bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9006: Covid-19 Infection and Incident Myocarditis: A Population-Based Propensity Score-Adjusted Analysis
Authors: Priyadarshni Shivani , Baillargeon Jacques , Westra Jordan , Kuo Yong-Fang , Raji Mukaila
Published: April 2024

Introduction:
COVID-19-infection caused by Severe Acute Respiratory Syndrome Coronavirus -2—has protean manifestations ranging from asymptomatic infection to multi-organ failure and death. Cardiovascular complications from COVID -19 include myocarditis, acute myocardial infarction (AMI), heart failure (HF). These complications—captured clinically and by tests (troponins, 2-D ECHO, MRI)—can occur either by direct injury to the myo-pericardium or by an inflammatory response and cytokine storm. Population-level data is lacking on the relationship between COVID-19 and onset of Myocarditis, AMI, and HF. Therefore, we examined the incidence and correlations of Myocarditis, AMI, and HF after COVID-19 infection across the United States using a large nationwide database.

Hypothesis:
Infection with COVID-19 is associated with an increased risk of myocarditis.

Methods:
We used a retrospective cohort study using de-identified data from 35 health systems across the United States. Cohort groups were created using patients ≥18, who were admitted to hospitals for respiratory illness with COVID in 2020 and respiratory illness without COVID-19 for the years 2020 and 2019. Patients with prior cardiovascular events were excluded from the study. There were 103,187 patients with COVID; 77,242 patients with respiratory illness in 2020, and 114,908 patients with respiratory illness in 2019. The COVID group was matched to each of the respiratory illness groups by propensity score. Three main cardiovascular outcomes were studied: myocarditis, AMI, HF.

Results:
In the COVID-19 group, 79 patients had new-onset myocarditis compared to 29 patients in the non-COVID-19 control group (Odds ratio [OR] 2.73, CI 95%, 1.78-4.18). In the COVID-19 group, 1512 patients developed HF compared to 2,659 patients in the non-COVID-19 group, (OR 0.49, CI 95%, 0.46-0.52). 1125 patients in COVID-19 group had AMI compared to 1243 patients in non-COVID-19 group (OR 0.87, CI 95 %, 0.80-0.94).

Conclusions:
COVID-19 patients had 2 to 3 times the odds of incident myocarditis compared to non-COVID controls. Unexpected findings were the lower rates of HF diagnoses in the COVID -19 group, suggesting possible under testing (e.g., 2-D ECHO) and underdiagnosis in isolated COVID patients.
Abstract 9024: Molecular Mechanism of Chronic Beta3-Adrenergic Receptor Antagonist Caused Regression of Diabetic Cardiomyopathy in a Murine Model With Type 2 Diabetes
Authors: Cheng Heng , Cao Jing , Sun Xiaoqiang , Liu Yixi , Li Tiankai , Kitzman Dalane W , Zhao David , McClain Donald , Cheng Che Ping
Published: April 2024

Background:
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes (DM). As yet, no effective therapeutic strategies exist. Recently, we found that DM-induced LV dysfunction was prevented by chronic treatment with a β
3
-adrenergic receptor (AR) antagonist (β
3
ANT). However, the molecular mechanism is unclear. We hypothesized that reversal of DM-induced detrimental alterations on the expressions of cardiac SR Ca
2+
-ATPase (SERCA2a), β-ARs, nitric oxide synthase (NOS) by β
3
ANT may play a key role for its salutary role in DCM.

Methods:
The protein levels of myocyte β
1
- and β
3
- AR, SERCA2a, NOS and myocyte functional responses were determined in 3 groups (7/group) wild-type female mice over 14 weeks (W):
Type 2 DM
(
T2
), 14 W fed a high-fat diet (HFD), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days);
T2β

3

ANT
, T2 mice at 10 W received L-748,337, a selective β
3
ANT (10
-7
M/kg/day, mini-pump) for 4 W; and
Vehicle controls
(C).

Results:
Versus C, T2DM was induced in mice received HFD and low dose STZ with significantly elevated blood glucose (~340 to 380 mg/dl). Only T2 mice had significantly decreased protein levels of LV myocyte β
1
-AR (T2: 0.35 vs C: 0.49) and SERCA2a (0.19 vs 0.29), but increased β
3
-AR (0.25 vs 0.14) and iNOS (0.25 vs 0.15) without significant changes in eNOS (0.14 vs 0.13) and nNOS. These changes were followed by significantly reduced basal cell contraction (dL/dt
max
, 75.4 vs 133.7 μm/s), relaxation (dR/dt
max
, 59.6 vs 113.8 μ m/s) and [Ca
2+
]
iT
(0.16 vs 0.21). The isoproterenol (ISO, 10
-8
M)-stimulated increases in dL/dt
max
(38% vs 58%), dR/dt
max
(34% vs 55%) and [Ca
2+
]
iT
(19% vs 30%) were also significantly reduced. By contrary, versus C, T2β
3
ANT myocytes had similar protein levels of β
1
-AR (0.52), SERCA2a (0.75) and iNOS (0.36) with preserved normal basal cell contractility (127.8 μm/s), relaxation (109.4 μm/s) and [Ca
2+
]
iT
(0.21). ISO caused increases in dL/dt
max
(57%), dL/dt
max
(52%), and [Ca
2+
]
iT
(30%) were also closed to control values.

Conclusions:
Chronic β
3
ANT prevents DCM-caused downregulations of cardiac β
1
-ARs and SERCA2a, and normalized upregulations of iNOS and β
3
-AR, thus leading to the preservation of normal myocyte contractile function, [Ca
2+
]
iT
, and β-adrenergic reserve in a mouse model of T2DM.
Abstract 9043: Prognostic Significance and Interplay Between Heart Failure and Covid-19
Authors: Greene Stephen J , Lautsch Dominik , Yang Lingfeng , Tan Xi , Brady JoAnne
Published: April 2024

Introduction:
COVID-19 may negatively impact prognosis for patients with chronic HFrEF, and vice versa. However, large-scale data characterizing the interplay of COVID-19 and HFrEF on clinical outcomes are scarce.

Methods:
We examined the TriNetX health database from January 2020-September 2020 to conduct 2 analyses. Analysis A excluded patients with HFpEF and included patients with a positive inpatient or outpatient test for COVID-19, with a 3-way comparison of patients 1) without prior HF, 2) HFrEF without recent worsening HF event (WHFE) (i.e., no HF hospitalization or outpatient IV diuretic within prior 1 year), and 3) worsening HFrEF (i.e., HF hospitalization or outpatient IV diuretic within prior 1 year). Outcomes included mortality at 30 days and composite all-cause mortality or hospitalization following COVID-19 test. Analysis B included patients with HFrEF who underwent PCR testing for COVID-19, and compared patients with a positive versus negative test. Outcomes were mortality at 30 days and worsening HF (i.e., HF hospitalization or outpatient IV diuretic use).

Results:
In analysis A, 98,014 (99%) patients had no prior HF, 524 (0.5%) had HFrEF without WHFE, and 514 (0.5%) had worsening HFrEF. After adjustment for confounders, compared with patients without HF, worsening HFrEF was independently associated with excess mortality (p<0.01), whereas HFrEF without WHFE was not statistically significant (p=0.06)
(Table)
. In analysis B, 1,038 (7%) had a positive test for COVID-19 and 13,800 (93%) had only negative tests. After adjustment, testing positive for COVID-19 was independently associated with mortality and worsening HF (all p<0.01).

Conclusions:
In this US population of ambulatory and hospitalized patients, after accounting for confounders, worsening HFrEF was independently associated with excess mortality after COVID-19 infection. Among patients with HFrEF, COVID-19 infection was associated with higher risk of death and worsening HF events.
Abstract 9156: P-Wave Axis is an Independent Predictor of Mortality in Type II Diabetes Mellitus: The Diabetes Heart Study
Authors: Patil Pooja D , Singleton Matthew J , Saylor Georgia , Bowden Donald , Yeboah Joseph
Published: April 2024

Introduction:
Abnormal P-wave axis (PWA) has been associated with an increased risk of all-cause and cardiovascular mortality in various populations. However, the correlation of this prognostic indicator with mortality has not been systematically studied in patients with type II diabetes mellitus (T2DM) over a long-term period. The aim of this study was to investigate the association between abnormal PWA and all-cause mortality in participants from the Diabetes Heart Study (DHS).

Methods:
Out of the 1,443 participants in the DHS, 1,101 participants with T2DM and PWA data from electrocardiogram were included in the analysis. Kaplan-Meier (KM) and Cox proportional hazards models were used to analyze the association between PWA and mortality, adjusting for demographics and other potential confounding variables.

Results:
85 of the 1,101 participants (7.7%) had abnormal PWA. The mean age of all participants was 61.8 ± 8.9 years, with 45.7% of participants being male. Over a mean follow-up of 12.1 ± 4.4 years, a total of 504 deaths (45.8%) occurred. KM analysis showed that participants with abnormal PWA had a significantly higher rate of death than those with normal PWA (Log-Rank p<0.0001). Abnormal PWA was associated with increased risk of mortality (HR: 1.75, 95% CI: 1.31-2.29). After multivariable adjustment, the association remained significant (HR: 1.55, 95% CI: 1.14-2.06). Interaction analysis demonstrated a significant interaction between race and PWA group (p=0.03). Subgroup analysis showed increased risk of mortality with abnormal PWA in white participants, but no significant association between mortality and abnormal PWA in black participants (p=0.81).

Conclusions:
Abnormal PWA is independently associated with increased risk of mortality in a cohort of participants with T2DM. Further research on the association between race, PWA, and mortality risk is warranted. PWA may serve as an independent prognostic indicator of mortality risk in patients with T2DM.
Abstract 9172: Feasibility and Efficacy of Targeted Cardiac NF-kB Inhibition in Experimental Diastolic Dysfunction Using Drug-Delivery Technology: A Proof-of-Concept Study
Authors: Chade Alejandro R , Eirin Alfonso , Bidwell Gene L
Published: April 2024

Introduction:
Elastin-like polypeptides (ELP) are novel drug delivery vectors that can be fused to therapeutic agents and cell penetrating peptides (CPPs), slowing their plasma clearance and increasing uptake by target tissues. We developed a CPP-ELP fusion to a specific inhibitor of the p50 subunit of NF-kB (SynB1-ELP-p50i). We developed a swine model of chronic kidney disease (CKD) that also fosters hypertension, cardiac remodeling, and diastolic dysfunction, and observed that cardiac abnormalities associate with increased cardiac expression of NF-kB, a ubiquitous transcription factor that modulates cardiac inflammation, fibrosis, and vascular remodeling.

Hypothesis:
We aimed to define the feasibility and efficacy of intra-coronary (IC) SynB1-ELP-p50i administration to test whether a targeted inhibition of NF-kB can improve cardiac abnormalities in CKD.

Methods:
We first performed a biodistribution study (BDS) in 3 pigs, 4 hours after IC injection of fluorescently labeled SynB1-ELP-p50i (10 mg/kg). Then, CKD was induced in 6 pigs (bilateral renovascular disease and dyslipidemia), treated with a single IC SynB1-ELP-p50i or placebo at 6 weeks and observed for 8 more weeks. Cardiac morphology and function were quantified before/after treatment by echocardiography. After completion of the studies, pigs were euthanized and hearts excised for
ex vivo
studies.

Results:
Using IVIS technology, the BDS showed significant retention of SynB1-ELP-p50i in the heart. In the efficacy study, a single IC administration of IC SynB1-ELP-p50i reduced cardiac NF-kB expression, improved cardiac relaxation, and remodeling compared to untreated CKD (Figure).

Conclusions:
We show for the first time the feasibility of a targeted inhibition of cardiac NF-kB using ELP technology in a translational model of CKD and diastolic dysfunction. Our study may set the stage for a new therapeutic strategy using unique drug-delivery technology never tested before to protect the heart.
Abstract 9188: Sex Differences in Cardiovascular Risk and Guideline-Based Preventive Medication Use Among Sudden Death Victims
Authors: Keen Susan , Shartle Kaitlin , Simpson Ross J
Published: April 2024

Introduction:
Atherosclerotic cardiovascular disease (ASCVD) is associated with an increased risk of sudden death. Preventive medications are recommended by clinical practice guidelines for those with elevated ASCVD risk. Guidelines are often underutilized and use of preventive medications differs by sex.

Methods:
Out-of-hospital deaths of adults aged 18-64 were reported by emergency medical services in Wake County, North Carolina from 2013-2015 and underwent adjudication to identify sudden unexpected death cases. A cohort of 1,114 living controls was generated through random sampling from a central electronic health records repository and propensity scores matched to the sudden death victims based on sex and race. A 10-year ASCVD risk was calculated for all subjects with the requisite components and categorized as low (<7.5%), intermediate (7.5%-19.9%), and high (≥20%). Use of preventive medications, specifically aspirin and statin, was assessed. Logistic regression models were fitted to evaluate the association between 10-year ASCVD risk and sudden death both overall and by sex. Odds ratios for males and females were compared in a pairwise fashion using an adjusted Wald test.

Results:
The average 10-year ASCVD risk was higher among sudden death victims compared to living controls for both males (36.4 ± 22.2 vs. 16.3 ± 16.0, p-value <0.001) and females (20.6 ± 17.9 vs. 7.1 ± 8.4, p-value <0.001). Among intermediate or high 10-year ASCVD risk sudden death victims and controls, aspirin and statin use were low (13-21%). Among those with intermediate or high ASCVD risk, male sudden death victims were less likely than living controls to be prescribed aspirin (p-value 0.007). Comparing sudden death victims to living controls, there was no difference in statin use among males or in aspirin or statin use among females. There was no significant difference in the strength of association between 10-year ASCVD risk categories and sudden death by sex.

Conclusions:
Although the average 10-year ASCVD risk of sudden death victims is higher than living controls both overall and by sex, the use of aspirin and statin was low and did not differ significantly between victims and controls. Improvements are needed to increase the use of guideline-based preventive medications.
Abstract 9189: Diagnostic Validity of Genetic Testing for Hypertrophic Cardiomyopathy - A Systematic Review and Meta-Analysis
Authors: Kelly Melissa A , Cirino Allison , Hansen Brittany P , Harris Stephanie , Murad Andrea M , Natoli Jaime , Malinowski Jennifer , Christian Susan
Published: April 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) is a routine indication for genetic testing. However, our understanding of the impact of genetic testing on clinical outcomes is limited. This study systematically summarizes the diagnostic validity of genetic testing for patients with HCM and at-risk relatives.

Methods:
PubMed (MEDLINE), Embase, CINAHL, and Cochrane Central Library were queried using keywords pertaining to HCM, genetic counseling, and genetic testing. The initial search was conducted on July 7, 2017 and updated on March 2, 2020. Abstracts and full-texts were reviewed for original research studies where genetic testing was performed in ≥10 patients with HCM, or their relatives. A total of 132 articles met inclusion criteria. Review was performed according to PRISMA guidelines. Relevant data were extracted and validated by a second reviewer. Risk of bias and quality were assessed using the Cochrane Risk of Bias or Newcastle-Ottawa tools in duplicate. Disagreements were resolved through discussion or a third reviewer. Pooled analyses were performed using random-effects models.

Results:
Detection rate was significantly higher in pediatric cohorts compared with adults (56% vs. 42%; p=0.01) and in adults with a family history compared to sporadic cases (59% vs. 33%; p=0.005). Use of current variant interpretation standards from the American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) significantly lowered adult detection rate from 42% to 33% (p=0.0001). The mean difference in age-of-onset in adults was significantly younger for genotype-positive versus genotype-negative cohorts (8.3 years; p<0.0001),
MYH7
versus
MYBPC3
(8.2 years; p<0.0001), and individuals with multiple versus single variants (7.0 years; p<0.0002). Disease penetrance in adult cohorts was 62%, but differed significantly depending on if probands were included or excluded (73% vs. 55%; p=0.003).

Conclusions:
This meta-analysis is the largest, if not the first, to refine and quantify historical understandings of detection rate, genotype-phenotype associations, and disease penetrance for HCM, therefore allowing everyday clinical questions to be answered with more confidence
Abstract 9296: Impact of the Covid Pandemic on Aortic Valve Replacement and Coronary Artery Bypass Graft Surgical Outcomes
Authors: Fox Daniel , Joynt Maddox Karen
Published: April 2024

Introduction:
Patients with coronary artery disease or cardiac valvular disease in need of cardiac surgery are typically high-risk, and may have been impacted either by delays in seeking care for their underlying cardiac condition, or by disruptions in hospital care itself.

Hypothesis:
we examined changes in volume, complexity, and outcomes for aortic valve replacement (AVR) and coronary artery bypass graft (CABG) patients at a large midwestern teaching hospital during the COVID pandemic.

Methods:
We used diagnosis and procedure codes to identify all patients undergoing AVR or CABG, without a documented COVID19 diagnosis, at Barnes-Jewish Hospital between 1/2018 and 9/2020. We used multivariable regression models to examine the association between the COVID time period and outcomes, controlling for age, sex, and medical comorbidities.

Results:
For the AVR and CABG cohort, we saw no statistically significant differences in weekly volume, age, gender, payor, or race (Table 1).In the AVR cohort, patients were more complex during COVID, and risk-adjusted in-hospital mortality was higher during COVID compared to pre-COVID. For the CABG cohort, we found numeric increases but no statistically significant differences in patient complexity, nor in risk-adjusted mortality (Figure 1).

Conclusions:
We found higher in-hospital mortality among patients undergoing AVR during COVID, a pattern that was not statistically significant in CABG. These findings suggest that outreach to patients is critical to ascertain which patients require necessary surgical care during future pandemic waves or other disruptions to usual care.
Abstract 9323: Molecular Defects Are Not Associated With Occurrence of Cardiovascular Events in Older Individuals With Familial Hypercholesterolemia on Lipid Lowering Therapy
Authors: Coutinho Elaine , Miname Marcio H , Rocha Viviane Z , Bittencourt Marcio S , Jannes CInthia , Pereira Alexandre , Krieger Jose , Santos Raul D
Published: April 2024

Introduction:
Familial hypercholesterolemia (FH) is a genetic disorder associated with early onset atherosclerotic cardiovascular disease (ASCVD). However, lipid lowering therapies (LLT) may change FH natural history. There is scant data about elderly (≥60 years) with FH.

Hypothesis:
FH molecular defect may not influence on ASCVD risk after LLT in older individuals.

Methods:
Older hypercholesterolemic individuals were divided into 4 groups (2X2) according to the presence (FH +) or not of genetic variants (FH-) and previous or not clinical ASCVD (ASCVD+ and ASCVD-). Association of biomarkers with ASCVD onset was tested using Cox models.

Results:
From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71)] years, 28.9% men, 42.7% FH+, LDL-C on LLT 144 (109; 200) mg/dL, median LLT duration 9 (5;16) years. Overall ASCVD was present in 32.1%, and 62.1% and 34.5% had ASCVD of early onset in FH+ and FH- respectively. FH-/ASCVD+ (n=161), FH+/ASCVD- (n=95), FH-/ASCVD+ (n=55) and FH+/ASCVD+(n=66) were followed by 4.8(7;3) years and 51 new ASCVD events (2.8/100 patients/year) occurred. No differences were seen regarding age, hypertension, body mass index, current use, duration, and intensity of LLT and LDL-C at the last follow-up visit. In univariate analysis there was an association of male gender (p = 0.002), presence of genetic variants (p = 0.006), diabetes (p = 0.006), smoking (p = 0.028) and previous ASCVD (p = 0.000) with new ASCVD event. There was no association of LLT and current or previous lipid profile, except with HDL-C at diagnosis (p=0.014), with ASCVD event. Table 1 shows that after multivariate analysis the genetic defect was not associated with occurrence of ASCVD events.

Conclusion:
Although FH is associated with a higher risk of early ASCVD even when compared to other hypercholesterolemics, in older individuals after LLT the presence of genetic defects was not associated with the occurrence of new events.
Abstract 9338: In-hospital Complications During 35747 Permanent Pacemaker Implantations from 2009-2018: A Statewide Australian Cohort Study
Authors: Vijayarajan Vijayatubini , Ng Austin Chin Chwan , Brieger David , Chow Vincent , Kritharides Leonard
Published: April 2024

Background:
Permanent pacemaker implantation (PPI) is standard of care for significant bradyarrhythmia since the early 1960’s. Understanding its utilisation and projection in our ageing populations has important implications on medical resource utilisation. This study reports the rates of PPI in the state of New South Wales (NSW), Australia from 2009-2018.

Hypothesis:
We hypothesized PPI in patients ≥80yrs has increased faster than in <80yrs over past decade.

Methods:
We examined the prevalence of PPI from Jan 2009 to Dec 2018 by extracting administrative details of all permanent pacemakers implanted statewide, including patient’s characteristics and in-hospital complications using the NSW Centre-for-Health-Record-Linkage datasets. All analysis was stratified by age <80yrs vs ≥80yrs old.

Results:
A total of 35747 admissions involved PPI (60% males) during the study period. The mean ±SD implantation rate and age was 3574±311 PPI per annum and 78±10yrs respectively. 18187 (50.9%) of PPI were in patients ≥80yrs. The mean annual rate of PPI was 593.4±57.6 per 100000 persons for ≥80yrs, compared to 24.5±2.1 per 100000 persons in <80yrs (p=0.0001). The overall mean rate of increase in PPI from 2009-2018 for ≥80yrs old was 2.6±3.7% compared to 1.7±3.2% per annum in <80yrs (p=0.001). The median (interquartile range [IQR]) length of stay (LOS) in patients ≥80yrs requiring emergency PPI was 8 (5-14) days, compared to 1 (1-3) days in those who had an elective PPI procedure, p<0.05. For patients <80yrs old, the median (IQR) LOS was 7 (4-12) days compared to 1 (1- 2) days, p<0.05 respectively. Overall, complications of pacemaker implantation excluding death was 8%. Although overall in-hospital mortality was low, it was higher for patients ≥80yrs compared to the <80yrs group (0.9% vs 0.6%; p<0.001). Overall complication rates declined only in last two years of the study period, with no significant change for in hospital death.

Conclusion:
Overall PPI increased between 2009-2018, with the increase greatest in patients ≥80yrs. Overall complication rates remained elevated, with in-hospital mortality higher in the older group. Future studies should examine strategies that reduce in-hospital complications during pacemaker implantations.
Abstract 9355: Home Monitoring to Detect Emergent Anti-Ro/SSA Antibody Mediated Fetal Av Block: Preliminary Results of the STOP BLOQ Study
Authors: Drewes Bailey M , Phoon Colin K , Sinkoveskaya Elena S , Howley Lisa W , Acherman Ruben J , Makhoul Majd , Pinto Nelangi M , Masson Mala , Benson D W , Abuhamad Alfred , Buyon Jill P , Cuneo Bettina F
Published: April 2024

Introduction:
Fetal complete AV block (CAVB), complicates 2% of anti-Ro antibody positive pregnancies and carries substantial perinatal morbidity and mortality. Anti-inflammatory treatment of 1° and 2° (emergent) AVB may prevent progression to CAVB, yet the optimal surveillance strategy to detect emergent CAVB is unknown.

Methods:
We examined participants in a multicenter, open label clinical trial of pregnancies risk stratified by anti-Ro antibodies into high (≥1000 IU) or low (<1000 IU) titers. Low titer mothers were followed by echocardiograms or routine OB care; high titer mothers underwent 3x/day fetal heart rate monitoring (FHRM) and weekly or biweekly fetal echocardiograms from 17-26 weeks. If mothers suspected abnormal FHRM, they texted fetal heart sounds to cardiologist, who assessed FHRM and reassured or referred for emergency fetal echocardiogram (performed in < 6 hours). Postnatal electrocardiograms (ECG) were evaluated.

Results:
Sixty-five subjects from 7 centers were recruited and 60 (92%) enrolled at 14 (5-19) weeks. There were 24 (40%) low titer and 36 (60%) high titer mothers. High titer mothers underwent FHRM; 92% completed FHRM and 100% completed surveillance echocardiograms. Of 3,360 FHRM recordings, mothers texted 39 (1%) recordings of concern; cardiologist deemed 2/39 (5%) as abnormal and emergency echocardiograms revealed atrial ectopy. No fetus developed emergent or CAVB. Postnatal ECGs demonstrated normal AV conduction in all neonates: 2 miscarried at <12 weeks and 48 are in utero.

Conclusion:
These data support FHRM in the surveillance of anti-Ro antibody positive pregnancies because of high enrollment, feasibility, and accuracy in arrhythmia detection.
Abstract 9374: The Attenuation of Blood Pressure Lability Assessed by Frequency Analysis of Very Short-Term Continuous Blood Pressure Recording Reflects the Hemodynamic Aggravation in Heart Failure Patients with Reduced Ejection Fraction
Authors: Suematsu Yasunori , Saku Keita , Miyazaki Midori , Yano Yuiko , Arimura Tadaaki , Fujimi Kanta , Miura Shin-ichiro
Published: April 2024

Introduction:
The lower blood pressure variability (BPV) assessed by 24-hour ambulatory bloop pressure (BP) monitoring predicts cardiac events in heart failure with reduced ejection fraction (HFrEF) patients. However, the trends of BPV assessed by short-term continuous BP recording in HFrEF patients remains unknown.

Hypothesis:
We recently reported a novel method of BPV analysis which is focused on the power spectral density (PSD) of 30-min continuous BP recording. In the PSD, we defined the integrated area of PSD from 0.01Hz to 0.1Hz as an index of short-term BPV (BP lability index: BLI) (Figure 1). Since the worsening of cardiac function decreases the dynamic variability of BP, we hypothesized that reduced cardiac function lowers BLI. In this study, we investigated how the worsening of cardiac function alters BLI.

Methods:
We compared 33 HFrEF patients with 15 hypertensive (HT) patients as a normal cardiac function. We assessed baseline characteristics, the value of brain natriuretic peptide (BNP), echocardiography and 30-min continuous BP in those patients. BP time series in each subject was converted to PSD by the Fourier transform.

Results:
Compared to HT, HFrEF patients showed lower left ventricular ejection fraction (LVEF) (33.8±11.8 vs. 68.9±6.8 %, p<0.001) and higher E/e’ (17.5±10.8 vs. 10.5±2.7, p=0.002), indicating the hemodynamic aggravation. In continuous BP, HFrEF reduced both averaged systolic BP (122.0±18.1 vs. 137.9±19.7 mmHg, p=0.006) and pulse pressure (50.1±13.9 vs. 59.2±14.9 mmHg, p=0.037). BLI was significantly lower in HFrEF patients than that in HT (2.07±0.98 vs. 2.64±0.95, p=0.010]. Interestingly, the patients with reduced LVEF and high E/e’ showed lower BLI (Figure 2). Furthermore, BLI negatively associated with BNP (r=-0.38, p=0.012) (Figure 3).

Conclusions:
BLI was lower in HFrEF patients than that in HT patients with normal cardiac function. BLI has a potential to develop a novel marker of hemodynamic assessment in HFrEF patients.
Abstract 9384: Evolocumab, a Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitor, Reduces Doxorubicin, Trastuzumab and Nivolumab Induced Cardiotoxicity Through Mtorc1 and Myd88 Related Pathways
Authors: Maurea Nicola , Iovine Martina , Buccolo Simona , Paccone Andrea , Cerrone Francesca , Quagliariello Vincenzo
Published: April 2024

Introduction:
The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Recent studies indicates the crucial involvement of PCSK9 in regulation of cardiac cell metabolism and survival. Doxorubicin and trastuzumab-induced cardiotoxicity still remains a clinically relevant problem in cancer patients. Patients treated with nivolumab experienced myocarditis, arrhythmia and heart failure; therefore finding new cardioprotective strategies in this patient cohort is a very important clinical need.

Hypothesis:
Considering the expression of PCSK9 in heart tissue and cardiomyocytes, we aimed to study the direct effects of evolocumab in cardiomyocytes during exposure to doxorubicin, trastuzumab and nivolumab

Methods:
Human fetal cardiomyocytes were exposed to subclinical concentration of doxorubicin, trastuzumab (both at 100 nM), nivolumab (200 nM) alone or in combination with evolocumab (50 nM) for 48h. After the incubation period, we performed the following analysis: cell viability, apoptosis and necrosis, lipid peroxidation and intracellular Ca
2+
concentration. Through ELISA method, we studied the expression of NLRP3 inflammasome, MyD88, mTORC1, nuclear NF-κB. Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed.

Results:
Evolocumab co-incubated with anticancer drugs increased significantly the cell viability from 38 to 58 % compared to doxorubicin, trasuzumab and nivolumab groups (p<0,01 for all). Evolocumab downregulates MyD88, mTORC-1 and nuclear NF-kB with a significant reduction in IL-1α, IL-1β, IL17-α, G-CSF and GM-CSF (p<0.05 vs doxorubicin, trasuzumab and nivolumab groups).

Conclusions:
The PCSK9 inhibitor evolocumab exerts cytoprotective effects on cardiomyocytes during exposure to doxorubicin, trastuzumab and anti PD-1 antibody nivolumab. This study open to new preclinical trials aimed to decrease cardiotoxicity during anticancer therapies.
Abstract 9819: Real World Data: Off-Label Metformin in Patients with Prediabetes is Associated with Improved Cardiovascular Outcomes
Authors: Murillo Jaime E , McNeil Chace , Van Nest Kathryn , Schaeffer Jamie , Polingo Lynn , Adjei Solomon , Shapiro Victoria , Wiegand Ben , Deneen Vojta
Published: April 2024

Background:
Metformin is not FDA-approved for prediabetes but it is being prescribed off-label for this condition. Per the American Diabetes Association (ADA), metformin “should be considered” for prediabetes patients with a BMI
>
35. Prediabetes is associated with a higher risk of cardiovascular disease (CVD). We report on real-world, off-label use of metformin and its association with lower incidence of CVD in a large population with prediabetes, by age, BMI, and race.

Methods:
This analysis used insurance claims linked to electronic health records from Jan 2016 to Sept 2020. Patients in the metformin cohort had
>
180-day supply:
>
90 days pre- and
>
90 days post diagnosis of prediabetes. All had continuous enrollment for
>
24 months. We excluded age <25; FDA-approved metformin indications; type 1 DM; CVD; CKD; or gestational diabetes. Inclusion criteria: Prediabetes ICD-10 code R73, or HbA1c 5.7-6.4, or fasting glucose 100-125 mg/dL or OGTT 140-199 mg/dL.

Results:
Of 149,654 patients with prediabetes, 8,624 (5.8%) were prescribed metformin. Table 1 describes metformin and non-metformin patients.

At a 2.8-year mean follow-up, 24% of prediabetes patients developed CVD. Table 2 describes metformin use and CVD outcomes by BMI, gender, race, and age. As a whole and by gender, a BMI
>
35 was associated with lower CVD. A similar effect was seen for AA
>
65 with a BMI
>
35

Conclusion:
Patients with BMI
>
35 showed an association between metformin use and lower incidence of CVD, including African Americans older than age 65. The data suggest that morbidly obese patients with prediabetes may benefit from the use of metformin as recommended by the ADA.
Abstract 9853: Covid-19 Myocarditis: Quantitative Analysis of the Inflammatory Infiltrate
Authors: Vander Heide Richard S , Fox Sharon E
Published: April 2024

Introduction:
COVID-19 has a significant effect upon the cardiovascular system including small amounts of myocyte death in some patients resulting in elevated troponin levels. While a number of different cardiovascular histopathologies have been described at post-mortem examination, the incidence of typical viral myocarditis in COVID-19 positive patients appears very low.

Hypothesis:
We hypothesized that COVID-19 causes a different type of inflammatory cell response that although different, may still cause significant negative effects on the cardiovascular system.

Methods:
Using immunoperoxidase staining, we characterized and quantified the number of CD3
+
, CD4
+
, CD8
+
, CD68
+
staining cells in 10 COVID-19 hearts, 10 hearts matched for age and underlying comorbidities, and 5 hearts with autopsy proven typical inflammatory myocarditis.

Results:
The results demonstrate a skewed distribution of the number of CD68+ cells in COVID-19 hearts, with upper quantiles showing a significant increase as compared to both matched control hearts, and those with myocarditis. In contrast, hearts from typical inflammatory myocarditis contained increased numbers of CD4+, and CD8+ cells compared to both COVID-19 and control cohorts. .

Conclusions:
In conclusion, the presence of an increased number of CD68+ cells suggests that COVID-19 may incite a form of myocarditis different from typical viral myocarditis, and associated with diffusely infiltrative cells of monocytes/macrophage lineage.
Abstract 9861: Establishing Normal Pediatric Aortic Valve Cusp Effective Height Utilizing the Pediatric Heart Network Normal Echo Z Score Project Echocardiograms
Authors: Goot Ben H , Kim Michael , Kuhn Evelyn , Altmann Karen , Camarda joseph , Chowdhury Shahryar M , Colan Steven D , Dragulescu Andreea , Goldberg David , Lopez Leo , Parra David , Patel Jyoti K , Pignatelli Ricardo H , Prakash Ashwin , Sachdeva Ritu , Soriano Brian , Spurney Christopher , Stylianou Mario , Thorsson Thor , Tretter Justin , Truong Dongngan , Frommelt Peter C
Published: April 2024

Introduction:
Standard echocardiographic dimensions provide little geometric insight into aortic valve (AV) function. The height difference between cusp insertion and free edge, known as AV cusp effective height (eH), can be assessed from the parasternal long axis view and is a surrogate measure of leaflet geometry. This is useful data when planning valve repair although normal values and methods of indexing eH have not been established in pediatric patients. Images from the Pediatric Heart Network (PHN) Normal Echocardiogram Database were analyzed to establish normal pediatric eH ranges and to assess relationship to typical AV and aortic root measures, age, and body size.

Methods:
AV eH and annulus diameter were retrospectively measured from 600 PHN echocardiograms divided into equal sized groups based on categories of age, sex, and race proportions in the primary study. Subset size was determined utilizing similar methods and presumed margin of error to primary study. Normal ranges were calculated and eH was compared to PHN AV annulus and aortic root dimensions, age groups, and BSA using Pearson correlation. Interobserver and intraobserver reliability was assessed. Regression equations were created using BSA and/or annulus diameter as the independent variables.

Results:
AV eH increases predictably with age in children (Fig 1). It correlates strongly with aortic dimensions (all r>0.82) and indexes incorporating BSA
0.5
(r=0.85). It is reproducible, with good interobserver (ICC=0.66, 0.11-0.85) and excellent intraobserver (ICC=0.82, 0.74-0.88) reliability. Regression equation created is eH=0.7+5.74* BSA
0.5
.

Conclusions:
Normal eH correlates well with age, standard aortic dimensions, and BSA
0.5
in healthy children and regression equations can be used to predict mean eH values in this population. Understanding these relationships will help in evaluating patient-specific valvular morphology when developing a surgical repair strategy.
Abstract 9917: Stroke Survivors with Asthma Have Worse Cardiovascular Outcomes
Authors: Zinonos Stavros , Vakil Deep , Wang Wenting , Kostis William J , Cabrera Javier , Kostis John B ,   for the Myocardial Infarction Data Acquisition System Study Group
Published: April 2024

Introduction:
Studies have shown that asthmatics have higher risk for cardiovascular (CV) disease and all-cause mortality than non-asthmatics. However, only a few studies have examined the role asthma has on CV outcomes of stroke survivors.

Hypothesis:
Stroke survivors with asthma have higher risk of CV outcomes (1- and 5-year all-cause mortality, 1- and 5-year admission for stroke recurrence, first occurrence of MI, or HF) than matched stroke survivors without asthma.

Methods:
A total of 271,260 patients, 18-years-old and older, with index stroke and without a history of HF, MI, or COPD from January 1, 1995 to December 31, 2015 were identified in the Myocardial Infarction Data Acquisition System, a database of all admissions to non-federal hospitals in New Jersey. A matched analysis was performed by separating the cohort into asthmatics (n=11,702) and non-asthmatics (n=34,950) and matched 1 asthmatic up to 3 non-asthmatics. Data was analyzed by matching patient and clinical characteristics. The association of asthma with each of the above outcomes was assessed using logistic regression, log-rank test, and Cox models.

Results:
There was no difference in 1-and 5-year all-cause mortality (p=0.102 and p=0.488, respectively). Patients with asthma were more likely to be readmitted for stroke within 1 year (hazard ratio (HR)= 1.08, 95% CI 1.00-1.16, p=0.041) and had first admission for HF at 1 year (HR 1.38, 95% CI 1.09-1.73, p=0.006) compared to matched controls. Also, they were more likely to be readmitted for stroke within 5 years (HR 1.08, 95% CI 1.02-1.15, p=0.007) and to be admitted for first HF within 5 years (HR 1.27, 95% CI 1.12-1.44, p<0.001) (Figure). There were no significant differences in 1-year and 5-year first MI admissions.

Conclusion:
Stroke survivors with asthma have higher risk for stroke readmission and first HF admission compared to matched controls. Randomized studies are needed to confirm these findings and stimulate focused efforts to mitigate this risk.
Abstract 9950: Right Ventricular Hemodynamic Forces: Linking Pulmonary Insufficiency to Wall Motion in Repaired Tetralogy of Fallot Patients
Authors: Loke Yue-hin , Capuano Francesco , Kollar Sarah , Cibis Merih , Kitslaar Pieter , Balaras Elias , Reiber Johan , Pedrizzetti Gianni , Olivieri Laura
Published: April 2024

Introduction:
Patients with repaired Tetralogy of Fallot (rTOF) will develop right ventricle (RV) dysfunction from chronic pulmonary insufficiency (PI). Cardiac magnetic resonance (CMR) biomarkers informs timing of pulmonary valve replacement (PVR), but do not clarify the direct impact of PI on myocardial biomechanics. 4D flow studies have shown that RV hemodynamic forces (HDF) are altered in rTOF. In this study, we derived HDF in rTOF, exclusively using RV wall motion from conventional cine.

Methods:
This was a retrospective study using CMR of rTOF patients who had no PVR at time of imaging. Feature-tracking (QStrain, Medis) was used to capture RV wall motion from cine imaging. A novel diffeomorphic mapping technique was used to calculate 3D RV kinematic models (Figure 1A) and global HDF vector generated throughout the cardiac cycle. The RVOT-to-Diaphragm HDF vector was isolated for analysis. Global longitudinal strain, QRS duration and RV size/function were collected. Repeat analysis was performed on subgroup of rTOF who had subsequent PVR and follow-up CMR.

Results:
44 rTOF studies (21±11 years) were included with regurgitant fraction (PR%) 33±15%, RV ejection fraction 50±5%, and RV end-diastolic volume 144±37 mL/m
2
. PR% correlated with RVOT-to-Diaphragm HDF vector in diastole (Figure 1B). Higher diastolic:systolic HDF ratio correlated with lower RV ejection fraction (R = -0.31, p = 0.04), lower global longitudinal strain (R = -0.38, p = 0.009), and longer QRS duration (R = 0.44, p = 0.004). 9 rTOF patients had follow-up CMR after PVR and demonstrated decrease in RVOT-to-Diaphragm HDF (Figure 1C).

Conclusions:
PI in rTOF patients is correlated to diastolic HDF exerted along the direction of the RVOT. Diastolic HDF correlates with RV dysfunction in rTOF patients, and as a global parameter can be captured by RV wall motion without the need to analyze 4D flow details. HDF is a potential biomarker that may provide early detection of RV dysfunction and inform PVR timing.
Abstract 9976: New Risk Factors for Improved Identification of Coronary Artery Disease Risk in Type 2 Diabetes by Substituting Paraoxonase 1 Activity for HDL Cholesterol in Atherogenic Ratios
Authors: Mahrooz Abdolkarim , Alizadeh Ahad , Khosravi-asrami Omeh farveh , Mohmmadi Neda , Bahar Adele , Mohmmadi Neda
Published: April 2024

Introduction:
HDL cholesterol (HDL-C) may not always represent the HDL function. This study was conducted to help predict the risk of coronary artery disease (CAD) in patients with type 2 diabetes (T2D) based on substituting paraoxonase 1 (PON1) as an important enzyme in HDL function for that of HDL-C in the atherogenic ratios LDL-C/HDL-C and log (TG/HDL-C).

Methods:
A total of 274 subjects undergoing diagnostic coronary angiography in this study; 92 without significant CAD and 182 with severe CAD. The hydrolysis rate of phenylacetate as a PON1 substrate was spectrophotometrically measured in kinetic mode. The area under the ROC curve (AUC) was calculated to quantify the overall discriminative capacity of the variables.

Results:
ROC analyses showed that LDL-C/PON1 (AUC=0.66, p=0.02) and log (TG/PON1) (AUC=0.65, p=0.019) had higher predictive powers compared with LDL-C/HDL-C (AUC=0.55, p=0.221) and log (TG/HDL-C) (AUC=0.57, p=0.121) for CAD characterization in T2D patients. Also, AUCs of LDL-C/PON1 (AUC=0.74, p=0.014) and log (TG/PON1) (AUC=0.67, p=0.057) were higher than those of LDL-C/HDL-C (AUC=0.51, p=0.469) and log (TG/HDL-C) (AUC=0.53, p=0.364) for predicting CAD in T2D patients with HbA1c ≥7%. The multiple regression analysis with adjustments for gender, age, BMI, duration of T2D, metformin and statin therapy indicated that LDL-C/PON1 [adjusted OR=1.1 (0.99,1.23), p=0.085] and log (TG/PON1) [adjusted OR=3.76 (0.94,14.89), p=0.058] were independently predictors of CAD in T2D patients.

Conclusions:
New cardiometabolic biomarkers using PON1 provide an incremental predictive value compared with those using HDL-C in identifying subjects at increased risk for CAD among patients with T2D and poor glycemic control. This study sought to exploit the lipoprotein-related biomarkers of CAD from a more effective perspective in T2D. Our findings may help develop clinically cost-effective and functional laboratory measurements to evaluate HDL function.
Abstract 9988: Racial/Ethnic Disparities in the Patients Undergoing Heart Transplantation: Insights from National Inpatient Sample 2016-2018
Authors: Minhas Abdul , Qavi Ahmed H , NAZIR SALIK , Khan Muhammmad , Hasan Hibaa , Fudim Marat , Nasir Khurram
Published: April 2024

Background:
There is a paucity of data on in-hospital outcomes of Heart Transplant (HT) recipients among different races. This study aimed to evaluate the impact of race on the clinical outcomes in the patients undergoing HT.

Methods:
We conducted a retrospective analysis of adult hospitalizations from the National Inpatient Sample (NIS) between 2016 and 2018. ICD codes were used to identify those who underwent HT. Prevalence estimates were weighted using NIS-provided discharge-level weights to reflect national estimates. Weighted multivariable logistic regression was used to assess the association of race and various clinical outcomes in those who underwent HT. Caucasians were kept as the reference category. These models were adjusted for several patient-level and hospital-level characteristics.

Results:
Among 7945 HT hospitalizations, 4835 (43.2%) were Caucasian, 1730 (41.7%) were African American, 814 (10.1%) were Hispanics and 565 (10.1%) were Others. After adjustment of variables, there was no significant difference in all-cause mortality, cardiac arrest, invasive mechanical ventilation, use of pressors, tracheostomy, gastrostomy, vascular complications, bleeding requiring transfusion, stroke or acute kidney injury in African-Americans, Hispanics and others when compared to Caucasians (Table 2).

Conclusions:
We did not find a significant difference in various hospital outcomes of HT recipients among different races.
Role of the prefrontal cortex in musical and verbal short-term memory: A functional near-infrared spectroscopy study
Authors: Ginzburg Jérémie , Cheylus Anne , Collard Elise , Ferreri Laura , Tillmann Barbara , Moulin Annie , Caclin Anne
Published: April 2024

Auditory short-term memory (STM) is a key process in auditory cognition, with evidence for partly distinct networks subtending musical and verbal STM. The delayed matching-to-sample task (DMST) paradigm has been found suitable for comparing musical and verbal STM and for manipulating memory load. In this study, musical and verbal DMSTs were investigated with measures of activity in frontal areas with functional near-infrared spectroscopy (fNIRS): Experiment 1 compared musical and verbal DMSTs with a low-level perception task (that does not entail encoding, retention, or retrieval of information), to identify frontal regions involved in memory processes. Experiment 2 manipulated memory load for musical and verbal materials to uncover frontal brain regions showing parametric changes in activity with load and their potential differences between musical and verbal materials. A FIR model was used to deconvolute fNIRS signals across successive trials without making assumptions with respect to the shape of the hemodynamic response in a DMST. Results revealed the involvement of the dorsolateral prefrontal cortex (dlPFC) and inferior frontal gyri (IFG), but not of the superior frontal gyri (SFG) in both experiments, in keeping with previously reported neuroimaging data (including fMRI). Experiment 2 demonstrated a parametric variation of activity with memory load in bilateral IFGs during the maintenance period, with opposite directions for musical and verbal materials. Activity in the IFGs increased with memory load for verbal sound sequences, in keeping with previous results with n-back tasks. The decreased activity with memory load observed with musical sequences is discussed in relation to previous research on auditory STM rehearsal strategies. This study highlights fNIRS as a promising tool for investigating musical and verbal STM not only for typical populations, but also for populations with developmental language disorders associated with functional alterations in auditory STM.