We identified hospitalizations for HF in the AHA Get With The Guidelines®-Heart Failure registry between January 2016 and December 2021 among patients with EF >40% to 60%, and not receiving dialysis. We evaluated prescription of S/V at discharge, and compared patient characteristics among those prescribed and not prescribed S/V. We also assessed temporal trends in S/V discharge prescription before and after FDA label expansion. We considered prescriptions of S/V on or after March 1, 2021, to have occurred after FDA label expansion.

Results:
Among 151,763 hospitalizations for patients with EF >40-60%, 3,001 (2.0%) included a prescription for S/V at discharge. Patients prescribed S/V were more likely to be younger, male, Black race, and privately insured compared with those not prescribed S/V
(Figure, Panel A).
Those prescribed S/V had lower EF (median 48% [Q1 45%, Q3 55%] versus 55% [50%, 58%]), lower blood pressure, lower rates of kidney disease, and higher rates of ischemic HF and diabetes. Following FDA label expansion, discharge prescription of S/V in the study population more than doubled compared with earlier years (4.3% vs 1.6%; p<0.001), but absolute rates remained low. (
Figure, Panel B
).

Conclusion:
Although the rate of S/V prescription among HF patients with EF >40-60% has significantly increased following FDA label expansion, use of S/V among these patients remains low. Compared with patients not prescribed S/V, patients with EF>40-60% receiving S/V at discharge have a distinct demographic and clinical profile, including tendency for HFmrEF more than HFpEF.
Abstract 12547: Obesity as Risk Factor for Malignant Ventricular Arrhythmias in Phospholamban Cardiomyopathy
Authors: Mahmoud Belend , de Brouwer Remco , van der Heide Myrthe Y , Verstraelen Tom E , Wilde Arthur A , Remme Carol Ann , Kuster Diederik W , Van Der Zwaag Paul A , Sillje Herman H , van den Berg Maarten P , van Veldhuisen Dirk J , Cox Moniek G , Westenbrink B D , De Boer Rudolf A
Published: June 2023

Introduction:
The pathogenic phospholamban (PLN) p.Arg14del mutation can cause severe arrhythmogenic cardiomyopathy. However, disease penetrance and clinical course are heterogenous and can differ largely between affected individuals. The impact of external factors - such as lifestyle - on the clinical course has not been studied yet.

Hypothesis:
We hypothesized that obese PLN mutation carriers have worse clinical outcomes, characterized by a higher burden of malignant ventricular arrhythmias (MVA).

Methods:
PLN p.Arg14del mutation carriers from the Dutch PLN registry with available follow-up (FU) data were included. MVA was defined as either sustained ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter defibrillator intervention or (aborted) cardiac arrest. Patients were categorized into three groups based on their body mass index (BMI): normal weight (BMI 18.5 - 24.9 kg/m
2
), overweight (25.0 - 29.9 kg/m
2
) and obese (BMI
>
30.0 kg/m
2
). Mutation carriers with a BMI < 18.5 kg/m
2
or MVA at baseline were excluded.

Results:
A total of 179 PLN mutation carriers were included in this analysis: 105 (58.7%) normal weight, 59 (33.0%) overweight, 15 (8.4%) obese. The obese group had the highest percentage of MVA (26.7%), followed by the overweight (13.6%) and normal weight (4.8%) groups, as shown in the Kaplan-Meier curve (log-rank 0.016). Continuous BMI was significantly correlated with the incidence of MVA during FU: hazard ratio 1.15 [1.04 - 1.27; p=0.006] per 1-unit increase of BMI, adjusted for age, sex and comorbidities (hypertension, type 2 diabetes mellitus, dyslipidemia, coronary heart disease). Additionally, BMI value predicted MVA with an area under the curve of 0.73 [0.63 - 0.84; p=0.002].

Conclusions:
In PLN p.Arg14del mutation carriers, high BMI values and obesity are associated with higher incidence of MVA. This suggests a potential role for lifestyle intervention in the management of this genetic cardiomyopathy.
Abstract 12563: Creation of an Artificial Intelligence Model For Prediction of Major Adverse Cardiovascular Events Late After Tetralogy of Fallot Repair
Authors: Ishikita Ayako , McIntosh Chris , Lee Myunghyun M , Raptis Stavroula , Liang Tiffany , Hanneman Kate A , Karur Gauri , Roche Susan L , Barron David , Hickey Edward , Wald Rachel M
Published: June 2023

Introduction and Hypothesis:
Despite successful tetralogy of Fallot repair (rTOF) in childhood, advancing age is associated with escalating risk of morbidity and mortality. Published risk scores for prediction of major adverse cardiovascular events (MACE) typically incorporate invasive and/or specialized measures. We hypothesized that an artificial intelligence (AI) model using an array of parameters available in routine clinical practice could successfully predict MACE in rTOF.

Methods:
Adults with rTOF were identified using institutional databases (the prospective observational Comprehensive Outcomes Registry Late After Tetralogy of Fallot Repair [CORRELATE] and the retrospective Toronto Outcomes Registry of Congenital Heart disease [TORCH]). A random forest AI model for prediction of MACE was trained on CORRELATE using repeated random sub-sampling validation. External validation was achieved using non-overlapping retrospective data from TORCH. The MACE composite outcome included all-cause mortality, resuscitated sudden death, sustained ventricular tachycardia (>30 seconds) or heart failure (hospital admission>24 hours).

Results:
In total, 804 subjects were studied and MACE was observed in 73 (9%) subjects. Patients were either included in the training dataset (n=312, 59% male, median age 32 years [IQR 23-43], median follow-up 6 years [IQR 4-7]) or the testing dataset (n=492, 58% male, median age 26 years [IQR 20-37], median follow up 10 years [IQR 6-10]). Variables incorporated into the AI model are shown (Figure 1). Predictive capacity of the AI models were similar in testing (AUC 0.81, CI 0.75-0.86) and training (AUC 0.88, CI 0.71-0.99) datasets with excellent receiver operating characteristics (Figure 1).

Conclusions:
An AI model based on routinely used and widely available clinical and imaging variables could successfully predict MACE in rTOF. Further study is required to determine the value of AI for risk management in rTOF.
Abstract 12566: Use Of Aortic Valve Area Index By Actual Body Weight Overestimates Aortic Stenosis Severity In Obese Patients
Authors: Deng Lixia , Lu Mengyun , Bao Chen , Downey Brian C , Wessler Benjamin S
Published: June 2023

Introduction:
Guidelines recommend indexing aortic valve area (AVA) to body surface area in grading the severity of aortic stenosis (AS), which overestimates severity in obese patients. The indexing of AVA to ideal or adjusted body weight has not been explored.

Hypothesis:
We hypothesized that using actual body weight compared to ideal or adjusted body weight in obese patients would result in overestimation of the severity of AS using AVAi.

Methods:
We conducted retrospective chart review on 305 individuals who received a transthoracic echocardiogram (TTE) at Tufts Medical Center from June 2021 to Sept. 2021 with AVA <1.5cm
2
. We selected 73 subjects with moderate AS (AVA 1-1.5cm
2
). These subjects were divided into an overweight and obese group (BMI > 25; n = 56) and a normal weight group (BMI 18-24.9; n = 17). We recorded baseline characteristics and TTE data. AVAi was calculated with actual, ideal, and adjusted body weight. The primary outcome was reclassification, defined as a change in severity from severe AS to mild or moderate AS after recalculating AVAi using adjusted or ideal body weight.

Results:
The overweight and obese group was significantly younger (age 74.4±11.2 versus 80.7±5.7 years, P=0.018) with higher BSA (2.0±0.2 versus 1.7±0.2, P=0.010) compared to the normal weight group. The recorded median AVAi was 0.61 with interquartile range(IQR) of 0.17. There was no significant difference in blood pressure, ejection fraction, AVA, peak aortic velocity, peak gradient, and mean gradient. After calculating AVAi with adjusted and ideal body weight, 18 patients in the overweight and obese group were reclassified to a lower grade of AS based on AVAi (median AVAi 0.58, IQR 0.17), compared with 0 reclassifications in the normal weight group (0.67, 0.18). Patients who were reclassified had a significantly smaller AVA compared to patients who were not reclassified (1.09±0.11 versus 1.23±0.19 cm
2
, P<0.001), while no differences were observed in peak gradient, mean gradient, and peak velocity.

Conclusions:
Using actual body weight to calculate AVAi in overweight and obese patients can lead to overestimation of AS severity. Further research is needed to investigate the optimal indexing strategy for AVAi and the effects of classification on cardiovascular outcomes.