bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10348: Contemporary Management of Cardiac Implantable Electronic Device Infection: A Survey of American College of Cardiology Members and Primary Care Physicians (COGNITO Study)
Authors: Sood Ami , Birgersdotter-Green Ulrika , Lakkireddy Dhanunjaya , Rao Archana , Theriot Paul
Published: June 2023

Introduction:
Cardiac implantable electronic devices (CIED) infection remains a serious complication associated with CIEDs. Complete extraction is a Class I recommendation for CIED infections, but a recent US Medicare analysis has demonstrated that there is a lack of guideline adherence with only 1 in 5 patients with a CIED infection undergoing extraction.

Objective:
To assess the current practice of US-based physicians related to the diagnosis and management of CIED infections and explore potential barriers to extraction.

Methods:
ACC performed a survey, based on a previous multinational EHRA/ESC needs assessment, to collect data from a mix of US physicians that may encounter CIED patients with complications. The survey timeframe was Feb 11 - Mar 10, 2022. Sampling techniques and screener questions were used to determine eligibility. The survey included questions based on knowledge and experience with CIED infection patients and multiple case scenarios.

Results:
The response rate was 20%, with a total of 387 physicians completing the survey. Less than half of clinicians polled (49%) indicated that they were familiar with the current HRS/AHA/EHRA/ESC guidelines regarding CIED infection. EPs (91%) were more familiar with these guidelines, compared to non-EP cardiologists (29%) and PCPs (23%). All EPs surveyed have had experience managing patients with CIEDs and nearly all (98%) have implanted these devices. Only two-thirds of non-EP cardiologists have experience with these patients. Only 30% of physicians specified that their institution had guideline-based protocols in place for managing patients with CIED infection. When presented with pocket infection cases, close to 50% of non-EP cardiologists and 70% of PCPs did not recommend guideline directed treatment.

Conclusions:
There are gaps in familiarity of guidelines as well as practical management of CIED infection with several non-extracting physician groups. Additionally, there is a lack of care pathways and other mechanisms in place for the management of CIED infection patients at most institutions. Addressing discrepancies, including guideline education and streamlining care/referral pathways, will be a key factor to bridging the gap and improving CIED infection patient outcomes.
Abstract 10355: Allostatic Load and Cardiovascular Outcomes in Males With Prostate Cancer
Authors: Stabellini Nickolas , Cullen Jennifer , Moore Justin , Cao Lifen , Weintraub Neal L , Harris Ryan A , Wang Xiaoling , Datta Biplab , Garcia Jorge , Shanahan John , Hamerschlak Nelson , Waite Kristin , Terris Martha , Fillmore Nathanael , Montero Alberto , Barnholtz-Sloan Jill , Guha Avirup
Published: June 2023

Introduction:
Prostate cancer (PC) is the leading type of newly diagnosed cancer in males. Cardiovascular disease (CVD) is the leading cause of death in men with PC. Accumulated stress, which is triggered by multiple environmental factors and life events, plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL).

Hypothesis:
We hypothesize that AL is associated with the development of major cardiac events (MACE) after the diagnosis of PC.

Methods:
Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2019. AL was modeled as an ordinal variable from 0 to 11. Fine and Gray competing risk regression model accounting for the competing risk of all-cause mortality were used to calculate the impact of pre-cancer diagnosis AL and post-diagnosis AL in 2-year major cardiac events (MACEs). The effect of AL variation over time on MACEs development was calculated via the piecewise Cox Regression model where the time periods considered were before PC diagnosis, 2 months after, 6 months after and 1-year after PC diagnosis.

Results:
We analyzed 5,261 (19,840 person-years) PC adenocarcinoma patients, of which 6.6% (N=347) had a 2-year MACE. For every 1 point increase in AL before PC diagnosis and within 60 days after PC diagnosis the risk of MACE increased 25% (adjusted Hazards Ratio [aHR] =1.25, 95% Confidence Interval [CI] = 1.18-1.33), and 27% (aHR=1.27; 95% CI = 1.20-1.35), respectively. Using AL as a time varying exposure, the risk of MACE increased 19% (aHR=1.19, 95% CI 1.11-1.27), 22% (aHR=1.22, 95% CI 1.14-1.33), 28% (aHR=1.28, 95% CI 1.23-1.33), and 31% (aHR=1.31, 95% CI 1.27-1.35) for every 1 point increase in AL before PC diagnosis, 2 months after, 6 months after and 1-year after PC diagnosis, respectively.

Conclusion:
AL and its variation over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC. Preventive measures to minimize AL may require collaboration between cancer control and cardio-oncology.
Abstract 10380: A Case of Statin-Induced Necrotizing Autoimmune Myopathy After Covid-19 Vaccination
Authors: Verma Gagan , Arjonilla Marta , Gier Chad , Chen On
Published: June 2023

Introduction:
Statins have become the most prescribed medications in the United States. We examine the case of a woman who developed statin induced necrotizing myopathy after receiving the Pfizer COVID-19 vaccine after 15 years of statin use.

Case:
A 67-year-old woman with history of hypothyroidism, hyperlipidemia, and a remote history of breast cancer, treated with surgical excision, presented with a two-month history of progressive proximal muscle weakness in all four extremities. During this time, she noticed unusual difficulty in her habitual exercise routine, culminating in being suddenly unable to walk or lift her arms. Prior to the onset of her symptoms, she reported that she had received the Pfizer COVID-19 booster vaccine. She had been adherent to her daily medications for over fifteen years (atorvastatin 20mg and levothyroxine 75mcg). Labs revealed creatine phosphokinase of 10,354. Muscle biopsy of the thigh was indicative of necrotizing myopathy. 3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were elevated at over 200 units, suggesting an immune-mediated myopathy. She was treated with intravenous immune globulin and placed on a prednisone taper. Her strength improved, and she was discharged home with physical therapy.

Discussion:
Statin-induced necrotizing autoimmune myopathy (SNAM) is a rare manifestation of autoimmune myositis. In the anti-HMG-CoA reductase subtype, the immune system is sensitized to HMG-CoA reductase resulting in immune-mediate cellular injury. The duration of exposure to statins prior to development of SNAM varies from 2 months to 10 years, with an average of 3 years. Our patient had previously been on statin therapy for 15 years without issue and subsequently developed SNAM after receiving a COVID-19 booster. This highlights the possibility that ribonucleotide vaccines, in particular COVID-19, may stimulate immune-mediated autoantibody formation and lead to increased risk for SNAM in patients on statin therapy. These patients would benefit from alternative lipid lowering therapies, such as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors.
Abstract 10403: Residual Lesion Severity is Associated With Adverse Neurodevelopmental Outcomes in Young Children With Congenital Heart Disease
Authors: Sengupta Aditya , Gauvreau Kimberlee , Sadhwani Anjali , BUTLER SAMANTHA C , Newburger Jane W , Del Nido Pedro J , Nathan Meena
Published: June 2023

Introduction:
There are few modifiable risk factors for adverse neurodevelopmental (ND) outcomes in congenital heart disease. We assessed the Residual Lesion Score (RLS), a quality improvement metric that assesses residual lesion severity following congenital heart surgery (CHS), as a predictor of ND delay.

Hypothesis:
We hypothesized that RLS would be independently associated with ND outcomes.

Methods:
This was a single center, retrospective review of patients who underwent CHS from 01/2011-12/2019 and received post-discharge ND evaluation between the ages of 12 and 42 months using the Bayley Scales of Infant Development, 3
rd
ed. (BSID-3). RLS was assigned at discharge per previously published criteria: Class 1, no residua; Class 2, minor residua; Class 3, major residua or in-hospital unplanned reintervention. Associations between RLS and BSID-3 scores (at the first ND evaluation) were evaluated using linear regression, adjusting for baseline patient risk, the Childhood Opportunity Index, and maternal education level. Linear mixed effects models assessed trends in ND outcomes over time.

Results:
Of 477 patients with mean age at ND testing of 21.2 ± 6.1 months, 282 (59.1%), 132 (27.7%), and 63 (13.2%) patients had RLS 1, 2, and 3 lesions, respectively.
Table 1A
shows BSID-3 outcomes by RLS. On multivariable analysis, Class 3 patients had significantly lower cognitive, receptive and expressive communication, and fine and gross motor scaled scores, compared to Class 1 patients, with the largest difference observed in the cognitive domain (
Table 1B
). In a subset of 191 patients with more than one ND evaluation, Class 3 patients made fewer gains in skills from the first to the last evaluation in the cognitive and language domains, compared to Class 1 patients (both p<0.05).

Conclusions:
Patients with major residua (RLS 3) are at increased risk for ND delay, warranting closer ND follow-up and greater developmental support for cognitive, communication, and motor skills.
Abstract 10413: Obesity Modifies Clinical Outcomes of RV Dysfunction
Authors: Ma Janet , Zern Emily , Wang Dongyu , Rambarat Paula , Pomerantsev Eugene , Picard Michael , Ho Jennifer E
Published: June 2023

Introduction:
Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. Whether this association is modified by obesity is unclear. We examined the association of obesity with hemodynamic indices of RV function, and subsequent outcomes.

Hypothesis:
We hypothesized that obesity is associated with RV dysfunction, and that obesity modifies the association of RV dysfunction with adverse clinical outcomes.

Methods:
We examined patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction [pulmonary artery pulsatility index (PAPi), right atrial pressure: pulmonary capillary wedge pressure ratio (RAP:PCWP), RV stroke work index (RVSWI)]. Cox models examined the association with clinical outcomes.

Results:
We studied 8285 patients (mean age 63 years, 40% women). Higher BMI was associated with worse indices of RV dysfunction, including lower PAPi (β -0.26, SE 0.01, p <0.001) and higher RA:PCWP ratio (β 0.25, SE 0.01, p-value <0.001) but not RVSWI (p>0.05). Over 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure (HF) hospitalization events. RV dysfunction was associated with greater risk of mortality (PAPi: HR 1.11 per 1-SD increase, 95% CI 1.04-1.18; RA:PCWP ratio: HR 0.84, 95% CI 0.79-0.90), with similar associations with risk of HF hospitalization. Furthermore, BMI modified the effect of RV dysfunction on outcomes (P-interaction <=0.005 for both), and the effect of RV dysfunction was more pronounced at higher BMI.

Conclusions:
Patients with obesity had worse indices of RV function, including lower PAPi and higher RAP:PCWP ratio. While RV dysfunction was associated with worse clinical outcomes, this association was especially pronounced among individuals with higher BMI.
Abstract 10481: The Effect of Current Smoking on Platelet Reactivity Measures by Point-of-Care Methods in Patients Treated With and Without Clopidogrel
Authors: Nicolau Jose C , Salsoso Rocio , Dalcoquio Talia , Gurbel Paul A , Tantry Udaya , Giugliano Robert , Nakashima Carlos A , Franci Andre , Rizzo Paulo , menezes fernando , Guardieiro Bruno , Scanavini Filho Marco Antonio , Ferrari Aline G , Pereira Cesar , Arantes Flavia B , Barbosa Carlos , Bertolin Adriadne , Furtado Remo
Published: June 2023

Introduction:
Smoking is associated with worse response to P2Y12 inhibitors. However, the relationship between smoking, platelet reactivity (PR) and traditional risk factors for atherosclerosis is unclear.

Hypothesis:
To analyze the relationship between smoking, PR and risk factors for atherosclerosis.

Methods:
A prospective databank of 13 research protocols was retrospectively analyzed. Among 1260 patients included in the analysis, 299 were smokers; 721 had acute coronary syndromes (521 with clopidogrel), and 539 had stable coronary artery disease (4 with clopidogrel). The association between smoking and PR analyzed by Multiplate-ADP (MPADP) and VerifyNow-PRUTest (VNPRU), inflammatory markers (leukocytes and hs-C-reactive protein), creatinine, HbA1c, total cholesterol, HDL-c, LDL-c and triglycerides, was analyzed in univariate and multivariable models. PR results were analyzed as continuous and categorical variables (bellow or above the median).

Results:
Unadjusted results for the comparison between smokers and non-smokers are depicted in the Table and Figure. In adjusted models, the significant associations between smoking and PR were maintained: 1) MPADP Odds-Ratio (OR)=0.984, p<0.001; 2) VNPRU OR=0.996, P=0.008; 3) MPADPCAT>MD OR=0.450, P<0.001; 4) VNADPCAT>MD OR=0.408, p<0.001; 5) ADPMEDIAN>MD OR=0.394, p<0.001). HDL-c (negative) was the only risk factor for atherosclerosis that correlated independently with smoking in all adjusted models, with leukocytes (positive) and creatinine (negative) showing correlation in 4 of the 5 models.

Conclusion:
Smoking is independently associated with lower PR and HDL-c levels.
Abstract 10532: Physician Interpretation and Characterization of Intracardiac Electrograms at the Time of Non-Cardiac Death
Authors: Kikuchi Daniel S , Kiani Soroosh , Bhatia Neal K , Ibrahim Rand , Merchant Faisal M , Suresh Mithun , Shah Anand D , El-Chami Mikhael F , Leon Angel R , Lloyd Michael S
Published: June 2023

Introduction:
Electrograms (EGMs) generated by implantable cardiac devices at the time of non-cardiac death may have artifact from non-arrhythmic sources, such as coagulated blood and air bubbles. While few studies have described the nature of terminal EGMs in non-cardiac death, it is clinically and medicolegally important to characterize these EGMs to elucidate events that may otherwise be misinterpreted as device failure. Here we investigated terminal EGM features that may aid clinicians in discerning cardiac from non-cardiac death.

Methods:
Terminal EGMs were analyzed by independent physician reviewers. Deaths were adjudicated as non-cardiac based on direct clinical data at the time of death using a modified Cardiac Arrhythmia Suppression Trial approach. In total, 16 non-cardiac terminal EGMs were identified and compared to a control cohort of true arrhythmic events. Using a subset of identified EGMs, an 8-question survey was administered to electrophysiologists blinded to cause of death. Several variables were identified as important for the correct classification of EGMs. The statistical performance of each variable for detecting non-cardiac death and true arrhythmias in our sample was evaluated. These results were shared, and the survey was readministered.

Results:
In our sample, absence of organized atrial activity had a sensitivity (SN) of 78.5%, specificity (SP) of 100%, and positive predictive value (PPV) of 100% for non-cardiac terminal EGMs. Cycle length <130 ms and absence of discernible deflections both had SPs and PPVs of 100% for non-cardiac death but were less sensitive (60% and 20%, respectively). An abrupt change following therapy and response to therapy both had SNs, SPs, and PPVs of 100% for true arrhythmias. Survey response rate was 68.8% and 62.5% for the pre- and post-survey, respectively. Pre-survey scores ranged from 50 – 87.5% correct with a mean of 72.7%. Post-survey scores ranged from 75 – 100% with a mean of 86.3% (p< 0.01).

Conclusions:
There is variability and inaccuracy among expert physicians' interpretation of EGMs during non-cardiac death. The variables identified in this study will aid in the development of a clinical risk score used to discern non-cardiac death and true device malfunction based on terminal EGMs.
Abstract 10535: Relation of Multiple Low-Risk Lifestyle Behaviors With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Chen Victoria , Khan Tauseef A , Ahmad Suleman , Lee Danielle , Wang Lily , Gallienne Charlotte , Blanco Mejia Sonia , Field David , Poirier Paul , Lau David C , Leiter Lawrence A , Kendall Cyril , Sievenpiper John L
Published: June 2023

Introduction:
The association of combined low-risk lifestyle behaviors (LRLBs) with cardiovascular disease (CVD) and all-cause mortality has not been systematically quantified.

Objective:
We undertook a systematic review and dose-response meta-analysis to assess the association of combined LRLBs with CVD and all-cause mortality.

Methods:
MEDLINE, EMBASE and Cochrane were searched up to December 29, 2021. Prospective cohort studies reporting the association between a minimum of 3 combined LRLBs (including healthy diet) with CVD, coronary heart disease (CHD) and stroke incidence and mortality were included. Independent reviewers extracted data and assessed study quality. Highest vs. lowest LRLB score was pooled using random effects. Heterogeneity was assessed (Cochran Q) and quantified (I
2
). Global dose response meta-analysis (DRM) for maximum adherence was estimated using one-stage linear mixed model. The certainty of the evidence was assessed using GRADE.

Results:
116 cohort comparisons (n=9,775,191) involving 382,922 cases were included. Comparing highest with lowest adherence LRLBs were associated with lower risk of CHD incidence (RR, 0.29 [95% CI, 0.21, 0.42]), stroke incidence (0.56 [0.50, 0.62]), CVD incidence (0.47 [0.37, 0.58]), CHD mortality (0.32 [0.25, 0.41]), stroke mortality (0.37 [0.30, 0.46]), CVD mortality (0.41 [0.34, 0.49]) and all-cause mortality (0.46 [0.41 to 0.52]). DRM analysis showed a linear association between LRLBs and all outcomes reaching a global DRM between 59-76% protection. LRLBs were defined with variable ranges as a healthy body weight (body mass index <30kg/m
2
), healthy diet (healthy diet score >median), regular physical activity (1/week to >30 minutes/day), smoking cessation (never smoked or smoking cessation), light alcohol intake (≤30g/day) and adequate sleep (5.5-9 hours). The certainty of the evidence was graded as moderate to high owing to downgrades for inconsistency and/or upgrades for a large magnitude of effect and significant dose-response gradient.

Conclusions:
Pooled analyses show that the combination of LRLBs was associated with a substantial lower risk of CVD outcomes and all-cause mortality. The available evidence provides a very good indication of the benefit of combined LRLBs.
Abstract 10573: Left Ventricular Structure, Function, and Clinical Outcomes in Methamphetamine-Associated Heart Failure
Authors: Cedarbaum Emily R , Durstenfeld Matthew S , Win Sithu , Haas Brian , Davis Jonathan D , Wu Alan H , Li Danny , Swaminathan Shreya , Arechiga Victor , Wang Teresa , Hsue Priscilla Y
Published: June 2023

Introduction:
Methamphetamine use and overdose deaths are increasing. People who use methamphetamine are at risk for methamphetamine-associated heart failure (meth-HF). Cardiac fibrosis has been reported in nonischemic cardiomyopathies, but the role of cardiac fibrosis and other factors underlying the pathophysiology and reversibility of meth-HF remain unknown.

Methods:
Participants with meth-HF were recruited into a prospective cohort at a safety net hospital in San Francisco. Data collection included medical history, clinical outcomes, longitudinal echocardiograms (TTEs), markers of inflammation and fibrosis, and cardiac magnetic resonance imaging (CMR). Outcomes included mortality, changes in LVEF, and hospital readmission.

Results:
Forty-six participants enrolled: median age 51 years, 83% male, 41% Black, 20% Asian, 33% unstably housed, 76% actively using methamphetamine. Baseline TTEs demonstrated LV dilation (median LVIDd 5.7cm, LVIDs 4.7cm) and severely reduced LV systolic function (LVEF<30% in 62%). After median 9 months follow-up, 13% were deceased. Compared to survivors, baseline LV dimensions were larger (mean LVIDd 6.7 vs 5.5cm, p<0.05; LVIDs 6.1 vs 4.5cm, p<0.05) and LVEF was lower (mean 19% vs 29%, p<0.05) among those who died. At baseline, smaller LV size, higher LVEF, and guideline-directed medical therapy (GDMT) were more common in those with LVEF improvement >10% (Fig). CMRs were often abnormal with late gadolinium enhancement and elevated extracellular volume, but there was no clear association with LV recovery.

Conclusions:
Despite their young age, the meth-HF population has a high mortality rate and severely reduced LVEF with LV dilation. Smaller LV size, higher LVEF, and GDMT were more common in those with LVEF improvement. These findings suggest that early identification and treatment of heart failure in people who use methamphetamine, along with drug cessation, may be associated with reversibility and improved outcomes.
Abstract 10655: Collagen Remodeling, Inflammatory Biomarkers and Fatty Acid Regulation in Understanding the Molecular Pathogenesis of Atrial Fibrillation
Authors: Odeh Ameer , Dungan Gabriel , Siddiqui Fakiha , Iqbal Omer , Bontekoe Emily , Hoppensteadt Debra , Steen Lowell , Fareed Jawed , Syed Mushabbar
Published: June 2023

Introduction:
Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling, inflammatory pathways and fatty acid dysregulation are believed to play a role in the development of AF.

Hypothesis:
This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups.

Methods:
Sandwich ELISA kits were used to quantify the collagen remodeling proteins, various inflammatory biomarkers and liver type fatty acid binding protein (L-FABP) in the clinically diagnosed AF population (n=78) and the control population (n=50). Non-stratified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism.

Results:
We found significant upregulation in all the biomarkers in the AF cohort was noted in comparison to the control group. The collagen remodeling biomarkers included MMP-1, MMP-2, TIMP-1, TIMP-2, PICP, PINP, PIIICP, PIIINP and ICTP. All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The inflammatory biomarker TNFa was also elevated in AF compared to the control group. The fatty acid dysregulation biomarkers, L-FABP and NEFAs, were elevated in AF patients as well. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r=0.47, p<0.001), NEFA and TIMP-2 (r=0.41, p=0.002), NEFA and ICTP (r=0.41, p=0.002), and NEFA and PIIINP (r=0.61, p<0.0001).

Conclusions:
The elevation of all the collagen remodeling biomarkers indicates that there is an upregulation of collagen degradation and deposition in AF which could be contributing to atrial fibrosis. The higher TNFa levels indicate that inflammation could also play a role in the pathogenesis of AF. Fatty acid dysregulation biomarkers, including L-FABP and NEFAs, were elevated in AF patients reinforcing the hypothesis that excess fatty acids could also be contributing to atrial fibrosis and epicardial adipose tissue formation.
Abstract 10708: Dietary Methionine Restriction Protects Against Abdominal Aortic Aneurysm via Amino Acid Starvation Response
Authors: Yin Li , Shirasu Takuro , Huang Yitao , Kent Eric W , Zhang Mengxue , Hoyt Nicholas , Gregg Alexander C , Riccio Alessandra M , Guo Lian-Wang , Wang Bowen
Published: June 2023

Introduction:
Dietary intervention emerges as a promising non-medicinal avenue for the treatment of a wide range of diseases. Limiting the intake of single amino acid has been shown to produce health benefits similar to that of calorie restriction yet without significant risks of malnutrition. One of the established regimen, methionine restriction (MR), was recently shown to confer pleiotropic benefits in cardiometabolic disease models, largely attributed to the activation of the GCN2-mediated amino acid starvation response pathway. However, the therapeutic and mechanistic implications of dietary amino acid restriction remain unknown in abdominal aortic aneurysm (AAA), a lethal vascular disease that is without a cure other than the traumatic surgical repairs. Herein, we sought to probe the outcome of MR as well as the role of GCN2 in AAA.

Methods and Results:
Following a 2-week pre-treatment with MR (20% methionine level) or iso-caloric control diet, male Sprague Dawley rats were subjected to intraluminal elastase perfusion. At day 7, animals in the MR group showed significantly less aneurysmal dilation in comparison to control. To investigate the contribution from the GCN2-mediated amino acid starvation response, we subjected animals to the same dietary regimen of MR or control, followed by GCN2 silencing in the elastase-challenged aortic segments through localized infusion with GCN2-targeting or scrambled shRNA lentivirus. Indeed, tuning down aortic GCN2 effectively compromised the benefits exerted by MR against AAA. Finally, we determined whether GCN2 constitutes an intrinsic protector against aortic degeneration using GCN2 knockout mice (

Gcn2
-/-

). Following periaortic elastase challenge and β-aminopropionitrile treatment, Gcn2
-/-
mice displayed exacerbated expansion of aneurysmal lesions in comparison to Gcn2
+/+
control mice at day 28 post procedure.

Conclusions:
Our study provides the first experimental evidence supporting a potential role of dietary amino acid restriction (e.g., MR) in the prevention of AAA development. Additionally, GCN2-mediated amino acid starvation response possibly underlies the anti-AAA benefit exerted by MR and serves as an intrinsic protector against AAA pathogenesis.
Abstract 10745: Return to Play After Covid-19 Infection: Cardiac Imaging Findings in Youth
Authors: Yin Suellen M , bachman jennifer , Dionne Audrey , Friedman Kevin G , Newburger Jane W , Gauthier Naomi , Shafer Keri M , Castellanos Daniel A , Baker Annette L , Atwood Sarah , Burke Patricia , Alexander Mark E , De Ferranti Sarah D
Published: June 2023

Introduction:
SARS CoV2 has been associated with acute and subacute myocarditis. Screening after COVID-19 has been recommended prior to returning to physical activity. The yield of such investigations, particularly in youth, remains unknown.

Methods:
Retrospective chart review was performed of patients evaluated in a cardiology clinic for return to play (RTP) after COVID-19 between 01/20 - 06/21. Iteratively updated guidance for testing was provided to ambulatory providers. Patients with MIS-C were excluded. We reviewed demographics, clinical evaluation, and cardiac imaging.

Results:
Of 429 patients (age 16.3 ± 2.7 [range 8-21] yrs, 44% male) evaluated including 9 with pre-existing heart disease, 318 underwent echocardiograms and 23 also had cardiac MRI. Cardiac MRI was performed for abnormal screening ECG or echocardiogram or cardiovascular symptoms. New echocardiographic abnormalities were detected in 69 patients: 4 were possibly related to COVID-19 infection, 3 were new structural heart disease (2 anomalous coronary, 1 bicuspid aortic valve), and 62 were normal variants or trivial findings. New ventricular dysfunction (right or left, qualitative dysfunction or LV ejection fraction [EF] <55%) was noted in 11 patients (LV EF mean 52.7 ± 2.6%, minimum 46%). Eight underwent cardiac MRI confirming trivial to no ventricular dysfunction and none of the 23 MRIs demonstrated late gadolinium enhancement or met Lake Louise criteria for myocarditis. All patients without new diagnoses of structural heart disease were ultimately deemed safe to return to previous levels of physical activity.

Conclusions:
Cardiovascular evaluation for RTP of youth after COVID-19 demonstrated mild transient abnormalities and incidental findings, but no diagnoses of myocarditis. These data suggest early concerns about subclinical myocarditis may have been overestimated. Future studies should consider the costs and benefits of current society algorithms for such evaluations.
Abstract 10861: Temporal Trends in Cardiovascular Disease Among Asian American Subgroups
Authors: Nguyen Kaylin T , Li Jiang , Peng Allison , Heidenreich Paul A , Palaniappan Latha , Yong Celina M
Published: June 2023

Introduction:
Asians represent the fastest growing race/ethnic group in the U.S. Yet there is limited data differentiating the prevalence of cardiovascular disease among diverse Asian and mixed-race subgroups.

Methods:
Patients receiving care from a mixed-payer health care organization in Northern California between 2007-2018 were classified into self-identified race/ethnic subgroups. Cardiovascular disease diagnoses were identified from ICD-9 and ICD-10 codes. Cardiovascular disease prevalence over time was compared for each racial subgroup to Non-Hispanic White (NHW) with logistic regression models, which evaluated the interaction between race and year (continuous variable), controlling for age and gender.

Results:
Among 3,494,071 patient-years (56% female, mean age 49 years
+
17), prevalence of cardiovascular disease increased faster among all Asian subgroups, except Japanese and Native Hawaiian/Pacific Islander, compared to NHW (adjusted, p<0.01 for each) (
Figure
). Among all subgroups, Filipinos had the highest overall cardiovascular disease prevalence, which increased from 32.2% to 45.1% over the study period (reference: increase from 16.5% to 21.9% among NHW, p=.002). Among subcategories of disease, the prevalence of hypertension increased faster compared to NHW in every subgroup other than Japanese (Native Hawaiian/Pacific Islander p=0.045, p<0.01 for other subgroups). Coronary artery disease prevalence also increased faster among Asian Indian, Chinese, Filipino subgroups compared to NHW (p<0.0001 for each). However, myocardial infarction prevalence increased slower in Chinese and Korean subgroups compared to NHW (p=0.045 and p=0.02, respectively).

Conclusion:
Analysis of disaggregated Asian subgroups and mixed-race groups demonstrate the diversity of evolving cardiovascular disease prevalence over time, suggesting the importance of tailored approaches to reducing cardiovascular disease among racial subgroups.
Abstract 10875: Metabolic Reprogramming of the Failing Fetal Heart in Twin-Twin Transfusion Syndrome
Authors: Parchem Jacqueline G , Fan Huihui , Mann Lovepreet K , Chen Qiuying , Won Jong Hak , Gross Steven S , Zhao Zhongming , Taegtmeyer Heinrich , Papanna Ramesha
Published: June 2023

Adult heart failure is associated with reactivation of the fetal metabolic program, including impaired mitochondrial oxidative phosphorylation and a shift toward glycolysis. In the fetus, the metabolic response to cardiac stress is less clear. We used twin-twin transfusion syndrome (TTTS) as a model to uncover metabolic adaptations of the fetus to cardiovascular stress. TTTS is a unique complication that occurs in monochorionic-diamniotic twins (one placenta, two amniotic sacs) when unequal blood flow between twins within the shared placenta is the set up for donor-recipient physiology (Fig 1a). This circulatory imbalance is detected by sonographic signs of donor hypovolemia and recipient hypervolemia. We analyzed second trimester amniotic fluid to identify alterations in metabolism of TTTS recipient twins (n=22) vs. singleton controls (n=10) using untargeted metabolomics (LC/MS). All TTTS cases were severe (stage III; abnormal Dopplers indicating increased afterload and/or right heart failure). Due to dilution of amniotic fluid molecules in TTTS, data for each sample was normalized to protein concentration. Evaluation of differential metabolites in TTTS cases revealed two distinct clusters of disease (Fig. 1b). Compared with TTTS cluster 1 and controls, cluster 2 showed significantly increased lactate and alanine production, and evidence of redox stress (Fig. 1c). No differences in clinical characteristics or outcomes were observed between TTTS cluster 1 vs. 2 (maternal age, gestational age, fetal sex, disease severity, preterm birth, and perinatal death). Our findings reveal subclinical heterogeneity of stage III TTTS and suggest that some fetuses undergo metabolic reprogramming under conditions of cardiac stress, shifting even further toward energy-efficient glucose utilization. These differences in fetal response may represent different points along the same spectrum vs. inherent differences in the ability of fetuses to adapt to stress.
Abstract 10987: Acute Coronary Syndrome, Depression, and Anxiety in Female Patients
Authors: Liblik Kiera , Hu Ricky , Foldes-Busque Guillaume , Mulvagh Sharon , Sedlak Tara , Udell Jacob A , Kearn Natalie , Johri Amer
Published: June 2023

Introduction:
Female patients are significantly more likely than male patients to experience symptoms of depression and anxiety post-acute coronary syndrome (ACS), correlated with higher rates of cardiovascular morbidity and mortality. Yet, it is unclear if all female patients are impacted broadly or if specific subgroups of female patients are at elevated risk. We aimed to identify the cardiovascular and psychosocial variables correlated with increased depression and anxiety symptoms immediately post-ACS as well as at 3 and 6-month follow-up.

Hypothesis:
There is a combination of cardiovascular and psychosocial factors associated with elevated depressive/anxious symptoms (Hospital Anxiety and Depression Scale (HADS) score ≥8 on the depression/anxiety subscales) in female patients post-ACS.

Methods:
This was a prospective multi-center questionnaire-based clinical research study featuring data from 6 sites across Canada using a logistic regression model to delineate multivariate strength of association. Baseline visit (within 72 hours of ACS) included HADS and a sociodemographic questionnaire. Follow-up visits (3 and 6-months) include HADS, Cardiac Anxiety Questionnaire, new health events, mortality, Short Form-12 Health Survey, and Somatic Symptom Scale-8.

Results:
A total of 245 patients were included in analysis (Table 1). HADS-A≥8 was associated with increased health anxiety at baseline (OR6.56; p<0.001). Conversely, HADS-D≥8 was associated with low social support at baseline (OR3.35; p=0.005) and 3-month follow-up (OR22.65; p<0.001) as well as previous diagnosis of depression at 3-month (OR22.73; p<0.001) and 6-month (OR5.50; p=0.02) follow-up.

Conclusion:
We identify key factors associated with symptoms of depression and anxiety post-ACS in female patients. Developing a deeper understanding of the relationship between mental health and ACS will benefit patients by informing intervention and prevention strategies.
Abstract 10988: The Dynamic Duo of Electrical and Thyroid Storm Caused by Amiodarone
Authors: Sukhoo-Pertab Marc , Kuzyk Yuriy , Chua Rochelle Anne , Khanna Ashok , Khanna Ashok
Published: June 2023

Case description:
A 61 year-old male with a hx of CAD s/p CABG and HFrEF s/p AICD presents with a 4-day history of dizziness and shortness of breath; he was found to be in ventricular tachycardia (VT) storm. ICD interrogation was found to have 13 shocks in 24 hours. His thyroid function tests (TFT) were abnormal: TSH undetectable, elevated FT4 7.7 (0.93-1.7) and T3 246.6 (84-202) ng/dL, respectively. He was diagnosed with severe thyrotoxicosis, likely due to amiodarone-induced thyrotoxicosis (AIT) type 2 and a Burch-Wartofsky score of 50, highly suggestive of thyroid storm (TS). He was started on hydrocortisone, prednisone, propylthiouracil, and metoprolol for the TS. Procainamide drip had been initiated for VT and titrated until VT was controlled. Repeat TFTs in 48 hours showed no changes in TSH or FT4, but T3 had normalized. Procainamide and hydrocortisone were discontinued after VT frequency had decreased.

Discussion:
An electrical storm (ES) is a state of electrical instability characterized by multiple episodes of VT in 24 hours. In patients with ICD, it is defined as >3 anti-tachycardic pacing therapies or shock. Most patient with ES have severe underlying structural heart disease with various inciting events such as thyrotoxicosis. Amiodarone is the drug of choice in VT; however, complications such as AIT should be recognized. Thyroid hormone has a direct arrhythmogenic effect on the heart through various cellular mechanisms. In our patient, amiodarone was discontinued after the diagnosis of AIT. Procainamide and antithyroid therapy were started, which subsequently controlled the VT. Resistance to therapy can occur, and more elaborate interventions such as plasmapheresis are an option to remove amiodarone, its metabolites, and free thyroid hormones.

Conclusion:
Amiodarone is the most efficacious medication for VT. However, it is important to recognize possible life-threatening complications of this medication, such as AIT, which itself can exacerbate VT.
Abstract 10990: The Prognostic Significance of Right Ventricular Dilation Assessed by Cardiac Magnetic Resonance Imaging in Heart Failure With Reduced Ejection Fraction
Authors: Malkawi Abdallah , Altibi Ahmed , Mansour Munthir , Schwitter Juerg , Guaricci Andrea , Masci Pier-Giorgio , De Cecco Carlo , Carrabba Nazario , Varga-Szemes Akos , Masi Ambra , Baggiano Andrea , Barison Andrea , lanzillo chiara , Martini Chiara , moro claudia , Andreini Daniele , Conte Edoardo , Rabbat Mark , Focardi Marta , Perazzolo Marra Martina , Lombardi Massimo , Dobrovie Monica , Gaibazzi Nicola , PEDROTTI PATRIZIA , Schoepf Joseph , Mushtaq Saima , Censi Stefano , Tat Emily , Bogaert Jan , Lozano Torres Jordi , Sverzellati Nicola , Marco Guglielmo , Gismondi Annalaura , Gravina Matteo , Presicci Cristina , De Lazzari Manuel , Palumbo Alessandro , Valentini Adele , Di Giovine Gabriella , Fusini Laura , Margonato Davide , Timpani Mauro , Nese Alberto , Pepi Mauro , Cicala Gloria , Muscogiuri Giuseppe , Lorenzoni Valentina , Pontone Gianluca , Al'Aref Subhi J ,   on behalf of DERIVATE study investigators
Published: June 2023

Background:
Quantitative volumetric assessment of the right ventricle (RV) can significantly enhance risk stratification in heart failure (HF), especially with the increasing availability of cardiac MRI (CMR). The prognostic value of RV dilation measured by RV end diastolic volume indexed to body surface area (RVEDVi) is not yet well established. In this analysis, we investigate the prognostic significance of RVEDVi measured by CMR in a stable HF cohort.

Methods:
We conducted a retrospective analysis on the DERIVATE registry, a large cohort of stable HF patients who underwent baseline CMR and echocardiography assessment. We used the cut-off value 90ml/m
2
as the upper limit of normal for CMR-derived RVEDVi. The primary outcome was all-cause mortality (ACM), while the secondary outcome was a composite of ACM and/or heart failure hospitalization (HFH). A Cox proportional hazard model was used to evaluate the association with outcomes.

Results:
2,447 patients with HF and reduced ejection fraction (HFrEF) were included, with a median follow-up time of 959 days (IQR: 560-1590). Mean LVEF was 34.0 ± 10.8, mean age was 59.8 ± 14.0 years and 42% were females. Mean RVEDVi was 75.0 ± 29.4 ml/m
2
and 23.2% had an RVEDVi >90 ml/m
2
. Elevated RVEDVi (>90 ml/m
2
) was significantly associated with an increased risk for ACM (aHR= 1.40, 95% CI [1.17-1.67]
p
=0.01) and the composite of ACM/HFH (aHR= 1.40, 95% CI [1.03-1.90]
p
= 0.03).

Conclusion:
In a large cohort of HFrEF undergoing baseline CMR, elevated RVEDVi was associated with an increased risk of ACM and ACM and/or HFH, independent of LV systolic function.
Abstract 10998: Pulmonary Artery Pulsatility Measured by Cardiac Magnetic Resonance Imaging in Over 42,000 Participants Reveals Novel Genetic Risk Loci
Authors: Johnson Adam L , Morales Manuel A , WOOSTER Luke T , Li Rebecca H , Boerboom Sophie L , Ostrom Katrina , Sigurslid Haakon , Jiang Wanlin , Tian Wenjie , Zeghibe Ana , Singh Kuldeep , Barnes Hanna J , Lino cardenas christian L , Lee Sujin , Yu Paul B , Miller Clint L , Nguyen Christopher T , Malhotra Rajeev
Published: June 2023

Introduction:
Pulmonary artery (PA) hemodynamics are important predictors of mortality. However, genetic mechanisms underlying increased PA stiffness in diseases such as pulmonary hypertension are poorly understood, and targeted therapies are limited. Evaluation of PA hemodynamics frequently requires invasive right heart catheterization, limiting large-scale studies. This study leveraged cardiac magnetic resonance (CMR) imaging to non-invasively determine and characterize PA pulsatility, an established measure of pulmonary vascular compliance.

Methods and Results:
A deep-learning neural network was implemented to determine PA pulsatility, defined as the relative cross-sectional area change from diastole to systole, in 42,774 UK Biobank participants (intraclass correlation 0.94-0.96 compared with human readers). The mean (SD) PA pulsatility was 0.36 (0.11), and pulsatility decreased by 0.035 for every decade increase in age. Reduction in pulsatility by 0.1 was associated with the presence of congestive heart failure (OR 1.55 [95% CI 1.37-⁠1.76]), chronic obstructive pulmonary disease (OR 1.41 [1.29-⁠1.53]), or diabetes (OR 1.18 [1.13-⁠1.23]), and PA pulsatility was associated with increased all-cause mortality (HR 1.13 [1.03-1.23]) after adjusting for age and sex and excluding those with CHF or COPD (Fig A-B). A genome-wide association study of 40,496 participants identified loci on chromosomes 2 (top SNP: rs6738973) and 10 (rs2077218) associated with PA pulsatility at genome-wide significance (
p
  <  5 х 10
–8
; Fig C). Integrative fine-mapping analyses identified
PKDCC
and
PLCE1
among likely effector genes.

Conclusions:
This is the first population-based epidemiologic and genomics study of PA pulsatility. Decreased PA pulsatility is associated with advanced age, increased rates of comorbidities, and higher mortality. The genes
PKDCC
and
PLCE1
are among likely effectors of PA pulsatility and warrant further functional investigation.
Abstract 11098: End-Organ Dysfunction Differs in Patients With Heart Failure-Related vs. Acute Myocardial Infarction-Related Cardiogenic Shock
Authors: Varshney Anubodh S , Berg David , Palazzolo Michael G , Bohula Erin A , Katz Jason N , Van Diepen Sean , Morrow David ,   CCCTN Investigators
Published: June 2023

Introduction:
Severity of end-organ dysfunction correlates with outcomes in acute myocardial infarction-related cardiogenic shock (AMI-CS). The epidemiology of end-organ dysfunction in heart failure-related cardiogenic shock (HF-CS) has not been well described.

Methods:
Cardiac intensive care unit (CICU) admissions with CS in the Critical Care Cardiology Trials Network Registry (2017-2021) were identified and categorized as AMI-CS and HF-CS (
de novo
or acute-on-chronic HF). Admissions for each CS sub-type were characterized as having respiratory, kidney, liver, and/or neurologic dysfunction using definitions adapted from the Sequential Organ Failure Assessment score (
Fig A
). Outcomes were assessed by burden of non-cardiac organ dysfunction: no end-organ dysfunction (NEOD), single system end-organ dysfunction (SEOD), or multi-system end-organ dysfunction (MEOD).

Results:
A total of 2,911 CS admissions from 35 CICUs were identified, most of which were for HF-CS (71%, N = 2,068). The proportions of patients with NEOD, SEOD, and MEOD were 25%, 36%, 39% for HF-CS vs. 16%, 35%, 49% for AMI-CS (p<0.01). NEOD, SEOD, and MEOD rates were 19%, 31%, and 49% for
de novo
HF-CS vs. 27%, 37%, and 36% for acute-on-chronic HF-CS (p<0.01). Predominant type of organ dysfunction differed among CS sub-types, with higher rates of respiratory dysfunction in AMI-CS and
de novo
HF-CS (p<0.01) and higher rates of hepatic dysfunction in both
de novo
and acute-on-chronic HF-CS (p<0.01;
Fig A
). In-hospital mortality was lower in acute-on-chronic HF-CS compared with
de novo
HF-CS or AMI-CS (25% vs. 32% vs. 38%; p<0.01), with a similar gradient of risk according to burden of non-cardiac organ dysfunction (p
int
= 0.64;
Fig B
).

Conclusions:
End-organ dysfunction pattern and burden differ among
de novo
HF-CS, acute-on-chronic HF-CS, and AMI-CS. Overall mortality is lowest in acute-on-chronic HF-CS, but mortality is similarly associated with burden of end-organ dysfunction among CS types.
Abstract 11125: Association of Interleukin-6 and Interleukin-18 With Global Cardiovascular Disease in Older Adults
Authors: Jia Xiaoming , Buckley Leo , Sun Caroline , Al Rifai Mahmoud , Yu Bing , NAMBI VIJAY , Virani Salim S , Selvin Elizabeth , Matsushita Kuni , Hoogeveen Ron C , Coresh Josef , Shah Amil M , Ballantyne Christie M
Published: June 2023

Introduction:
Increasing evidence suggest that inflammation plays an important role in chronic disease progression in the elderly, a process known as inflammaging. We assessed the associations of interleukin-6 (IL-6) and interleukin-18 (IL-18) with global cardiovascular disease (CVD), atrial fibrillation (AF) and death among older adults.

Methods:
Participants from Atherosclerosis Risk in Communities study visit 5 (2011-2013; mean age 75.4±5.1 years) with measurements of IL-6 and IL-18 were included (N=5672). Enzyme-linked immunosorbent assay was used to quantify IL-6 and IL-18. The associations of IL-6 and IL-18 (modeled continuously and categorically as tertiles) with coronary heart disease (CHD), ischemic stroke, heart failure (HF), global CVD (composite of CHD, stroke, and HF), AF, and all-cause death were assessed using Cox regression analyses.

Results:
Over a median follow-up of 7.2 years, 1235 global CVD events, 530 AF events and 1173 deaths occurred. Higher IL-6 and IL-18 levels were both associated with global CVD after adjustment for cardiovascular risk factors. The association between IL-6 and CVD remained significant after further adjustment for IL-18, while the association between IL-18 and CVD was no longer significant after adjustment for IL-6. IL-6 but not IL-18 was also associated with increased risk for CHD, HF, and AF after adjustments for cardiovascular risk factors and each other. Both IL-6 and IL-18 were associated with increased risk for all-cause death (Table). In categorical analysis, the top tertile of IL-6 was associated with increased risk for global CVD, AF and death using the lowest tertile as the reference group.

Conclusion:
Among older adults, both IL-6 and IL-18 were associated with global CVD and death. However, the association of IL-18 with CVD appears to be mediated by IL-6.