bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13947: Racial Differences in Peripheral Microvasculature's Association With Mild Cognitive Impairment
Authors: Gold Matthew E , Rogers Steven C , Kulshreshtha Ambar , Chen Yuxuan , Cheng Michael , Gold Daniel , Vatsa Nishant , Jain Vardhmaan , jain vardhmaan , Desai Shivang , Ko Yi-An , Moazzami Kasra , Thomas Tiffany , Okafor Maureen , Lah James , Goldstein Felicia C , Quyyumi Arshed A , Hajjar Ihab
Published: December 2023

Introduction:
Cardiovascular disease (CVD) and Alzheimer’s Dementia (AD) share numerous risk factors, with vascular dysfunction a common underlying mechanism. Individuals with mild cognitive impairment (MCI) have a high likelihood of developing AD in their lifetime. The link between microvascular dysfunction (MVD) and AD has yet to be fully established.

Hypothesis:
We examined the contribution of MVD to MCI with the hypothesis that Black Americans, who have a higher prevalence of MVD, will have higher rates of MCI.

Methods:
Participants >50 years with MCI or with normal cognition (NC) were enrolled for neuropsychological and microvascular function testing using peripheral arterial tonometry. Microvascular function was measured as the reactive hyperemia index (RHI) and calculated as the ratio of the post- to pre-occlusion pulse volume in the fingertip (EndoPAT). Multivariate analyses, adjusting for demographic and CVD risk factors associated with MCI, evaluated the relationship between RHI and MCI in Black and White participants. Causal mediation analysis, using the Monte Carlo approach, was performed to investigate whether the effect of RHI on MCI was mediated through plausible mediators, including risk factors.

Results:
Of 152 participants (NC=104, MCI=48), 41.4% were Black and 33.6% male. Participants with MCI were more likely to be Black (58.3% vs 33.7%%, p=0.007) and have lower RHI (1.93 vs 2.27, p=0.004) compared to NC. RHI was an independent predictor of MCI with a 96% adjusted greater odds of MCI per unit reduction in RHI. Black race remained an independent predictor of MCI (OR 2.90, 95% CI [1.16, 7.56]). RHI was lower in Black compared to White participants (1.86 vs 2.37, p<0.001). There was no heterogeneity in the impact of RHI on MCI. In a casual mediation analysis, MCI was mediated via RHI more in Black than in White participants (proportion mediated 24.2% vs 18.4%, p=0.034) after multivariate adjustment.

Conclusions:
Peripheral MVD, measured as RHI, was independently associated with MCI. Furthermore, Black participants exhibited lower RHI levels, a higher prevalence of MCI, and potentially mediated MCI through RHI to a greater extent compared to their White counterparts.
Abstract 13948: Real World De-Escalation Practices in Genotype Guided P2Y12 Inhibitor Therapy and Pharmacoeconomic Implications
Authors: Maryniak Andrii , Van Heukelom Joel , Massmann Amanda , Schultz April , Weaver Max , Hajek Catherine , Stys Tom P
Published: December 2023

Background:
Tailored P2Y12 inhibitor therapy is gaining popularity and is described as a method to balance safe and effective prescribing of clopidogrel. Based on previous work, 28% of our patients with CYP2C19 genotyping do not metabolize clopidogrel effectively (intermediate or poor metabolizers).

Aim:
We aim to describe the economic impact of a guided P2Y12 inhibitor strategy and the practice of escalation (clopidogrel to ticagrelor/prasugrel) and de-escalation (ticagrelor/prasugrel to clopidogrel) practices at a single health system. We hypothesize a guided approach is economically feasible vs. a universal ticagrelor or prasugrel approach. We also aim to determine how quickly clinicians escalate or de-escalate in response to CYP2C19 results.

Methods:
3-year (2020-2022) data was collected from our EMR. Annually an average of 950 patients received CYP2C19 testing to guide P2Y12 inhibitor therapy (n=2799), and an average of 316 patients were either escalated or de-escalated (n=949). Of the 2799 patients, clopidogrel was most often the initial P2Y12 inhibitor (n=2240), followed by ticagrelor (n=525), and prasugrel (n=34). We estimated overall medication and CYP2C19 testing costs over the course of an average year (Figure 1) based on the assumption that over the course of 1-year patients would begin on 30 days of either ticagrelor, prasugrel, or clopidogrel and escalate/de-escalate therapy thereafter as guided by testing.

Results:
The time to escalation was similar if the CYP2C19 result was ordered before or after the first order for P2Y12 inhibitor therapy, median of 6.2 and 6.5 days respectively (p = .07). There was a difference in time to de-escalation based on time of CYP2C19 testing in comparison to medication ordering with a median time of 32.1 and 8 days when testing was ordered before initiation and after, respectively (p <.001).

Conclusion:
Overall, clinicians were highly responsive to CYP2C19 test results for both escalation and de-escalation of therapy.
Abstract 13977: Insulin-Like Growth Factor Binding Protein 7 is Associated With Development of Cell Senescence and Progression of Coronary Atherosclerosis
Authors: Sukhanov Sergiy , Higashi Yusuke , Danchuk Svitlana , Snarski Patricia , Delafontaine Patrice
Published: December 2023

Introduction:
Cellular senescence, an irreversible cell cycle arrest, has been associated with atherosclerosis. Senescent cells (SC) secrete proinflammatory molecules contributing to disease progression. Insulin-like growth factor binding protein 7 (IGFBP7) binds IGF-1 and also interacts with IGF-1 receptor, suppressing intracellular IGF-1 signaling. IGFBP7 has been linked to heart failure-associated cell senescence.

Hypothesis:
We hypothesize that SC secrete IGFBP7, and IGFBP7 contributes to atherogenesis.

Methods:
Premature cell senescence was induced by treatment of smooth muscle cells (SMC) with H2O2. IGFBP7 levels were measured by immunoblotting of cell lysates and conditioned media (CM) and by immunohistochemistry in Apoe-null mice and in Rapacz hypercholesterolemic pigs. Binding of IGFBP7 with IGF-1 receptor was quantified by proximity ligation assay.

Results:
H2O2-treated SMC have marked increase in expression of the senescence markers beta-galactosidase (SA-βGal) and γH2A.X, and 3-fold (P<0.05) increase in IGFBP7 in cell CM. Abundant senescent SMC (αSMA
+
/SA-βGal
+
) were detected in fibrous cap’s plaque in murine innominate artery and these cells had increased IGFBP7 compared to SMC in the vascular media. Increased IGFBP7 levels (1.8-fold increase, P<0.05) were also detected in porcine coronary plaque and IGFBP7 upregulation correlated with elevated IGFBP7/IGF-1 receptor binding. These data suggest a mechanistic link between senescence, IGFBP7 upregulation and atherogenesis. SMC were incubated with CM from senescent SMC (or non-senescent controls) to determine if SC-secreted IGFBP7 inhibits IGF-1 signaling. Preincubation with CM from SC inhibited IGF-1-induced Akt phosphorylation, however co-incubation with anti-IGFBP7 antibody reversed this effect, indicating that IGFBP7 in the CM mediates the inhibitory effect on IGF-1 signaling.

Conclusions:
We have shown that SMC senescence induced IGFBP7 and that high IGFBP7 levels were associated with senescent SMC in the atherosclerotic plaque. IGFBP7 inhibits IGF-1 signaling in vitro and binds IGF-1 receptor in plaque SMC. Our results suggest a novel role of IGFBP7 in senescence and in atherogenesis and identify IGFBP7 as a potential target for anti-atherogenic therapy.
Abstract 13979: Titin-Truncating Variants Predispose to Dilated Cardiomyopathy in Patients Genetically Similar to African Reference Populations
Authors: Depaolo John , Bornstein Marc , Judy Renae , Levin Michael , Arany Zoltan , Damrauer Scott M
Published: December 2023

Introduction:
Heterozygous mutations within the
TTN
gene can cause the translation of shortened forms of the titin protein known as titin-truncating variants (TTNtvs) leading to dilated cardiomyopathy (DCM) among certain individuals. We previously reported an odds ratio (OR) of 18.7 for DCM among individuals genetically similar to the European reference population (EUR) with high percentage spliced in (hiPSI) TTNtvs, however we were unable to show a similar relationship among individuals genetically similar to the African reference population (AFR).

Methods:
Penn Medicine Biobank volunteers with whole exome sequencing were screened for TTNtvs with minor allele frequency <0.001 and percent spliced in >0.9. Participants were also screened for a DCM diagnosis defined using
International Classification of Diseases, ninth and tenth revision
diagnoses codes. Left ventricular ejection fraction (LVEF) values were extracted from structured transthoracic echocardiography reports. Logistic and linear regression were employed to evaluate the association between hiPSI TTNtvs and DCM or LVEF adjusting for age, sex, and first five genetic principal components.

Results:
Of the 43,731 participants with sequencing data, 11,136 (27.1%) were genetically similar to the AFR reference population, 50.3% were male, and the median age was 57.8 years (IQR: 44.9-69.5 years). One percent (418 individuals) had a hiPSI TTNtv. The age- and sex-adjusted OR of having DCM was similar among AFR and EUR participants carrying hiPSI TTNtvs (AFR OR: 4.37, 95% CI 2.68 to 7.13,
P
< 0.001; EUR OR: 5.86, 95% CI 4.58 to 7.49,
P
< 0.001; meta OR: 5.48, 95% CI 4.31 to 6.97,
P
< 0.001). Among those individuals with echocardiography data available, hiPSI TTNtvs were associated with significantly decreased minimum LVEF independent of genetic reference population similarity (EUR β: -10.08, 95% CI -12.71 to -7.44,
P
< 0.001; AFR β: -12.83, 95% CI -18.39 to -7.27,
P
< 0.001; Meta β: -10.58, 95% CI -12.96 to -8.20,
P
< 0.001).

Conclusions:
Our analysis demonstrates a strong association between hiPSI TTNtv and both DCM and minimum LVEF in diverse populations suggesting that genetic testing and counseling recommendations should not differ between these populations.
Abstract 14002: Endovascular Embolization and Coiling for an Intracranial Aneurysm in a 9 - Month Old Infant With Kawasaki Disease- A Unique Case Report
Authors: Basheer Noufal , Raj Aiswarya , Rafeeque P K Mohammed , K Prakash Midhun , Alapatt Paul J
Published: December 2023

Introduction:
Cerebrovascular involvement is rare in Kawasaki disease.We present a unique case of such an infant who developed intraventricular haemorrhage and was diagnosed with an intracranial aneurysm.

Case Report:
A 9-month-old female infant was referred to us with 5 days of high-grade intermittent fever & watery diarrhoea that did not respond to routine care. On arrival, she was stable with WBC count 20,000/UL, CRP 111 mg/L & ESR 85 mm/hr.She continued to have fever spikes and Echocardiography revealed dilated left coronaries with a LAD Z score of +2.92. Hence, by pediatric guidelines, she was started on IVIg (2g/kg) for Kawasaki disease. Repeat echocardiography 2 days later showed reduction in coronary prominence. On Day 10, the child developed episodes of abnormal posturing and respiratory failure. MRI brain showed intraventricular haemorrhage in dependent horns of bilateral lateral, 3rd and 4th ventricles and subarachnoid haemorrhage. CT angiography showed a saccular aneurysm at the junction of V4 segment of right vertebral artery & basilar artery (Figure 1). She underwent endovascular embolization, coiling of aneurysm& omaya reservoir insertion(Figure 2). She was weaned off supportive care & recovered well.

Conclusion:
Unlike fe existing reports, haemorrhage occurred during active phase of the disease and not years after diagnosis. To our knowledge, this is the first report of endovascular management of aneurysmal subarachnoid haemorrhage in KD in an infant. This uncommon presentation in an infant warrants discussion on whether routine screening of all children suspected of Kawasaki disease for extracardiac aneurysms might be potentially life-saving.
Abstract 14020: Five-Year Trends in Risk Factors for Cardiovascular Disease Among Adolescents in the United States
Authors: Hasan Ali , Ramphul Kamleshun , Ahmed Raheel , Farhan Muzammil , Hassan Azeem , dachepally rashmitha , Almasri Murad , Ahmad Hasan , Carver Caleb , Jeelani Mohammad Saddam , Jamil Yumna , Bilal Maham , Ahmad Javed , Memon Rahat A , Sakthivel Hemamalini
Published: December 2023

Introduction:
Cardiovascular disease is the leading cause of death in the United States (US) and worldwide. Past studies have demonstrated a rise in sedentary life-style among adolescents. We aim to provide an up-to-date representation of the prevalence of multiple cardiovascular risk factors amongst adolescents in the US.

Methods:
We queried hospitalization records of adolescents of ages 10-19 years (inclusive) via the 2016-2020 National Inpatient Sample, a set of de-identified records provided by HCUP, AHRQ and partners. The trends of several risk factors were estimated (per 100,000 hospitalization) via linear-by-linear analysis as per past studies of the database.

Results:
Our study found an increasing trend in prediabetes (41 per 100,000 in 2016 to gradually reach 309 per 100,000 in 2020, ptrend<0.01), hypertension (2334 per 100,000 in 2016 to reach 2756 per 100,000 in 2020, ptrend<0.01), diabetes (5119per 100,000 in 2016 to reach 5733 per 100,000 in 2020, ptrend<0.01), obesity (6153 per 100,000 in 2016 to reach 8221 per 100,000 in 2020, ptrend<0.01), smoking (8166 per 100,000 in 2016 to reach 9117 per 100,000 in 2020, ptrend<0.01), and family history of ischemic heart disease or cardiovascular disease (1687 per 100,000 in 2016 to reach 1922 per 100,000 in 2020, ptrend<0.01, ptrend<0.01) (Figure 1). In addition, the incidence of acute myocardial infarction (AMI) rose from 34 per 100,000 in 2016 to reach 68 per 100,000 in 2020 (ptrend<0.01). A similar rise in events of acute ischemic stroke (AIS) was seen with 123 cases per 100,000 reported in 2016 and this increased to 156 per 100,000 in 2020 (ptrend<0.01) (Figure 1).

Conclusion:
There is an alarming rise in various risk factors that can lead to future cardiovascular disease among adolescents. Furthermore, the incidences of AMI and AIS among adolescents are on the rise. Stronger health-related sensitization campaigns promoting healthier life-style should be mooted.
Abstract 14028: Stroke Location, White Matter Disconnections, and Neurodevelopmental Outcomes in Infants With Congenital Heart Disease
Authors: Selvanathan Thiviya , Guo Ting , Peyvandi Shabnam , Synnes Anne , Chau Vann , Ly Linh , BARKOVICH ANTHONY J , Seed Mike , McQuillen Patrick S , Miller Steven P
Published: December 2023

Objectives:
Infants with congenital heart disease (CHD) are at risk for stroke, although associations with neurodevelopmental outcomes have varied. In adults with stroke, location and altered structural connectivity (disconnections) have been linked to neurologic symptoms. We assessed whether stroke (1) location and (2) white matter disconnections are related to neurodevelopment in infants with CHD.

Methods:
Infants underwent pre- and post-operative brain MRI in prospective studies at 3 centres (UBC, UCSF, SickKids) and completed 18-month neurodevelopmental assessments using Bayley Scales with separate motor and cognitive composites. Adverse outcomes were defined as composite score <85. Strokes were manually segmented. Voxel-wise lesion symptoms maps (VLSM) were used to assess relationships between lesion location and neurodevelopment. Disconnectomes were generated using stroke segmentations as seeds for tractography and diffusion MRI from healthy controls. Voxel-wise disconnectome-symptoms maps (VDSM) of associations between structural disconnections and neurodevelopment were developed.

Results:
50 infants with strokes had neurodevelopmental outcomes data. Most strokes were small (<1/3 of arterial territory; n= 33) and in the left MCA territory (Fig 1A). However, strokes in the right basal ganglia and adjacent central white matter were most strongly associated with adverse motor and cognitive outcomes (Fig 1B). White matter disconnections extended beyond areas of injury (Fig 1C); these were extensive even in small strokes. Disconnections of tracts passing through the right basal ganglia were most strongly associated with adverse motor and cognitive outcomes (Fig 1D).

Conclusions:
Strokes involving the basal ganglia, particularly in the right hemisphere, were associated with worse motor and cognitive outcomes in infants with CHD. These data draw increasing attention to the right hemisphere in early-life stroke and neurodevelopment.
Abstract 14071: Plasma Protein Concentrations and Risk of Incident Cardiovascular Diseases in the UK Biobank
Authors: Pournamdari Ashley B , Schuermans Art , Lee Jiwoo , Bhukar Rohan , Small Aeron , Hornsby Whitney , Koyama Satoshi , Honigberg Michael C , Natarajan Pradeep
Published: December 2023

Introduction:
Profiling of plasma proteins has the potential to improve diagnosis, predict disease and reveal new biologic pathways for cardiovascular disease (CVD).

Objectives:
We tested the associations of circulating proteins with new-onset coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), and aortic stenosis (AS) in the UK Biobank.

Methods:
The initial dataset consisted of 52,705 individuals and 1,463 proteins measured using the Olink platform. A total of 47,665 unrelated individuals without prevalent CVD and 1,459 proteins were retained after quality control. Cox proportional hazards models were used to evaluate associations of protein levels at baseline with incident CAD, AF, HF, and AS. Models were adjusted for age, age
2
, race, first ten principal components of genetic ancestry, sex, smoking, BMI, SBP, antihypertensive and lipid-lowering medication use, DMII, serum creatinine, LDL and HDL cholesterol, and Townsend deprivation index. The four outcomes were incorporated as time-varying covariates.

Results:
Among the 47,665 individuals, mean (SD) age was 56.8 (8.2) years, 25,674 (53.9%) were female, and 44,691 (93.8%) white. Over a median follow-up of 11.1 years, there were 2,941 (6.2%), 2,502 (5.2%), 1,470 (3.1%) and 420 (0.9%) incident cases of CAD, AF, HF, and AS, respectively. Multivariable-adjusted Cox regression revealed 270, 156, 385, and 21 significant associations (P < 8.6 x 10-6) for CAD, AF, HF, and AS, respectively. Fifteen biomarkers overlapped across all outcomes. The strongest associations for CAD, AF, HF, and AS were with GDF-15 (HR = 1.33, 95% CI = 1.28 - 1.39), NT-proBNP (HR = 1.83, 95% CI = 1.75 - 1.91), HE4 (encoded by WFDC2; HR = 1.67, 95% CI = 1.57 - 1.77), and GDF-15 (HR = 1.51, 95% CI = 1.43 - 1.59), respectively. NT-proBNP, IGFBP-4 and HE4 were the strongest overlapping associations.

Conclusions:
High-throughput proteomics may offer new mechanistic insights and improve risk prediction for common CVDs.
Abstract 14074: Prodromal Symptom Cluster is Associated With Length of Hospital Stay After Cardiac Arrest Resuscitation
Authors: Martins Oliveira Izabela , Gengo E Silva Butcher Rita De Cassia
Published: December 2023

Introduction:
Little is known about the impact of cardiac arrest prodromal symptom clusters on survival after resuscitation.

Hypothesis:
Clusters of prodromal cardiac arrest symptoms are associated with the length of hospital stay until death or hospital discharge after resuscitation.

Methods:
This retrospective study included records of in-hospital and out-of-hospital cardiac arrest victims referred to a University Hospital in Brazil between 2010 and 2020. Data concerning the prodromal symptoms and length of hospital stay until death or hospital discharge were collected. Symptom clusters were examined by multiple correspondence analyses. Survival analysis and comparisons between those with and without symptoms were done by the Kaplan-Meier method and the Log-Rank test.

Results:
There were 120 eligible records (58.7 years old, 54.2% female, 86.7% White). Prodromal symptoms began during the 24 hours preceding the event in 67.2% of the victims; 64.1% had a return of spontaneous circulation. There were three symptom clusters. Symptoms of cluster 1 (dyspnea, cough, and edema), cluster 2 (mental confusion, restlessness, palpitations, reports of skin color changes, sweating, malaise, and stroke symptoms), and cluster 3 (fever, level of consciousness alterations, syncope, chest pain, abdominal pain, headache, and nausea), were found in 50.0%, 18.3%, and 54.1% of the records, respectively. Only individuals with symptoms of cluster 2 (Figure 1) had significantly lower lengths of hospital stay due to death than those without such symptoms (p = .04).

Conclusions:
Prodromal cardiac arrest symptoms occur in clusters that may indicate a worse prognosis after resuscitation.
Abstract 14081: Higher Fish Intake and a Healthy Lifestyle May Be Associated With a Lower Platelet Count/Lymphocyte Count Ratio: Implication for the Anti-Atherosclerotic Effect of Fish Intake
Authors: Monden Masaki , Tani Shigemasa , Yagi Tsukasa , Ashida Tadashi , Kuronuma Keiichiro , Matsumoto Naoya , Okumura Yasuo
Published: December 2023

Introduction:
Higher fish intake and healthy lifestyle behaviors are associated with a reduced risk of atherosclerotic cardiovascular disease (ASCVD). A higher platelet count/lymphocyte count ratio (PLR), an inflammatory predictive marker of ASCVD, is reportedly associated with a higher incidence of CVD.

Hypothesis:
We hypothesized that higher fish intake would be associated with lower PRL, and a healthy lifestyle would also be associated with lower PLR.

Methods:
We conducted a cross-sectional study between April 2019 and March 2020 at the Health Planning Center of Nihon University Hospital in a cohort of 5957 participants (average age, 46.7 ± 12.9 years; 58.9%, men) with no history of ASCVD. We calculated the amount of fish intake based on the average number of days of fish intake per week and data from the Japanese National Health and Nutrition Survey.

Results:
The average weekly frequency and amount of fish intake were 2.25 ± 1.30 days and 140.5 ± 86.7 g, respectively. As the weekly fish intake increased (< 50, 50-100, 100-150, 150-200, 200-250, 250-300, and ≥ 300 g), the PLR significantly decreased (p < 0.0001). A multivariable logistic regression analysis identified higher fish intake as an independent determinant of a lower PLR. Aerobic exercise was also an independent negative determinant of PLR. Furthermore, with increasing frequency of fish intake, the proportion of participants engaging in habitual aerobic exercise increased (p < 0.0001).

Conclusions:
The results suggest that a higher fish intake and a healthier lifestyle related to fish intake habits are associated with a lower PLR and thus may exert beneficial anti-inflammatory effects. This association may explain the preventive effects of fish intake on ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.
Abstract 14098: Epidemiology and Clinical Outcomes of Cardiac Arrhythmias in Pulmonary Arterial Hypertension
Authors: Yinadsawaphan Thanaboon , Suppah Mustafa , Ravi Srekar N , FARINA JUAN , Scott Robert L , Sorajja Dan
Published: December 2023

Background:
There is limited evidence regarding the impact of cardiac arrhythmias in patients with pulmonary arterial hypertension (PAH). We aim to comprehensively investigate the epidemiology and clinical outcomes of cardiac arrhythmias in patients with PAH.

Methods:
In a retrospective cohort study including 512 PAH patients from 2001-2021 at 3 Mayo Clinic sites, PAH patients were identified via echocardiogram, pulmonary function tests, and right heart catheterization. Demographic data at PAH diagnosis and clinical outcomes over a 10-year period were collected. The PAH patients were categorized into three groups based on arrhythmic onset: 1) patients with arrhythmia prior to PAH diagnosis, 2) patients diagnosed with arrhythmia during 10-year PAH follow-up, and 3) patients without arrhythmia during 10-year PAH follow-up. Survival outcomes were analyzed using multivariable Cox proportional hazards regression, adjusted with the REVEAL 2.0 score.

Results:
Among 512 PAH patients (mean age 56.1 years, 81.8% female), the prevalence of cardiac arrhythmias at PAH diagnosis was 10.5%. The cumulative incidences of new-onset arrhythmias at 1, 5, and 10 years were 6.6%, 18.4%, and 29.2%, respectively. Patients with arrhythmia diagnosed before and after PAH diagnosis showed significantly higher all-cause mortality rates with adjusted HR of 2.06 [95% CI 1.36-3.12] and 1.57 [95% CI 1.17-2.20] respectively (Figure 1). Similarly in both arrhythmic groups, there was a shorter median time to the first all-cause hospitalization (9.5 and 15.9 months vs. 21.2 months) and a higher number of all-cause hospitalizations (0.38 and 0.64 times per year vs. 0.10 times per year) compared to the non-arrhythmic group.

Conclusions:
Cardiac arrhythmias can develop in nearly one-third of PAH patients within 10 years of PAH diagnosis and independently contribute to increased mortality and hospitalization frequency.
Abstract 141: Automated Head-Up Cardiopulmonary Resuscitation Increased End Tidal Co2 in Patients With Out-of-Hospital Cardiac Arrest Compared With Conventional CPR: A Prospective Before-After Interventional Study
Authors: Debaty Guillaume , Duhem Helene , Segond Nicolas , sanchez caroline , Crespi Christophe , Jaeger Deborah , Chouihed Tahar , Lurie Keith G , Labarere José
Published: December 2023

Background:
Little is known in humans about the physiological effects of the combination of automated Head-Up cardiopulmonary resuscitation CPR, active compression-decompression CPR and an impedance threshold device (ITD). This new approach, termed AHUP-CPR, improves perfusion of vital organs and lowers intracranial pressure compared with conventional (C)CPR in animal models of cardiac arrest. This study tested the hypothesis that AHUP-CPR treatment would increase end tidal CO2 (ETCO2), a circulation surrogate, more than C-CPR in out-of-hospital cardiac arrest (OHCA) patients.

Method:
Prospective before-after interventional study of witnessed OHCA patients. C-CPR and AHUP-CPR were performed by firefighters who measured ETCO2. AHUP-CPR was delivered using a LUCAS AD (5 cm of compression and 3 cm active decompression) (Stryker Medical, USA), an EleGARD Patient Positioning System (AdvancedCPR Solutions, USA), and an ITD (ResQPOD-16, Zoll, USA). The study was performed in the greater Grenoble France region in four different fire stations. The primary endpoint was the measurement of maximum EtCO2 during CPR. Results are presented as mean ± standard deviation.

Results:
Baseline characteristics (age, sex, arrest location, initial rhythm, bystander CPR, witnessed) were not statistically different between groups.EtCO2 was higher for patients treated with AHUP-CPR (n=63) compared to the C-CPR (n=59) (41±18 vs. 30.2 mmHg, p<0.001). This difference was significant for shockable (45±13 vs. 34±12 mmHg, p=0.03) and non-shockable (40±19 vs. 28±13 mmHg, p=0.004) rhythms, respectively. The calculated difference between the maximum and first recorded ETCO2 values was 6.3 ± 20.4 in the C-CPR arm versus 21.1 ± 20.6 in the AHUP-CPR group (P<0.001). A total of 29% (n=18) of the AHUP patients vs. 22 % (n=13) were admitted alive to the hospital (P=0.34).

Conclusion:
Results from this first prospective clinical trial on AHUP-CPR demonstrated that ETCO2 values were significantly higher after AHUP-CPR versus C-CPR, regardless of the presenting rhythm. Using ETCO2 as a surrogate for circulation, these findings confirm animal studies showing AHUP-CPR provides significantly more vital organ blood flow to patients in OHCA compared with C-CPR.
Abstract 14106: Predicting Persistently Elevated Pulmonary Artery Diastolic Pressure Despite Adequate Diuresis
Authors: Allinson Francis , Ng Daniel , Puglisi Leah , Srivastava Ajay
Published: December 2023

Introduction:
Patients with chronic HF can be challenging to manage via ambulatory hemodynamic monitoring due to persistent elevations in pulmonary artery diastolic pressure (PADP) despite appropriate diuresis. Knowing what factors predict persistently elevated PADP on CardioMEMS can help guide patient selection and management.

Hypothesis:
We propose that underlying heart failure phenotypes exist that are less likely to respond to hemodynamic guided management.

Methods:
This was a single-center, retrospective analysis of Scripps Clinic patients who underwent CardioMEMS implantation from June 2015 to September 2022. A total of 115 patients were included and divided into two cohorts based off their average PADP calculated using their last 4 transmissions. The normal PADP cohort included patients with an average PADP ≤ 20 mmHg while the persistently elevated PADP cohort included patients with a PADP > 20 mmHg.

Results:
Of the 115 patients analyzed, 62 patients were in the normal PADP cohort while 53 patients were in the persistently elevated PADP cohort. There was no significant difference between baseline demographic data, except for renal function, as shown in Table 1. There was a significant difference between the two groups when comparing pulmonary pressures and PVR via right heart catheterization prior to CardioMEMS implantation, but not when comparing pulmonary artery pressure obtained via echocardiogram (Table 1). The persistently elevated PADP cohort had a significantly lower GFR and were on higher doses of loop diuretics than the normal PADP cohort.

Conclusions:
Our analysis shows that renal function, baseline invasive hemodynamic data consistent with pulmonary vascular remodeling and decreased cardiac index can help predict patients with persistent elevations in their PADP on ambulatory hemodynamic monitoring and highlights the importance of early HF management before vascular remodeling complicates hemodynamic guided management.
Abstract 14108: Eicosapentaenoic Acid and Docosahexaenoic Acid and Their Association With Oral Inflammatory Markers in Subjects With Clinical Coronary Artery Disease
Authors: Ahmad Bushra , Malik Abdulaziz , Daher Ralph , Welty Francine K
Published: December 2023

Background:
Our group previously reported that subjects with coronary artery disease (CAD) randomized to the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), had lower levels of blood inflammatory markers and prevention of progression of non-calcified coronary plaque. Macrophage inhibitory protein (MIP)-1β is an inflammatory chemokine expressed by T cells in human plaques; circulating levels are increased in patients with atherosclerosis. The relation between EPA+DHA supplementation and oral inflammatory markers is unclear.
Aim:
To determine if EPA+DHA supplementation lowers levels of oral inflammatory markers.

Methods:
Subjects with clinical CAD were randomized to EPA+DHA, 3.36 g daily, or none for 30 months; 199 underwent a dental exam. Gingival crevicular fluid was collected at baseline and 30 months and analyzed for inflammatory markers.

Results:
MIP-1-β level was significantly lower in the EPA+DHA group compared to control at 30 months in the left upper quadrant of the mouth but not in the right upper quadrant (Table). This difference could potentially be explained by handedness. For example, Right-handed people tend to brush the left side of the mouth better whereas left-handed individuals and ambidextrous individuals have better brushing skills on the right side of the mouth. Other inflammatory markers (MCP, TNF-a, IL-1 and IL-6) were not different between groups on either side.

Conclusions:
Subjects with CAD randomized to EPA+DHA had reduced levels of the oral inflammatory marker, MIP-1β, at 30 months, suggesting that EPA+DHA can confer oral health benefits in addition to lowering systemic inflammation. For greatest benefit, brushing equally on both sides of the mouth should be encouraged, for which a powered toothbrush can help as it doesn’t rely on manual dexterity and handedness. Future research should examine whether the benefit of omega-3 fatty acids on oral health increases the benefit on coronary plaque.
Abstract 14140: Management and Outcomes of Bacteremia After Transvenous Lead Extraction Complicated by Retained Lead Fragments
Authors: DeVries William M , Danso Emmanuel , Francis Emma , Robl Tanner , Kettelkamp Nicholas , Cushing Jacob , Berenbom Loren D , Dendi Raghuveer , Noheria Amit , Pimentel Rhea C , Ramirez Rigoberto , Reddy Madhu , anderson john , Sheldon Seth H
Published: December 2023

Introduction:
Complete hardware removal is indicated for cardiovascular implanted electronic devices (CIED) infection. While transvenous lead extraction (TLE) is often successful in removing the entire device, some patients are left with residual hardware due to lead breakdown or unsuccessful attempts at removal. We sought to assess the outcomes and management in patients with retained CIED components that can be a nidus for ongoing infection.

Methods:
Single center retrospective case series among patients with lead extraction between 2010 and 2022.

Results:
There were 9 of 930 TLE patients (1%) who met study criteria (age 68 ± 23 yrs, 78% men, 67% ICD, 44% CRT, oldest lead 10.1 yrs IQR 6.1-22.2, combined lead age 21.2 yrs IQR 14.7-54.9). Two patients (22%) had epicardial leads as well. The majority of patients (n=8/9, 89%) had systemic infection, including lead vegetations in 22% (n=2). The most common infection organism was Staphylococcus aureus (n=5, 56%). Residual CIED components included lead tips (n=4, 44%), epicardial leads (n=2, 22%), entire intravascular lead portion (n=2, 22%), and a remnant ICD coil remaining in the SVC (n=1, 11%). TLE attempt was halted in 1 patient with a right atrial perforation during extraction (only removed 4/6 leads) and another patient with unsuccessful removal via laser, mechanical, and snaring attempts. Device reimplantation was performed in 4 patients (44%). The patient with the RA perforation underwent reimplantation of an epicardial system at the time of repair. Median follow-up was 0.9 years (IQR 0.4-7.2). Three patients (33%) were managed with indefinite antibiotic suppression, while the median antibiotic duration for the remainder was 35 days (IQR 14-43). Two patients (22%) had recurrent infections, both of which occurred despite the use of indefinite antibiotic suppression. None of the patients with residual lead tip alone had subsequent infections or were managed with suppressive antibiotics.

Conclusion:
Recurrent infection can be problematic when retained lead components are present after TLE and occurred despite the use of indefinite suppressive antibiotics in some patients. Further investigation is necessary to determine if the risk of recurrent infection varies by the type of residual CIED components.
Abstract 14150: Glycolysis and Cardial Fibrosis
Authors: Zhu Zhaowei , Han Bing , Zhang Zheng , Zhou Shenghua
Published: December 2023

Introduction:
Cardiac fibrosis is a significant global issue, which however has limited therapeutic options. 6 - phosphofructo - 2 - kinase/fructose - 2,6 - biphosphatase 3 (PFKFB3) is established to play a critical role in the process of glycolysis. However, its specific role in the pathogenesis of cardiac fibrosis is still not well understood.

Hypothesis:
PFKFB3 plays a critical role in cardial fibrosis.

Methods:
To determine the role of PFKFB3 in cardiac fibroblast (CF) activation and fibrosis, single - cell RNA sequencing analysis was applied to identify the metabolic changes of fibroblast subclusters in cardiomyopathy. PFKFB3 inhibition with genetic (

Pfkfb3
+/-

) mice or pharmacological (3PO) approach was used to demonstrate the role of PFKFB3 in cardiac fibrosis with animal models, induced by isoproterenol (ISO) or left coronary ligation. The role of PFKFB3 in primary CFs activation was confirmed by gene inhibition or overexpression. Recombinant PFKFB3 was used to test its extracellular role in CFs activation and inflammation. Serum PFKFB3 level was also tested from patients with cardiomyopathy.

Results:
We found that glycolysis changes most in cardiac myofibroblasts (myoCFs) in cardiomyopathy. PFKFB3 increased significantly in both cardiac fibrotic regions and myoCFs induced by TGF-β1. Inhibition of glycolysis, via several approaches, blunted TGF-β1-induced activation, proliferation and migration ability of myofibroblasts and demonstrated therapeutic benefit in cardiac fibrosis in mice. PFKFB3 released from myoCFs facilitated the activation of CFs and promoted the inflammatory response. Mechanistically, HIF-1α is required in TGF-β1 induced glycolysis. Plasm PFKFB3 was also found to be a biomarker for cardiac fibrosis in patients with cardiomyopathy.

Conclusions:
PFKFB3 is a candidate target for cardiac fibrosis.
Abstract 14154: Myotonic Dystrophy and Stress Induced Cardiomyopathy
Authors: Chanda Anindita , Garikapati Sriram , Konstantinidis Ippokratis , Elsadany Mohammed , Saucier Stephanie , McMahon Sean
Published: December 2023

Myotonic dystrophy type 1 (MD1) is an autosomal dominant neuromuscular disease that can affect skeletal, smooth, and cardiac muscle. Patients often have cardiac involvement such as conduction diseases, ventricular arrhythmia, sudden cardiac death, cardiomyopathy and pulmonary hypertension. We describe a patient with MD1 who suffered recurrent takotsubo cardiomyopathy.

Case:
A 39-year-old female with history of myotonic dystrophy type 1, takotsubo cardiomyopathy with recovered ejection fraction (EF) 50-55%, gastroparesis and orthostatic hypotension presented with chest pain, nausea, vomiting, dyspnea, and diaphoresis. Initially she was hypotensive and tachycardic. The initial physical exam revealed intact mentation, cachexia, 4/5 muscle strength in all four extremities, lack of JVD, warm and well-perfused extremities without edema. Notable lab findings included a lactic acid of 2.3 mmol/L, high sensitivity troponin of 5000 ng/L and proBNP of 1520 pg/mL. Her initial ECG revealed first degree AV block, left anterior fascicular block, ST elevations in leads V
2
-V
3
and T wave inversions in lateral leads. She was admitted for further evaluation. A transthoracic echocardiogram (TTE) showed an EF of 20-25% with apical akinesis and ballooning, with a small apical mural thrombus. She was started on a heparin drip and ischemic work up was deferred given her normal coronary arteries three years prior. Serial TTEs showed improvement of her EF to 54% within two weeks. She was managed with gentle diuresis but she was unable to tolerate guideline directed medical therapy (GDMT) due to symptomatic hypotension. Improvement in her symptoms was noted with the EF recovery.

Discussion:
There is currently no known association between takotsubo cardiomyopathy and myotonic dystrophy type 1. To our knowledge there is one case in the literature that reported a recurrent takotsubo cardiomyopathy in MD1 patient, and this case is the second. These two cases highlight the possibility that MD1 patients may be at risk of recurrent takotsubo cardiomyopathy. We believe that additional research is needed to investigate a possible causative relationship between the two disease entities.
Abstract 14158: Ceria/Iron Oxide and Silver/Iron Oxide Nanohybrids: New Classes of Materials for Theranostics of Cardiovascular Diseases
Authors: Ta Hang T
Published: December 2023

Introduction:
The need for efficient and biocompatible treatment methods that can simultaneously deliver imaging and therapeutic agents for combined diagnosis and therapy have resulted in the development of theranostic nanoparticles in recent times. Nanotheranostics represent one of the last frontiers in precision medicine and provide real-time information about drug biodistribution, release, and targeted treatment in vivo.

Hypothesis:
Here we aim to develop biocompatible smart nanomaterials for efficient theranostics of cardiovascular diseases.

Methods:
We have developed various hybrid materials based on metal and metal oxide such as iron oxide, ceria, and silver for diagnosis and treatment of thrombosis, atherosclerosis and inflammatory diseases. Iron oxide offers magnetic resonance imaging (MRI) capability. Ceria provides antioxidant and anti-inflammatory effects. The incorporation of silver onto the particles not only provides photoacoustic imaging capability but also allows photothermal therapy. The developed nanohybrids were labelled with fluorescence molecules to enable optical imaging, and also tagged with targeting ligands for targeted delivery of the materials.

Results:
The ceria/iron oxide nanohybrids showed excellent theranostic property in a liver inflammation mouse model, and in an atherosclerosis model. MRI was successfully employed to monitor the delivery of the materials and detect the inflammation, and atherosclerosis. The particles could reverse liver inflammation and inhibit atherosclerosis progression while did not show any adverse effects systemically. The other nanohybrids, silver/iron oxide, exhibited multimodal imaging capability where both MRI and photoacoustic imaging could be used to image the materials and thus allowed the detection of thrombosis in mouse models. Triggered by 808nm light, the nanoparticles could induce excellent thrombolysis effect and completely restored blood flow in the clotted arteries. Interestingly, this material did not show any systemic adverse effect.

Conclusions:
Our data show that these new classes of materials are promising theranostic approaches for imaging and treating thrombosis and inflammation diseases such as atherosclerosis and liver inflammation.
Abstract 14193: Safety and Efficacy of Catheter Ablation of Atrial Fibrillation With Pulsed Field Ablation versus Thermal Energy Ablation: A Systematic Review and Meta-Analysis
Authors: Aldaas Omar M , Aldaas Amer M , Han Frederick , Hoffmayer Kurt S , Krummen David E , Ho Gordon , raissi farshad , Birgersdotter-Green Ulrika , Feld Gregory K , Hsu Jonathan C
Published: December 2023

Introduction:
Pulsed field ablation (PFA) has emerged as a novel energy source for the ablation of atrial fibrillation (AF) using ultrarapid electrical pulses to induce cell death via electroporation.

Hypothesis:
Ablation of AF with PFA will be more safe and as effective as thermal energy sources.

Methods:
We performed an extensive literature search and systematic review of studies that evaluated the safety and efficacy of ablation of AF with PFA and compared these to landmark clinical trials of ablation of AF with thermal energy sources. Freeman-Tukey double arcsine transformation was used to establish variance of raw proportions followed by the inverse with the random effects model to combine the transformed proportions and generate the pooled prevalence and 95% confidence intervals (CI).

Results:
We included 24 studies for a total of 5,203 patients who underwent ablation of AF. Among these patients, 54.6% (n=2,842) underwent PFA and 45.4% (n=2,361) underwent thermal ablation. There were significantly fewer periprocedural complications in the PFA group (2.05%; CI 0.94-3.46) compared to the thermal ablation group (7.75%; CI 5.40-10.47) (p=0.001). When comparing AF recurrence up to one year, there was a statistically insignificant trend towards a lower prevalence of recurrence in the PFA group (14.24%, CI 6.97-23.35) compared to the thermal ablation group (25.98%, CI 15.75-37.68) (p=0.132) as shown in Figure 1.

Conclusion:
Based on the results of this meta-analysis, PFA was associated with lower rates of periprocedural complications and similar rates of recurrent AF with up to one year of follow-up when compared to ablation with thermal energy sources.
Abstract 14196: Prevalence of Ischemic and Nonischemic Sudden Cardiac Death Differs by Sex and Age
Authors: Eskuri Anette , Vahatalo Juha , Pakanen Lasse , Holmstrom Lauri , Perkiomaki Juha , Huikuri Heikki , Junttila Juhani
Published: December 2023

Introduction:
During the last decades the proportion of nonischemic sudden cardiac death (NI-SCD) seems to have increased in both sexes. In women the incidence of coronary artery disease (CAD) starts to increase after the menopause.

Aim:
The aim of this study was to illustrate how the amount and the proportions of ischemic SCD (I-SCD) and NI-SCD vary between women and men in different age groups.

Methods:
The Fingesture study consists systemically collected clinical and autopsy data of 5,869 SCD victims of Northern of Finland (21% women).

Results:
In women 6.7% of the SCDs occurred at the age < 50 years and in men 11.4% (P<0.001 for both). I-SCDs covered 75% (P<0.001) of the cases of which 80% were men (P=0.005). The proportion of NI-SCDs was higher in women in every age group. Proportion of I-SCDs started to increase rapidly in both sexes at the age of 40-44 years. In women aged 50-54 years 53% of the cases were I-SCDs. The gender difference in proportion of I-SCD was actually the smallest in age groups 40-49 years and after 70 years of age, and its largest in the middle in favor of men. (Figure 1).

After the age of 70 years the total amount of SCDs started to plateau in men and decrease in the amount of SCDs was seen in men after the age of 75 years as in women the plateau phase was not reached until the age of 80 years (Figure 2).

Conclusions:
Minority of the SCDs occur under the age of 50 years, especially in women. The proportion of NI-SCD was higher in women than in men despite the age but the proportion of I-SCD was remarkable already at pre- and perimenopausal age. The amount of I-SCD increased in women until the age of 80 years emphasizing the need of early primary and secondary prevention of CAD also in women not only in men.
Abstract 14222: Annual Vascular and Bleeding Outcomes in East Asian Poststenting Patients With Acute Coronary Syndrome: The BRIC-ACS II Trial
Authors: li dandan , Chen Yundai , Yu Yani , Tuo Xiaodan
Published: December 2023

Objective:
To determine the incidence of bleeding and thrombotic vascular events in the "real-world"acute coronary syndromes (ACS) Chinese patients over 1-year following stent implantation.

Background:
The balance between vascular and bleeding outcomes during dual antiplatelet therapy (DAPT) is a matter of considerable controversy, especially in Asian populations. In contrast to Europeans, Chinese patients experience more bleeding but less thrombotic events over aggressive DAPT with ticagrelor than after conventional clopidogrel.

Methods and Results:
From November 2017 till April 2020 we enrolled post-stenting ACS patients (n=5,515) from 30 tertiary hospitals with the strict 1-year follow-up (n=5.150). Only few 153(3.0%) patients developed MACE (a composite of all-cause death, myocardial infarction, ischemic stroke, or urgent coronary revascularization). The cumulative incidence of annual bleeding (BARC ≥2) was 5.8% (298/5150) among patients who completed 1year follow-up.The BARC ≥2 bleeding was almost twice higher 298 (5.8%) and was not associated with worsened MACE [CI:0.37 -1.67; P =0.52). Patients treated with ticagrelor (n=1620, 6.0%) had a significantly increased risk of bleeding than those treated with clopidogrel (n=2331; 4.1%) (HR=1.486; 95% CI:1.12-1.97; P=0.006), but similar risk of vascular MACE (2.7% vs 2.8%; HR= 0.94; 95% CI:0.64-1.38; P = 0.747).The factors independently associated with the comprehensive risk of BARC ≥2 bleeding and MACE , including female gender, renal insufficiency, peptic ulcer, atrial fibrillation, continuous use of ticagrelor and non-continuous DAPT. The discrimination of the nomogram model was further tested by the ROC curve (AUC value:0.610 (95% CI, 0.577-0.642 )).

Conclusions:
The annual incidence of BARC≥2 bleeding in ACS patients treated with PCI in China was almost twice higher (5.8%) than MACE (3.0%). DAPT with ticagrelor increased the bleeding rates with no trend towards MACE reduction. The trial was registered at the clinnicaltrials.org as NCT03402711.This study was sponsored by Sanofi.