bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12571: Optimal Rate Control Strategy in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Trials and Multivariable Adjusted Studies
Authors: Abi-Kair Borges Calomeni Pedro , CARVALHO LIS VICTORIA RAVANI , de Miranda Gauza Mateus , Pereira Jussara , Cardoso Rhanderson
Published: June 2023

Introduction:
Atrial fibrillation (AF) is associated with an increased risk of impaired quality of life, stroke, and mortality. Despite multiple studies, the optimal target for rate control in AF is not definitively known.

Methods:
We performed a systematic review and meta-analysis comparing the effects of strict rate control (<80 bpm at rest) with a lenient rate control strategy (<110 bpm at rest) in patients with AF. The outcomes analyzed were all-cause mortality, cardiovascular (CV) death and CV hospitalization. A subgroup analysis was also performed in patients with heart failure (HF). PubMed, Scopus and Cochrane Central were searched for randomized controlled trials or observational studies with multivariable analyses adjusting for confounders.

Results:
Seven studies were included. All studies were either randomized or reported multivariate adjusted hazard ratios. There were 14,154 (59.6%) patients in the strict rate control strategy and 9,606 (40.4%) in the lenient group. AF was reported as paroxysmal in 1,697 (7.3%) patients. All-cause mortality was not statistically different between a strict vs. lenient heart rate control strategy, although there was a tendency towards improvement in the strict control group (HR 1.10; 95% CI 1.00-1.22; p=0.05; Figure 1A). In patients with AF and HF, there was also no significant difference between groups (HR 1.13; 95% CI 0.99-1.30; p=0.08; Figure 1B). Furthermore, CV death (HR 0.91; 95% CI 0.75-1.11) and CV hospitalization (HR 1.01; 95% CI 0.96-1.06) were also not significantly different between the two strategies.

Conclusions:
There was no significant difference in all-cause mortality between strict and leninent rate control in patients with AF among randomized trials or multivariable adjusted studies. In a subgroup of patients with HF, there was also no significant difference between the two rate control strategies.
Abstract 12581: The N
6
-Methyladenosine Methylase Wtap is Essential for Cardiac Homeostasis
Authors: Han Ziqiang , Zou Yubao , Li Shuai , Lu Minjie , Nie Yu , song lei , Wang Jizheng
Published: June 2023

Introduction:
N
6
-methyladenosine (m
6
A) methylation is one of the most common internal modifications in mammalian mRNA, and WTAP is a critical regulatory subunit of the RNA N
6
-methyladenosine methyltransferase complex. However, the roles of WTAP in cardiac structure and function are rarely known.

Methods and Results:
We found that the levels of m
6
A RNA methylation and the expression of WTAP were both decreased in myocardial tissue of the patients with hypertrophic cardiomyopathy, as well as in pressure overload-induced cardiac hypertrophy in mice. To determine the regulatory roles of WTAP, a conditional cardiac-specific knockout mice of WTAP was generated through Tamoxifen-inducible αMHC-Cre/loxP system. Depletion of WTPA resulted in heart failure in five days after Tamoxifen treatment, shown by enlarged heart and decreased left ventricular ejection fraction. Furthermore, we found WTAP knockout aggravated the progress of pathogenic cardiac remodeling induced by pressure overload, and abrogated the compensated response cardiac hypertrophy to hypertrophic stimulation. We found MYLK4 was a direct target of WTAP through a methylated RNA immunoprecipitation (MeRIP) sequencing, and it was validated by MeRIP-qPCR, RT-qPCR and RIP-qPCR. RNA stability analysis and dual-luciferase assays showed that depression of WTAP decreased m6A level of MYLK4 mRNA and resulted in a down-regulation of MYLK4 by reducing its RNA-stability. Forced overexpression of MYLK4 adeno-associated virus was able to partly alleviate the cardiac dysfunction induced by WTAP deletion. Finally, it was surprising that overexpression of WTAP also promotes pathogenic cardiomyocyte hypertrophy both in vitro and in vivo, as well as exacerbated cardiac remolding induced by pressure overload.

Conclusions:
In conclusion, our study demonstrates that WTAP is a critical regulator of cardiac function and indicates that appropriate m
6
A RNA methylation is required for cardiac homeostasis.
Abstract 12598: Effect of Mavacamten on Systolic Anterior Motion of the Mitral Valve and Mitral Regurgitation in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From the VALOR-HCM Study
Authors: Cremer Paul C , Geske Jeffrey B , Owens Anjali T , Jaber Wael A , Harb Serge C , Saberi Sara , Wang Andrew , Naidu Srihari S , Schaff Hartzell V , Smedira Nicholas G , Wang Quing , Lampl Kathy , Sehnert Amy J , Nissen Steven E , Desai Milind Y
Published: June 2023

Introduction:
In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. The current sub-study sought to assess the impact of mavacamten on systolic anterior motion (SAM) of the mitral valve and associated mitral regurgitation (MR).

Methods:
Patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. SAM was assessed as none, mild (anterior leaflet >/= 1 cm from the septum), moderate (anterior leaflets <1cm from the septum), and severe (anterior leaflet in contact with septum). MR was assessed according to ASE guidelines.

Results:
Among 112 enrolled patients, 23.2% (n=27) had at least moderate (2+) MR. Most (92.9%, n=104) had at least moderate resting SAM, of whom 55.4% (n = 62) had severe SAM. At 16 weeks, 53.7% of patients treated with mavacamten had at least one level improvement in resting SAM compared to 21.6% of patients treated with placebo (
p
= 0.001), and 35.2% had at least a two level improvement in SAM compared with 11.8% of placebo patients (
p
= 0.007)(Figure 1A). Similarly, patients treated with mavacamten had an improvement of -36.0
+
28.8 mmHg in resting left ventricular outflow tract gradient at week 16 compared to -1.5
+
26.5 mmHg with placebo (<0.001). At week 16, 48.1% of patients treated with mavacamten had at least a one grade improvement in MR, and 23.1% had at least a two grade improvement compared to 12.2% and 6.1% of patients treated with placebo (
p
<0.001 and 0.025, respectively)(Figure 1B).

Conclusions:
In highly symptomatic patients with oHCM, treatment with mavacamten reduced resting SAM with an improvement in associated MR.
Abstract 12600: Mitral Annular Disjunction: How Accurate Are We? A Cardiovascular MRI Study Defining Risk
Authors: Hussain Nasir , Bhagia Geeta , Doyle Mark , WILLIAMS RONALD B , Rayarao Geetha , Biederman Robert W
Published: June 2023

Background:
Mitral Annular Disjunction (MAD) refers to embryologic fibrous separation between mitral annular ring and basal left ventricular myocardium. Since its original description, the role of MAD in arrhythmic mitral valve prolapse (MVP) has been subject of active research. In this study we sought to assess prognostic and imaging characteristics of MVP patients with and without underlying MAD.

Methods:
Patients with posterior or bi-leaflet MVP were retrospectively identified via a review of all patients referred to our cardiac magnetic resonance (CMR) imaging laboratory from January 2015 to May 2022. MVP patients were further stratified by underlying MAD status. CMR characteristics including late gadolinium enhancement (LGE) distribution, clinical characteristics, and data on mitral valve intervention were determined.

Results:
A total of 100 MVP patients undergoing CMR imaging (52 MVP patients with posterior MAD) were retrospectively identified with female comprising 55% of the cohort. MVP patients with MAD were more likely to have an abnormal basal inferolateral/ papillary muscles LGE (51% vs 21%, p<0.01). Posterior MAD longitudinal disjunction gap in ‘mm’ was a predictor of ventricular tachycardia (VT) [1.23, p=0.03)]. Similarly, posterior MAD as a binary variable was predictor of VT (11, p<0.01), ventricular arrhythmia (composite of VT, and non-sustained VT) (2.4, p=0.03), and major adverse cardiac events (MACE) (composite of VT, syncope, and mitral valve intervention) (2.5, p=0.03). Using ROC curve analysis, a disjunction gap of
>
4 mm was predictive of VT (AUC-0.71, p<0.01), and incorporation of LGE in ROC model further improved AUC to 0.78 confirmed via Akaike information criterion (p<0.05), see Figure.

Conclusion:
Abnormal LGE involving basal inferolateral myocardium and papillary muscles may provide substrate for arrythmia in MVP patients. Further, for the first time, a MAD threshold of
>
4 mm is demonstrated to stratify the VT risk.
Abstract 12604: Coronary Artery Calcium Score Determined From Pre-Ablation Pulmonary Vein Computed Tomography Allows for Diagnosis of Coronary Artery Disease and Improved Atherosclerotic Cardiovascular Disease Risk Prediction
Authors: Nmai Christopher , Manmadhan Arun , Sharma Gaurav , Heffron Sean P
Published: June 2023

Objective:
Coronary artery calcification (CAC) is a useful adjunct for atherosclerotic cardiovascular disease (ASCVD) risk stratification and can influence preventive strategies. However, CAC screening is infrequently done, even among cardiology patients. Ancillary imaging, for example pulmonary vein CT (CTPV) performed prior to atrial arrhythmia ablation, may allow for CAC quantification. Our goal was to assess CAC prevalence on pre-ablation CTPVs and to assess how this information could influence risk stratification.

Methods:
Patients undergoing atrial arrhythmia ablation at NYU from 4/1/18 to 4/30/19 were identified and all available medical records reviewed. CTPVs were reviewed and CAC graded semi-quantitatively (0, 1-9, 10-99, 100-399, 400-999, 1000+). 10-yr ASCVD and MESA scores were calculated for patients without known ASCVD.

Results:
739 patients underwent ablations and 660 had CTPV available for assessment. Mean age was 63.4 ± 11.4 years, 33.9% were female, and 17.1% had a history of ASCVD (prior MI, CVA/TIA, CAD, PAD). CAC was present in 62% of patients, including 57.2% without ASCVD history (22.3% of these had CAC ≥100). Complete data for the calculation of 10-year AHA/ACC and MESA risk scores were present in 27.9% and 32.4%, respectively. MESA CHD risk score allows for the incorporation of CAC for improved predictive capacity. Median MESA risk was 6.5% without and 6.7% with median CAC included. Incorporating CAC into MESA risk decreased risk in 110 patients (79 of these had CAC <10), and increased risk in 102 patients (101 had CAC ≥10) (
Figure
). AHA/ACC ASCVD risk distribution is displayed in
Figure.
Guidelines recommend consideration of statins in those with ASCVD risk <7.5% and non-zero CAC. 52.4% of patients with ASCVD risk <7.5 had non-zero CAC (
Figure
) with 18.2% on a statin at the time of their procedure.

Conclusion:
Quantification of CAC on CTPV can provide a means to diagnose CAD, improve risk stratification and impact primary preventive treatment.
Abstract 12605: Sex Differences in Cardiovascular Revascularization Strategies and Outcomes in Dialysis Patients
Authors: Shah Silvi , Christianson Annette , Meganathan Karthikeyan , Leonard Anthony , thakar charuhas
Published: June 2023

Background:
Coronary artery disease is the leading cause of mortality in patients with kidney failure. Little is known about sex differences in revascularization strategies and the associated risk of death in dialysis patients.

Methods:
We evaluated 60,492 patients who initiated dialysis between 1/1/2005 and 12/31/2018 and had at least one hospitalization with a primary diagnosis of an acute coronary syndrome (ACS), using the United States Renal Data System with linked Medicare claims, we examined the association of sex with initial cardiac revascularization (defined as coronary artery bypass graft [CABG], percutaneous coronary intervention [PCI], or both on the same day) within 30 days of the first ACS hospitalization using adjusted multinomial regression, and the association of sex and initial cardiac revascularization on the outcomes of all-cause death and myocardial infarction using adjusted time-to-event models.

Results:
The mean age of patients at index ACS hospitalization was 72±11 years, and 40.4% were women. Overall, 40.5% received PCI, 20.8% received CABG, and 6.1% received both CABG and PCI. After an index ACS event, as compared to no revascularization, women as compared to men had a 41% lower likelihood of receiving CABG (OR, 0.59; 95% CI, 0.56-0.62), 13% lower likelihood of receiving PCI (OR, 1.48; 95% CI, 1.42-1.55), and 41% lower likelihood of receiving CABG and PCI (OR, 0.59; 95% CI, 0.55-0.64). Women had a slightly lower risk of all-cause death during the follow-up period than men without treatment (HR, 0.87; 95% CI, 0.85-0.90) or after receiving PCI (HR, 0.94; 95% CI, 0.90-0.97), but no difference in all-cause death after receiving CABG, and after receiving both CABG and PCI. Women had a higher risk of having MI after receiving CABG (HR, 1.12; 95% CI, 1.05-1.19), and a lower risk of MI after receiving PCI.

Conclusion:
Among patients undergoing dialysis with ACS, women receive less treatment with CABG or PCI than men. Women have a lower adjusted risk of all-cause mortality with PCI, a lower risk of MI after PCI, and a higher adjusted risk of MI with CABG, as compared to men. Revascularization strategies for CV disease may need to be modified based on sex.
Abstract 12608: Design and Fabrication of a Working Tissue Model of the Developing Embryonic Heart
Authors: Gershlak Joshua R , Miki Kenji , Ott Harald
Published: June 2023

Introduction:
Currently, there are no
in vitro
models that fully recapitulate cardiogenesis. Knowledge gained by a three-dimensional model of cardiogenesis could be useful to improve techniques to engineer heart tissue or to act as a model of the onset of congenital heart defects. Within this study, we designed a tissue engineered model of the embryonic heart tube that undergoes the looping phenomenon.

Methods:
Embryonic heart tubes (EHT) were engineered using a novel casting method (Figure 1A, B). Tubes were created through serial castings resulting in an inner acellular layer surrounded by a thin iPS derived cardiomyocyte layer, mimicking the
in vivo
cross-sectional anatomy. In the developing heart, looping is driven through both internal and external forces, leading to elongation of the tube resulting in a rightward rotation at the cranial end of the embryo and a dorsal deflection at the caudal end. To mimic this, we designed a bioreactor system (Figure 1C) that would enable 180°rotation on the “cranial end”, 300% dorsal deflection on the “caudal end”, shortening by 100% for the entire tissue.

Results:
EHTs were maintained for seven days via perfusion culture (Figure 1D). Histologic analysis confirmed cross-sectional orientation that matches the native heart tube at day 22 (Figure 1B). EHTs were found to remain patency, perfusability and viability during culture (Figure 1E). When exposed to external forces within the bioreactor, tubes looped similarly to what is seen during cardiogenesis with both ends fusing together into a primitive four-chambered shape (Figure 1D, F; numbers indicate location within the tissue the image was taken), including potential ventricular septal formation (white arrow).

Conclusions:
We successfully engineered a heart tube model that mimics the cross-sectional anatomy and looping of the embryonic heart tube. This model could be further expanded to further study cardiogenesis or modified to study the onset of congenital heart defects.
Abstract 12620: Effects of Financial Status on Engagement in Self-care in Rural Caregivers With Cardiovascular Risk Factors
Authors: Chung Misook L , Miller Jennifer , Lennie Terry A , Feltner Frances J , Moser Debra K
Published: June 2023

Introduction:
Caring for adults with chronic illnesses increases the risk of developing cardiovascular disease (CVD). Engaging in self-care of healthy behaviors is critical for caregivers, but it may be more difficult due to financial hardship and psychological distress among those living in socioeconomically distressed rural areas. The study's purpose was to examine the association of financial status with engagement in self-care and whether this association is mediated by depressive symptoms in rural caregivers.

Methods:
We used baseline data from 300 rural caregivers (mean age 55 years, 76% female) with at least 2 CVD risk factors participating in a CVD risk reduction intervention trial. They provided data on financial status (3 groups: more than enough, enough, and not enough to make ends meet), depressive symptoms (Patient Health Questionnaire), self-care engagement (MOS-Specific Adherence Scale), caregiving time/difficulty (Oberst Caregiving Burden Scale), and physical assessments for estimating Framingham CVD risk score. Mediation analysis with a multi-categorical antecedent was conducted controlling Framingham risk score and caregiving time/difficulty.

Results:
Those with more than enough (27%), enough (56%), and not enough (56%) to make ends meet had similar Framingham risk scores (M = 12.3, P = .61). Compared to the more than enough group (Figure 1), the not enough group had lower self-care engagement scores (direct effect = -6.48) that were reduced further by the influence of depressive symptoms (indirect effect = -1.19). The results were similar for the enough to make ends meet group (direct effect= - 2.67; indirect effect = -.70).

Conclusion:
Poor financial status was directly associated with decreased engagement in self-care and indirectly associated through increased depressive symptoms. Promoting self-care strategies should include managing depressive symptoms for rural caregivers with a high risk of CVD who report financial hardship.
Abstract 12623: Association Between Past and Present Operative Mortality in Congenital Heart Surgery
Authors: Pasquali Sara K , O'Brien Sean M , Shahian David M , Romano Jennifer , Jacobs Jeffrey P , Mayer John E
Published: June 2023

Introduction:
Operative mortality following congenital heart surgery is a foundational metric used across a variety of benchmarking, quality improvement, and public reporting initiatives. All of these efforts rely on mortality estimates reported from prior years, and it is unclear how well these reflect current outcomes.

Methods:
Adjusted operative mortality among Society of Thoracic Surgeons Congenital Heart Surgery Database index operations (2014-2019) was analyzed using standard risk-models. The association of mortality in “past” 4- and 1-year time intervals vs. the most recent year in the dataset (“present”) was evaluated using Bayesian hierarchical logistic regression. Estimates and 95% credible intervals (CrI) are presented.

Results:
Among 115,699 operations (106 hospitals) present observed mortality ranged from 2.3%-3.1% across quartiles, with regression to the mean evident more so vs. past 1-year than past 4-year data. Odds of present mortality were 2.04 (95%CrI 1.44-2.80) times higher for those in the past worst vs. best 4-year mortality quartile; no significant association was observed for the middle quartiles. The proportion of present hospital mortality variation explained by past mortality quartile was 52% (95%CrI 20%-90%) using past 4-year and 27% (95%CrI 2%-83%) using past 1-year data. Overall 66% of hospitals changed mortality quartiles from past to present (30% by 2 or more quartiles), with lower volume hospitals most impacted.

Conclusions:
Past mortality relates to present mortality primarily for groups of hospitals at the extremes, with past 4-year more informative than past 1-year data. However when considering individual hospitals, past may differ from present, regression to the mean is common, and many hospitals change quartiles. Past mortality estimates should be used thoughtfully and not as the sole factor informing present decision making.
Abstract 12631: Phenome-Wide Prediction of Incident Circulatory Diseases Using Machine Learning-Derived Features From Retinal Imaging
Authors: Zekavat Seyedeh , Doroodgar Saman , Raghu Vineet , Sekimitsu Sayuri , Rossin Elizabeth , Wiggs Janey , Batra Puneet , Ghassemi Marzyeh , Zebardast Nazlee , Natarajan Pradeep
Published: June 2023

Purpose:
The retina is a window for assessment of cardiovascular health. Here, we performed machine learning-based assessment of retinal vascular density (RVD) from fundus photos, and combined this with retinal layer thicknesses from optical coherence tomography (OCT) imaging, to predict incident circulatory conditions.

Methods:
We utilized UK Biobank participant retinal fundus images (N=54,813), and OCT images (N=44,823). Deep-learning of fundus photos was used to remove poor-quality images and segment the retinal microvasculature to calculate RVD. Using the Topcon Segmentation algorithm, we quantified retinal layer thicknesses. We performed Cox survival analyses, separately associating RVD and retinal layer thicknesses with 130 circulatory conditions from Phecode ICD-9 and ICD-10 composite phenotypes (median 10 year follow-up), adjusting for age, sex, smoking, ethnicity, height, weight, and spherical equivalent. False Discovery Rate (FDR<0.05) correction was performed to identify significant associations.

Results:
Participants’ mean age was 56 (SD 8 years), 55% were female, and 56% were non-smokers. Associations were observed for each SD of photoreceptor thinning with incident abdominal aortic aneurysms (HR 1.47, P=6e-6), peripheral vascular disease (HR 1.32, P=4e-5), nonhypertensive heart failure (HR 1.20, P=2.8e-6), myocardial infarction (HR 1.17, P=8e-7), cerebrovascular disease (HR 1.15, P=1.9e-5) and hypertension (HTN) (HR 1.09, P=1e-12). Each SD of lower RVD was associated with incident HTN (HR 1.15, P=3.8e-39) and hypertensive heart disease (HR 2.07, P=6e-4). Further incident heart failure analysis additionally adjusting for RVD, prevalent HTN, and type 2 diabetes identified a persistent association for photoreceptor thinning.

Conclusions:
Our results indicate that photoreceptor thinning and RVD from retinal imaging can serve as a biomarker for future cardiovascular conditions, independent of other common risk factors.
Abstract 12634: A Novel
in-vitro
Patient-Specific Re-Engineered Cardiomyocyte Model of Multifocal Ectopic Purkinje-Related Premature Contractions
Authors: Gao Xiaozhi , Ye Dan , Zhou Wei , Hamrick Samantha K , Kim Changsung , Tester David J , Giudicessi John , Ackerman Michael J
Published: June 2023

Introduction:
Multifocal ectopic Purkinje-related premature contractions (MEPPC), the most recent addition to the spectrum of
SCN5A
-mediated cardiac channelopathies, is characterized by frequent premature ventricular complexes (PVCs) originating from the Purkinje system, atrial arrhythmias, and a predilection for PVC-mediated dilated cardiomyopathy.

Hypothesis:
To investigate the electrophysiology phenotype of MEPPC in a novel, patient-specific, re-engineered cardiomyocyte model.

Methods:
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a 27-year-old male with a history of frequent, multifocal PVCs and atrial tachycardia, positive for a putative MEPPC-causative
SCN5A
variant (p.Q419P). A CRISPR-Cas9 Q419P variant-corrected isogenic control (IC) was created to establish the normalized electrophysiology recordings for that MEPPC model. The standard whole-cell patch clamp technique was used to measure Q419P-SCN5A- and IC-derived NaV1.5 sodium currents using voltage clamp configuration. In addition, action potential duration (APD) of the iPSC-CMs were measured using FluoVolt optical voltage-sensing dye.

Results:
Analysis of the current-voltage relationship revealed that neither peak sodium current densities nor late inward sodium current were impacted by Q419P-SCN5A. However, Q419P-SCN5A significantly right-shifted the V
1/2
in inactivation by 8.3 mV from -81.1±1.7 mV (IC, n=5) to -72.8±0.2 mV (Q419P-SCN5A, n=6, p<0.05 vs. IC) and left-shifted the V
1/2
in activation by -4.1 mV from -39.5±0.3 mV (IC, n=5) to -43.6±0.9 mV (Q419P-SCN5A, n=6, p<0.05 vs. IC) leading to a larger hyperpolarized window current. Optical APD90 measurement revealed no difference between the Q419P-containing (476 ± 23 ms) and the IC (474 ± 46 ms, p=0.867) cardiomyocytes.

Conclusions:
This is the first
in-vitro
disease model of MEPPC using patient-specific, re-engineered heart cells. Consistent with the findings in the non-cardiac HEK cell system, this MEPPC-causative variant contributes to increased window current in cardiomyocytes without affecting the cardiac APD. This novel cardiac cell model for MEPPC may facilitate new insights into the pathobiology of MEPPC and enable the testing of novel therapies for it.
Abstract 12635: Mortality Risks and Need For Transplant in Pediatric Heart Disease Associated With Lower Ses and Greater Remoteness of Residence From Cardiac Care
Authors: Conway Jennifer , Smith Christopher , Dover Douglas C , Mackie Andrew , Mackie Andrew S , Kaul Padma , Hornberger Lisa K
Published: June 2023

Introduction:
Socioeconomic status (SES) and remoteness of residence (RoR) may contribute to worse clinical outcomes. Whether this is true in universal healthcare is not certain. We sought to explore associations between SES and RoR, from centralized pediatric cardiac care, and a composite of mortality and need for transplant (Tx) in children with congenital (CHD) and acquired heart disease (AHD).

Methods:
All infants born in Alberta, Canada between 01/01/05 and 31/12/17, and diagnosed before 31/12/17 were included. CHD was categorized as mild, moderate or severe based on the Bethesda Task Force. AHD included cardiomyopathy, myocarditis, heart failure, rheumatic heart disease and endocarditis. Socioeconomic status (SES) was defined by the Canadian Index of Multiple Depravation’s vulnerability index and RoR was calculated using the drive time to one of two pediatric cardiology centers. Risk factors for a composite of mortality and Tx were explored using Cox proportional hazard regression.

Results:
Among 12,542 children, 74.5% (n=9347) had mild CHD, 13.8% (n=1733) moderate, 5.7% (n=717), severe and 5.9% (n=745) AHD. The composite outcome was highest in severe CHD (19.0%), compared to 13.0% in moderate, 0.5% for mild and 6.9% in AHD, with n=41 undergoing Tx. Among children with CHD, RoR (>180mins, p=0.018), but not SES, was associated with all-cause mortality/Tx (Table 1), while neither RoR (p=0.73) nor SES (p=0.98) were associated with cardiovascular (CV)-specific mortality/Tx. For AHD there was no association between RoR (p=0.73) and SES (p=0.98) with all-cause mortality/Tx (Table 1).

Conclusions:
Despite Canada’s universal healthcare, children with CHD who live remotely are at increased risk of all-cause mortality/Tx. This is independent of SES and was not true for children with AHD or CV mortality/Tx in those with CHD. Therefore, further understanding of the causes of death in children who live remotely with CHD may help in improving overall outcomes.
Abstract 12636: Association Between Pre-Operative Specialist Assessment and Adverse Outcomes Among Patients Scheduled for Major Vascular Surgery
Authors: de Mestral Charles , Abdel Qadir Husam M , Austin Peter C , Chong Alice , Finlay McAlister A , Lindsay Thomas F , Ross Heather , OREOPOULOS GEORGE , Wijeysundera Duminda N , Lee Douglas S
Published: June 2023

Background:
The impact of pre-operative specialist assessment on outcomes following high-risk vascular surgery remains uncertain. Our objective was to characterize the association between pre-operative cardiology or general internal medicine (GIM) assessment and post-operative outcomes following scheduled major vascular surgery.

Methods:
This is a population-based cohort study of all adult scheduled major vascular surgery patients in Ontario, Canada (April 1, 2004-March 31, 2019). Those who underwent an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Multivariable cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication.

Results:
Among 50,228 scheduled major vascular surgery patients, 20,484 underwent pre-operative ambulatory specialist assessment: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Patients who underwent cardiology or GIM assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989 [24.4%] vs. 4,587 [15.4%], p<0.001) and more frequent pre-operative cardiac testing (N=7,772 [37.9%] vs. 6,113 [20.6%], p<0.001) but had lower crude 30-day mortality (N=551 [2.7%] vs. 970 [3.3%], p<0.001). After application of IPTW, pre-operative specialist assessment remained associated with a lower rate of 30-day mortality (Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes (Figure).

Conclusion:
Pre-operative ambulatory cardiology or GIM assessment is associated with improved outcomes following scheduled major vascular surgery
Abstract 12646: Health Status Outcomes in Older Adults Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Nguyen Dan D , Gosch Kensey , El-Zein Rayan , Chan Paul S , Lombardi William L , Karmpaliotis Dimitrios , Spertus John A , Wyman Cathi M , Nicholson William , Moses Jeffrey W , Grantham J. Aaron , Salisbury Adam C
Published: June 2023

Background:
Although CTOs are common in older adults, they are less likely to be offered CTO percutaneous coronary intervention (PCI) for angina relief than younger adults. The health status impact of CTO PCI in adults ≥75 years old has not been studied. We sought to compare technical success rates and angina-related health status outcomes at 12-months between adults ≥75 and <75 years old in the OPEN-CTO registry (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Registry).

Methods:
Angina-related health status was assessed with the Seattle Angina Questionnaire (SAQ; score range 0-100, higher scores denote less angina). Technical success rates were compared using hierarchical modified Poisson regression, and 12-month health status was compared using hierarchical multivariable linear regression between adults ≥75 and <75 years old.

Results:
Of the 1000 patients enrolled, 19.8% were ≥75 years old with a mean age of 79.5 ± 4.1 years. Age ≥75 years was associated with a lower likelihood of technical success (adjusted RR = 0.92, 95% CI 0.86, 0.99, p=0.02) and numerically higher rates of in-hospital major adverse cardiovascular events (9.1% vs 5.9%, p=0.10). There was no difference in SAQ Summary Score at 12-months between adults ≥75 and <75 years old (adjusted difference 0.9, 95% CI -1.4, 3.1, p=0.44) (Figure).

Conclusions:
Despite modestly lower success rates and higher complication rates, adults ≥75 years old experienced angina-related health status benefits after CTO-PCI that were similar in magnitude to adults <75 years old. CTO PCI should not be withheld based on age alone in otherwise appropriate candidates.
Abstract 12648: Comparison of Transthyretin Amyloid Cardiomyopathy Patients Taking Tafamidis and Those Not Taking Tafamidis Using Two-Dimensional Speckle Tracking Echocardiography
Authors: Oike Fumi , Usuku Hiroki , Egashira Kouichi , Komorita Takashi , Fujisue Koichiro , Sueta Daisuke , Takashio Seiji , Yamamoto Eiichiro , Tsujita Kenichi
Published: June 2023

Objectives:
Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study investigated the effect of tafamidis on left heart function in ATTR-CM patients by using two-dimensional speckle tracking echocardiography.

Methods and Results:
We evaluated 222 consecutive patients with ATTR-CM who were diagnosed at our department between January 2002 and February 2022 retrospectively. Eighty patients taking tafamidis had a history of echocardiography before and 12 months after treatment, and thirty-four untreated patients had a history of echocardiography after diagnosis and 12 months later. Serum high-sensitivity cardiac troponin T (hs-cTnT) significantly decreased in the treatment group (hs-cTnT :0.067±0.037 vs. 0.056±0.031, p<0.01) but didn’t change significantly in the untreated group (hs-cTnT :0.085±0.110 vs. 0.084±0.070, p=0.98). Plasma B-type natriuretic peptide did not change significantly in each group. Creatinine increased significantly in the treatment group (creatinine:1.12±0.31 vs. 1.19±0.50, p=0.03) and did not change in the untreated group (creatinine:1.40±0.91 vs. 1.48±0.90, p=0.17). Left ventricular global longitudinal strain (LVGLS) and left atrial strain rate during atrial contraction (LASRa) didn’t change significantly in the treatment group (LVGLS: -8.4±2.9 vs. -8.3±2.9, p=0.30 LASRa: -0.24±0.21 vs. -0.23±0.18, p=0.49) but increased significantly in the untreated group (LVGLS: -10.9±3.3 vs. -7.8±5.2, p<0.01, LASRa: -0.44±0.39 vs. -0.29±0.24, p=0.01).

Conclusion:
Tafamidis may be effective in maintaining left heart function in ATTR-CM patients.
Abstract 12656: Is the Benefit of Posterior Wall Isolation in Conjunction With Pulmonary Vein Isolation the Same for Patients With Paroxysmal vs. Persistent Atrial Fibrillation - A Meta-Analysis
Authors: Milstein Nicolle S , Musat Dan L , Bhatt Advay G , Habibi Mohammadali , Sichrovsky Tina C , Preminger Mark W , Shaw Richard E , Mittal Suneet
Published: June 2023

Introduction:
Pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation procedures. Because many patients have continued AF after PVI alone, posterior wall isolation (PWI) has been proposed as an adjunctive strategy to PVI. We conducted a meta-analysis of available data to assess the incremental impact of PWI based on whether patients had paroxysmal or persistent (PAF, PeAF) AF.

Objective:
To evaluate the incremental impact of PWI following PVI in patients with PAF and PeAF.

Methods:
The online databases (Pubmed, Medline, Embase) were searched using the terms “pulmonary vein isolation”, “posterior wall isolation”, or “posterior wall ablation”. Out of 1843 studies, 11 met our strict criteria (Table). Specifically, patients were undergoing
de novo
ablation for treatment of PAF or PeAF using either cryoballoon or radiofrequency energy. Patients had PVI +/- PWI; studies that included additional ablations (except for cavotricuspid isthmus ablation) were excluded. The primary outcome was long-term freedom from recurrence of any atrial tachyarrhythmia (AT).

Results:
The cohort consisted of 1702 patients (65 ± 18 years, 75% male); 1404 (82%) pts with PeAF and 298 (18%) pts with PAF (Table). In the PeAF group, AT recurrence was significantly higher in patients who underwent PVI alone as compared to those who also had PWI (OR 1.85, 95% CI [1.23, 2.77], P = 0.003, Figure). In contrast, in the PAF group, outcome was similar in patients who did and did not undergo PWI in addition to PVI (OR 0.95, 95% CI [0.53, 1.72], P = 0.86, Figure).

Conclusions:
PWI was rarely used during the
de novo
ablation procedure in PAF patients and did not seem to impart additional benefit. In contrast, PeAF patients seemed to derive favorable impact from the addition of PWI to PVI. Additional randomized studies are needed to determine the role of PWI in PeAF patient undergoing de novo ablation for management of AF.
Abstract 12657: Clinical, Laboratory, and Coronary Plaque Predictors of Atherosclerotic Non-Response to Statin Therapy
Authors: van Rosendael Sophie E , van den Hoogen Inge J , Lin Fay Y , Andreini Daniele , Al-Mallah Mouaz H , Budoff Matthew , Cademartiri Prof. Dr. Filippo , Chinnaiyan Kavitha , Choi Jung Hyun , Conte Edoardo , Marques Hugo , Goncalves Pedro , Gottlieb Ilan , Hadamitzky Martin , Leipsic Jonathon , Maffei Erica , Pontone Gianluca , Raff Gilbert L , Shin Sanghoon , Kim Yong-Jin , Kwon Byoung , Chun Eun-Ju , Sung Ji Min , Lee Sang-Eun , Virmani Renu , Samady Habib , Stone Peter H , Min James K , Narula Jagat , Berman Daniel , Bax Jeroen J , Shaw Leslee J , Van Rosendael Alexander R , Chang Hyuk-Jae
Published: June 2023

Introduction:
Statins reduce major cardiovascular events, but residual risk remains. The study examined determinants of atherosclerotic statin non-response in patients using statins.

Hypothesis:
We hypothesized that a comprehensive evaluation of atherosclerosis identifies patients that progress atherosclerosis despite the use of statin therapy.

Methods:
The multi-center PARADIGM registry included patients who underwent serial CCTA ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up CCTA were included. Atherosclerotic statin non-response was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. A secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque.

Results:
We included 649 patients (62.0±9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin non-response. Age, diabetes, hypertension, and all atherosclerotic plaque features (high risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin non response, while only diabetes, the number of high risk plaque features, noncalcified and calcified PAV were independently associated with atherosclerotic statin non-response (OR:1.41 (0.95-2.11), OR:1.15 (1.09-1.21), OR:1.06 (1.02-1.10), OR:1.07 (1.03-1.12), respectively). For the secondary endpoint (N=125, 19.2%), only non-calcified PAV and number of HRP features were the independent determinants (OR:1.08 (1.03-1.13) and OR:1.21 (1.06-1.21), respectively).

Conclusions:
In patients treated with statins, baseline plaque characterization by plaque burden and high risk plaque is associated with atherosclerotic statin non-response defined as important progression of coronary atherosclerosis. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.
Abstract 12661: Prognostic Significance of Tubular Injury Biomarkers in Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Salman Oday , Qian Chenao , Cohen Jordana , Jehangir Qasim , Zamani Payman , Ebert Christina , Greenawalt Danielle , Wang Zhaoqing , Zhao Lei , Chang Ching-Pin , Gordon David A , Ramirez-Valle Francisco , Cappola Thomas P , Chirinos Julio A
Published: June 2023

Background:
The onset and progression of CKD in HFpEF may be driven by different etiologies, including tubular injury, glomerular disease or interstitial remodeling. We assessed the prognostic significance of tubular injury assessed with a combination of plasma protein biomarkers.

Methods:
We analyzed data and samples from the TOPCAT trial. We utilized the SomaScan assay to measure tubular injury biomarkers: Alpha-1 microglobulin (A1M), Beta 2 microglobulin (B2M), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule 1 (KIM1), and interleukin 18 (IL-18). Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between factor scores and: (1) All-cause mortality; (2) The composite of death or heart failure hospital admission (DHFA). All hazard ratios (HR) are standardized (per unit increase in z score) to facilitate comparisons. Linear regression was used to assess the relationship of each factor to 4,746 other proteins, followed by pathway analyses.

Results:
There were 2 underlying factors: factor 1 was associated predominantly with KIM1, whereas factor 2 was strongly associated with NGAL. Both factors were associated with estimated GFR. Factor 1 was predominantly associated with diabetes, whereas factor 2 was predominantly associated with a lower mean arterial pressure. In a model that included the 2 factors, both were significantly and independently associated with DHFA (Factor 1 HR=1.75; 95%CI=[1.47,2.07]; P<0.0001; Factor 2 HR=1.37; 95%CI=[1.17,1.62]; P=0.0001), but only factor 1 was significantly associated with death (Factor 1 HR=1.22; 95%CI=[1.06,1.40]; P=0.0046; Factor 2 HR=1.23; 95%CI=[0.98,1.54]; P=0.066). In analyses that adjusted for estimated GFR and the MAGGIC risk score, Factor 1 was significantly associated with death and DHFA, whereas Factor 2 was only associated with DHFA. These factors were associated with pathways related to immunity, fibrosis, oxidative stress, cell death, and myocardial remodeling.

Conclusion:
Tubular injury is associated with adverse outcomes in HFpEF. This relationship is independent of baseline GFR, suggesting that ongoing injury contributes to poor outcomes and may represent a target for therapy.
Abstract 12665: Using Healthcare Claims Data and Machine Learning to Identify Health Disparities for Individuals With Diagnosed and Undiagnosed Familial Hypercholesterolemia
Authors: Ahmad Zahid , Xing Chao , Khera Amit , Huang Chun-Yuan , Brandt Eric , MacDougall Dianne , Ahmed Catherine D , McGowan Mary P , Wilemon Katherine A , Myers Kelly
Published: June 2023

Introduction:
Individuals with Familial Hypercholesterolemia (FH) warrant intensive lipid lowering therapy starting with statins and adding ezetimibe and PCSK9 inhibitors (PCSK9i) as needed to achieve LDL-C treatment targets. Little data exists on whether disparities exist in the US FH population for ezetimibe, PCSK9i or the combination of statins + ezetimibe + PCSK9i.

Methods:
We queried the Family Heart Database, a healthcare claims database from the Family Heart Foundation, for filled prescriptions for statins, ezetimibe, and PCSK9i in patients with an ICD-10 diagnosis of FH (E.78.01) as well as undiagnosed FH patients (Probable FH) identified by the Family Heart Foundation’s FIND-FH® machine learning algorithm. Data were analyzed in multivariable models including age, education, income, race/ethnicity, and gender.

Results:
Among 77,671,959 individuals, 280,426 had an ICD-10 diagnosis of FH (51% female, 79.5% White, 11.8% Black, and 8.7% Hispanic) and 899,027 had Probable FH (48% female, 78.7% White, 12.9% Black, and 8.5% Hispanic). Diagnosed and Probable FH males were 46% and 48% more likely, respectively, than females to receive high intensity statins. Individuals in the $100,000+ income bracket - both the diagnosed and Probable FH groups - were 30 to 50% more likely to receive ezetimibe, PCSK9i, or statin + ezetimibe + PCSK9i (Table). The highest education level was associated with 51% higher odds of statin + ezetimibe + PCSK9i use in diagnosed FH patients. Whites were 6-30% more likely to get ezetimibe, PCSK9i, and the combination of statin + ezetimibe + PCSK9i compared to Blacks.

Conclusions:
Real world patterns of medical care reveal appropriate lipid lowering therapy is more often prescribed for individuals with FH who are White, have high income, or have advanced education. Efforts are warranted to improve equity and provide all individuals with FH an opportunity for cardiovascular risk reduction.
Abstract 12670: The End-of-Life Experience of Pediatric Vad Patients: A Report From the Action Registry
Authors: Hollander Seth A , Pyke-Grimm Kimberly , Shezad Muhammad F , Zafar Farhan , Cousino Melissa , Feudtner Chris , Char Danton
Published: June 2023

Introduction:
Although most pediatric VAD patients survive to transplantation, some die on device therapy. The end-of-life experience of pediatric VAD patients is not well characterized.

Hypothesis:
Invasive interventions are common in pediatric VAD patients at the end-of-life.

Methods:
Retrospective review of pediatric VAD patients in the ACTION registry who died on device therapy between 3/2012-9/2021. Demographic and clinical data, including invasive interventions used at the end-of-life and the location of death, were analyzed.

Results:
107/721 (15%) of patients died on device at a median age of 5 years (IQR:1, 16) at 43 days (IQR: 17, 91) post implant. Goals of VAD therapy were bridge to candidacy for 50 patients (51%), bridge to transplant for 44 (37.6%), destination therapy for 2 (1.7%). The most common cause of death was multi-organ failure (n=35, 30%), followed by infection (n=12, 10.3%). Eighty-five of 92 patients (92.4%) died with a functioning device in place. Most patients were receiving invasive interventions (mechanical ventilation, 75%; vasoactive infusions, 62%) at the end-of-life. (
Table 1
). Only 10 (9%) patients died at home. Utilizing these data, we identified and estimated the frequency of four common end-of-life trajectories for pediatric VAD patients. (Figure 1).

Conclusions:
Aggressive interventions are common at the end-of-life of pediatric patients with VADs. Dying at home is uncommon. Identification of common end-of-life patterns will serve as an outcome measure and inform future practices to promote informed patient and provider decision-making to reduce suffering in those who die on device support.
Abstract 12677: Intensive Cardiac Rehabilitation Outcomes in Patients With Heart Transplant
Authors: Jafri S. Hammad , Ngamdu Kyari Sumayin , Baig Muhammad , Freeman Andrew M , Ornish Dean , Morrison Alan R , Wu Wen-Chih H
Published: June 2023

INTRODUCTION
Heart Transplant (HT) is gold standard for patients with Heart failure (HF) with end stage disease, however it requires ideal post-surgical recovery which includes medications & Cardiac Rehabilitation (CR). Clinical trials have shown that CR can reduce morbidity & mortality, increase exercise tolerance and reduce psychological symptoms in patients with HT. Intensive Cardiac rehabilitation (ICR) has proven benefits for patients with HF but the outcomes of ICR in patients with HT are unknown.

Methods:
Retrospective cohort study of 1413 patients from Jan-2016 to Dec-2020. ICR sessions consists of 4-hours two times per week for 9-weeks of lifestyle modification aiming at high fiber low fat diet, peer support, exercise and stress reduction.Patients were divided into two groups: 18 patients in HT group and 1395 patients in HF group. Primary endpoints were change in body mass index (BMI), exercise minutes per week (EMW) and depression scores (CESD). Secondary endpoints includes change in blood pressure (BP), cholesterol (chol), low density lipoprotein (ldl), high density lipoprotein (hdl), triglycerides (tgl) and health status (SF-36 physical & mental composite scores). T test was used to compare variables between two groups. Linear regression was used to adjust for difference in baseline variables.

Results:
Table 1
explains baseline characteristics and demographics of both groups.
Table 2
shows outcomes of both groups pre and post-ICR.

Conclusions:
Significant Improvement in ICR outcomes were achieved for both groups. There is no difference among groups when improvements were compared with each other except for chol which has improved more in patients with HF.