bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17315: Black Patients With Heart Failure Living in Distressed Communities Disproportionately Experience Excess Risk of Mortality After Emergency Department Visit for Dyspnea
Authors: Kraevsky-Phillips Karina , Callaway Clifton W , Henker Richard A , Scott Paul , Al-Zaiti Salah S
Published: December 2023

Introduction:
Dyspnea is a frequent reason for seeking emergency care in patients with heart failure (HF). Social determinants of health play an important role in long term survival in this population. We sought to explore the association between community’s economic well-being and post-visit survival in patients with HF evaluated in the emergency department (ED) for dyspnea.

Methods:
This was a retrospective cohort study enrolling all consecutive patients with a history of HF and an ED visit for a chief complaint of dyspnea at one of 40 UPMC-affiliated hospitals in Western PA between 1/2018 and 12/2021. We automatically extracted limited tabular data from electronic health records (e.g., demographics, visit dates) and performed manual chart review to determine home community status according to Economic Innovation Group’s Distressed Communities Index (i.e., prosperous/comfortable vs mid-tier/at-risk/distressed). Primary outcome was all cause death, established by documented death in UPMC network inpatient or outpatient charts and through a manual obituary search to ascertain missing death dates through 5/2023. We used Cox regression to identify independent predictors of time-to-event (death) and plotted significant predictors using Kaplan-Meier analysis.

Results:
The sample included 1248 patients (age 73 ± 13, 53% female, 15% Black). Around 59% of patients lived in distressed communities, and 62% died during a mean follow up of 996 days. In multivariate Cox regression, age (HR=1.032, 95% CI 1.025-1.038) and non-Black race (HR=2.304, 95% CI 1.264-4.202) were associated with excess risk of mortality. There was a significant independent interaction between race and residence, with Black individuals living in distressed communities experiencing excess risk of death compared to their counterparts (HR=1.926, 95% CI 1.083-3.424). This interaction was not evident among individuals who were not Black.

Conclusion:
While elderly patients, who are predominantly White, experience excess risk of HF mortality irrespective to area of residence, Black patients living in distressed communities experience excess risk of mortality, independent of age, sex, and other potential risk factors.
Abstract 17326: Urine Exosomes Proteomics for Parenchymal Kidney Health in Heart Failure Patients With Mechanical Circulatory Support
Authors: Mondal Nandan K , Li Shiyi , Nordick Katherine V , Murrieta-Alvarez Ivan , Hochman-Mendez Camila , Shafii Alexis E , Liao Kenneth K , Walther Carl P
Published: December 2023

Introduction:
Kidney dysfunction frequently affects heart failure (HF) patients with left ventricular assist device (LVAD) support and is linked to unfavorable outcomes. However, the effects of LVAD support on parenchymal kidney health are uncertain. We performed a pilot study on urine exosome proteomics in LVAD recipients as they offer a non-invasive glimpse into kidney cellular states.

Methods:
We collected urine samples from 33 patients who underwent LVAD (HeartMate III) surgery between 01/2022-02/2023. Urine exosomes were isolated from the samples collected before the operation and on the 7th day after surgery. The exosome fraction underwent untargeted proteomics using LC-MS/MS and iBAQ quantification. Our investigation focused on identifying and studying kidney-enhanced proteins.

Results:
The exosomes isolated were verified by canonical exosome proteins (CD63, Hsp70) and TEM imaging (Fig.A,B), with 82.7% of exosomes between 51-120 nm (Fig.C). Over 7K strict genes were identified with an average of 1,150 proteins (Fig.D,E). In GO analysis, exosomes were the primary cellular compartment represented (Fig.F). A total of 176 kidney-enhanced proteins were present in >50% of samples. Differential expression analysis revealed 8 proteins with increased expression on the 7
th
day after surgery with FDR<0.1(Fig.G). The 2 top proteins were glutathione peroxidase 3 (GPX3, log2 FC 3.4 [95%CI 2.1-4.8]), and fatty acid binding protein 3 (FABP3, log2 FC 2.9 [95%CI 1.7-4.2]). Enrichment analysis (Fig.H) demonstrated pathway changes consistent with inflammatory and ischemic kidney damage, metabolic dysfunction, and fibrotic transformation, consistent with kidney stress from advanced HF and cardiac surgery.

Conclusions:
We have demonstrated the feasibility of urine exosomes for non-invasive parenchymal kidney health assessment in LVAD patients. Further investigation in a larger cohort with additional sampling points may be warranted.
Abstract 17335: Novel Functional Genomic Studies in Scn1bb Variant Associated With Brugada Syndrome and the Ameliorative Effect of Acacetin
Authors: Barajas-Martinez Hector , Di Diego Jose M , Patocskai Bence , Borbath Virag , Li Gui-Rong Li , Burashnikov Alexander , Hu Dan , Antzelevitch Charles N
Published: December 2023

Background:
Brugada syndrome (BrS) is a channelopathy associated with the development of life-threatening ventricular tachycardia and fibrillation (VT/VF). At present, pharmacological approaches to therapy are very limited.

Objective:
To evaluate the effect of an
SCN1Bb
variant and the effects of acacetin in experimental models of BrS.

Methods:
We evaluated the effect of acacetin in: 1) HEK293 cells expressing Kv4.3+
KChIP2
and Nav1.5+
SCN1B
using patch clamp techniques (22
O
C), 2) canine ventricular epicardial myocytes 3) coronary-perfused canine right (RV) preparations and 4) Langendorff-perfused canine whole-heart models of BrS in which the sodium channel blocker ajmaline or the calcium channel blocker verapamil, together with the transient outward current agonist NS5806 were used to provoke the arrhythmic phenotype.

Results:
Co-expression of
SCN5A
-WT+
KCND3-WT
with
KChIP2
+
SCN1Bb
-R214Q (variant associated with 3 cases of BrS and 1 case of sudden infant death (SIDS)), resulted in a 210% increase in total charge of the transient outward potassium current (I
to
) as well as a 56.5% reduction in sodium channel current (I
Na
) when compared to
SCN1Bb-WT
. In the absence of the mutation, acacetin inhibited I
to
with an IC
50
of 7.2±1.0 μM (n=3) in HEK cells, similar to the value obtained in native epicardial myocytes (6 μM). In the presence of the
SCB1Bb
mutant, IC
50
was dramatically reduced to 2.6±1 μM (n=5, p<0.05) Mean ±SEM. In the wedge and whole-heart models of BrS, acacetin dose-dependently reduced the epicardial action potential notch recorded from the RV or RVOT. Acacetin (5-10 μM) totally suppressed the electrocardiographic and arrhythmic manifestation of BrS, regardless of the pharmacologic model used to induce the arrhythmic phenotype. All repolarization defects were reversed, resulting in marked diminution of J waves leading to total suppression of VT/VF.

Conclusions:
Our findings demonstrate the ability of an
SCN1Bb
variant to dramatically shift the balance of current in the early phases of the RV epicardial action potential by reducing I
Na
as well as augmenting I
to
, thus predisposing to the development of the BrS phenotype. Our observations also hold promise for acacetin as a safe and effective pharmacologic treatment for BrS and some cases of SIDS.
Abstract 17372: Cardiac Magnetic Resonance in Takotsubo Disease: Impact on Outcomes and Resource Utilization
Authors: Narendrula Aparna , Issa Rochell , Chen David , Tang Wai Hong W , Nguyen Christopher , Kaelber David , Kwon Deborah H
Published: December 2023

Introduction:
Takotsubo cardiomyopathy (CM), characterized by transient left ventricular dysfunction, presents diagnostic and management challenges. The utility of cardiac magnetic resonance (CMR) in Takotsubo CM is uncertain. We investigate CMR's impact on outcomes and resource utilization in Takotsubo CM.

Methods:
A retrospective analysis was conducted with TriNetX. Two cohorts with Takotsubo CM, with and without CMR within 1 month of diagnosis, were matched for lipidemias, hypertension, diabetes, sarcoidosis, and heart diseases (n=1,422 per cohort), Risks assessed 30-day, 1- and 5-year outcomes, resource utilization, and medication/procedure usage.

Results:
The CMR group had 3.9% (1.5% vs 5.4%, p=0.000) lower risk of mortality within 30 days and 2.6% (4.6% vs 7.2%, p=0.003) lower risk between 1 and 5 years. Hospitalization rates were similar, while complication risks (cardiomyopathy, heart failure) were higher in the CMR group at 1 and 5 years. The CMR group had higher utilization of GDMT, with similar usage for some treatments. Risk of pacemaker or implantable defibrillator usage were 4.9% higher within 30 days (5.8% vs 0.8%, p=0.000) and 5.8% higher within 1 year (8.2% vs 2.5% p=0.000) in the CMR group.

Conclusions:
Takotsubo patients undergoing CMR exhibited increased risk of concomitant diagnoses of CM/heart failure/pericarditis, received treatments earlier in the disease course, and experienced lower risk of mortality. These results support utilization of CMR as a routine diagnostic imaging modality in patients with suspected Takotsubo CM for comprehensive evaluation to guide treatment decisions and improve patient prognosis.
Abstract 17378: A Novel Strategy in the Sequencing of HFrEF Therapy: An Upfront and Prompt Approach
Authors: Prosperi Silvia , Severino Paolo , Damato Andrea , Mariani Marco Valerio , Labbro Francia Aurora , Cestiè Claudia , Myftari Vincenzo , Germanò Rosanna , Maestrini Viviana , badagliacca roberto , Fedele Francesco , Vizza Carmine Dario
Published: December 2023

Introduction:
The latest HF European guidelines recommend the use of four different classes of drugs for HFrEF. Despite advances in treatment, some gaps remain to be filled. In particular, sequencing and timing of HF therapy administration are not clarified and different strategies have been proposed.

Hypothesis:
An early, upfront novel approach, based on prompt administration of BB, SGLT2i, ACEi/ARNI, and MRAs may prove beneficial in terms of HF rehospitalization and CV death risk reduction.

Aims:
To compare early sequencing of HFrEF GDMT with the conventional, stepwise strategy. The primary endpoint was a composite of HF rehospitalization and CV death. Secondary endpoints were the single events of the primary endpoint.

Methods:
This prospective, observational study included consecutive patients with a HFrEF diagnosis from the Cardiology department. They were divided based on treatment strategy. Group 1 (G1) was treated with a novel GDMT sequencing (in-hospital start of BB and SGLT2i, ACE-i/ARNI, and lastly adding MRAs within 30 days from discharge). Group 2 (G2) was treated with the conventional, stepwise GDMT sequencing. Comparison between the two groups has been performed at 6-month follow up.

Results:
The study included a total of 302 patients. 278 patients underwent follow up: 139 in G1 group and 139 in G2 group. The two groups did not show significant differences at baseline. No significant differences have been observed for the primary composite outcome (p= 0.135) and for CV mortality (p=0.642) between the two groups. HF rehospitalization risk was significantly lower in G1 group compared to G2 group (p<0.001).

Conclusions:
HFrEF patients treated with a novel GDMT sequencing, promptly initiated and completed within 30 days from discharge, have shown reduced risk of HF rehospitalization compared with the conventional strategy.
Abstract 17382: Black Patients With Heart Failure Consume Diets That Are More Proinflammatory and Higher in Micronutrient Insufficiencies Than White Patients
Authors: Kang JungHee , Lennie Terry A , Biddle Martha J , Chung Misook L , Moser Debra K
Published: December 2023

Background:
Black patients experience disparities in heart failure (HF) outcomes compared to their White counterparts. Differences in diet quality, dietary inflammatory potential, and micronutrient deficiencies may contribute to these disparities.

Aims:
To compare the inflammatory potential of diet, dietary micronutrient insufficiencies, and diet quality between Black and White patients with HF.

Methods:
Patients with HF (n=361) who recorded food intake over 3-4 days were included (65% male, 62±12 years old). The inflammatory potential of diet (dietary inflammatory index [DII]), number of dietary micronutrient insufficiencies, and diet quality (Healthy Eating Index [HEI-2015]) were compared. Generalized linear regression models were used to evaluate the association between race and dietary indicators, controlling for age, sex, marital status, body mass index, financial status, and calories. For the regression model, the DII and number of dietary micronutrient deficiencies were dichotomized using median values due to the non-normal distribution.

Results:
Black patients with HF had more proinflammatory diets, a higher number of dietary micronutrient insufficiencies, and lower diet quality than White patients (1.39±2.15 vs 0.13± 2.40, P<.001; 6.5±3.9 vs 4.8±3.4, P<.001; and 49.8±14.4 vs 54.1±15.6, P=.021, respectively). Controlling for covariates, race was still associated with the proinflammatory potential of diet (P=.001) and number of dietary micronutrient deficiencies (P=.03) but not diet quality. Black patients were 2.7 times more likely to have more proinflammatory diet (95% CI: 1.50, 4.98) and 1.8 times more likely to have a higher number of dietary micronutrient insufficiency (95% CI: 1.06, 3.18).Conclusions: We found differences in dietary inflammatory potential and dietary micronutrient insufficiencies between Black and White patients with HF. Diet quality did not differ between Black and White patients after adjustment for covariates. Our findings suggest Black patients may be at higher risk for diets high in proinflammatory potential and micronutrient insufficiencies. In contrast, diet quality measured by HEI-2015 was less influenced by race than other factors controlled in the analysis.
Abstract 17387: The Ketone Body Beta-Hydroxybutyrate Attenuates Cardiomyocyte Hypertrophy Independent of BDH1-Mediated Oxidation
Authors: Matsuura Timothy R , Karwowski Mitja L , Naeem Fawaz , Lai Ling , Scott David , Westenbrink B D , Kelly Daniel P
Published: December 2023

Previously, we and others identified evidence for increased myocardial ketone body oxidation in failing mouse and human hearts and demonstrated that increased levels of beta-hydroxybutyrate (ßOHB), the most abundant ketone body, reduced pathologic cardiac remodeling in preclinical models of heart failure. To better understand how ßOHB prevents pathologic cardiac hypertrophy, we sought to determine whether: 1) ßOHB has direct effects on cardiomyocyte (CM) hypertrophy; and 2) if ßOHB oxidation is required for this effect. CMs were isolated from hearts of adult male C57BL/6 cardiac-specific beta-hydroxybutyrate dehydrogenase 1 knockout (csBDH1KO) mice and wildtype (WT) littermate controls. csBDH1KO CMs are unable to oxidize ßOHB given that BDH1 catalyzes the first step of R-ßOHB oxidation. CMs were cultured in media containing 5.5mM glucose ± 3mM R-ßOHB in the presence or absence of the hypertrophic agonist phenylephrine (PE, 100μM). CM width and length were quantified to assess hypertrophic growth. Stimulation with PE increased CM width:length ratio compared to glucose control by 31% and 33% in WT and BDH1KO CMs, respectively. Addition of R-ßOHB in the absence of PE had no effect on CM morphology, whereas R-ßOHB limited PE-induced increases in width:length ratio to 2% and 4% in WT and BDH1KO CMs, respectively (p<0.01 vs PE without R-ßOHB). In addition, PE-induced hypertrophy was prevented in WT CMs treated with S-ßOHB (this stereoisomer cannot be oxidized). To confirm that the cultured CMs utilized ßOHB, WT and BDH1KO CMs were cultured in media containing [U-
13
C] R-ßOHB. Stable isotope tracing showed significant fractional enrichment of citrate by R-ßOHB in WT CMs with limited enrichment in BDH1KO CMs (17.8% vs 4.5%, p=0.02). These findings support a role for ßOHB-mediated attenuation of cardiac hypertrophy through direct action on CMs via a mechanism independent of BDH1-mediated oxidation. Taken together with our previous results, these findings strongly suggest that ketone bodies improve heart failure by providing both oxidation-dependent (fuel source) and oxidation-independent as yet undefined cardioprotective mechanisms.
Abstract 17418: Daily Intake of Fruits and Vegetables Moderates the Effect of a Nutrition Intervention on Symptom Burden in Patients With Heart Failure
Authors: Kang JungHee , Lennie Terry , Biddle Martha J , Chung Misook L , Lin Chin-Yen , Wu Jia Rong
Published: December 2023

Introduction:
Patients with heart failure (HF) often remain symptomatic after optimization of medical treatment. Complementary interventions may reduce symptom burden. We conducted a 6-month randomized controlled trial of a nutrition intervention (NIHFT) to reduce fluid overload, oxidative stress, and inflammation, which are major pathologic pathways underlying HF symptoms.Aims: 1) To examine the effects of NIHFT on HF symptom burden (i.e., shortness of breath, edema, and fatigue); and 2) to determine if intake of fruits and vegetables, primary sources of antioxidants and anti-inflammatories, moderated the effect of the NIHFT on HF symptom burden.

Methods:
Patients with HF (n=116) with complete baseline data were included (61% male, 63±12 years old, 64% NYHA III/IV). Intervention group received 1) individualized educational intervention for sodium reduction that included promoting fruit and vegetable intake, 2) daily low sodium tomato or vegetable juice, and 3) omega-3 supplementation (1050 mg EPA, 150 mg DHA/capsule/day) for 6 months. Symptom burden was measured by the Memorial Symptom Assessment Scale-HF at baseline and 3 and 6-month. Daily intake of fruits and vegetables at baseline was dichotomized (≤1 vs ≥2 servings/day). A linear mixed-effect model was used.

Results:
There was no direct effect of the NIHFT on symptom burden. However, baseline intake of fruits and vegetables moderated the effect of the intervention on overall symptom burden scores (beta estimate= -4.67, SE=1.89, P=0.015). Reduction in symptom burden was greater among patients with lower baseline fruit and vegetable intake compared to those with higher intake. Among the subscales (i.e., frequency, severity, and distress) of overall symptom burden, frequency (beta estimate= -1.63, SE=0.66, P=0.014) and severity (beta estimate= -1.81, SE=0.61, P=0.004) were significantly moderated by the intake of fruits and vegetables.

Conclusions:
The findings indicate that the nutrition intervention was more effective in reducing symptom burden for patients with lower baseline intake of fruits and vegetables. This suggests that increased fruit and vegetable intake may further reduce HF symptom burden in patients on optimal medication therapy.
Abstract 17420: Enhanced Identification of Cardiac Wall Motion Abnormalities: An Externally Validated Deep Neural Network Approach Outperforms Expert and Quantitative Analysis of Electrocardiograms
Authors: Rogers Albert J , bhatia neal , Tooley James , Thakkar Vyom , XU JUSTIN , Ansari Rayan , Torres Jessica , Tung Jagteshwar , Alhusseini Mahmood , Clopton Paul L , Sameni Reza , Clifford Gari , Ashley Euan A , Perez Marco V , Zaharia Matei , Narayan Sanjiv M
Published: December 2023

Background:
Cardiac wall motion abnormalities (WMA) independently predict mortality and other adverse events beyond ejection fraction. Clinical screening relies on detection of ECG Q waves yet has poor predictive accuracy.

Hypothesis:
We hypothesized that ECG features beyond the Q wave could be identified by deep learning to improve WMA detection over standard ECG measurements.

Methods:
We collected ECGs and echocardiogram pairs (Panel A) in 35,210 unique patients who underwent both studies within 60 days at Stanford University. WMAs were determined by natural language processing (NLP) of clinical reports (Panel B). Five second ECG signals were extracted digitally and used to develop and test a DNN. For development, 80% of the pairs were used and 20% (N = 7042) were reserved for internal validation. We then tested the model performance on 2,338 echo/ECG pairs from Emory University. For comparison, qualitative physician statements from the ECG interpretation suggesting myocardial injury, ischemia, or infarct were labeled using NLP, and a logistic regression model was developed to include quantitative Q-wave measurements.

Results:
In the internal validation cohort (62.9±16.9 years, 47% female, 58% white), DNN of the ECG detected echocardiographic WMA with a c-statistic of 0.781 (CI: 0.764-0.798) which was superior to quantitative ECG Q wave measurement (0.632, CI: 0.605-0.661) or qualitative interpretation (0.595) (Panel C). Performance was not improved by incorporating demographic data. In the external cohort (61.9±16.0 years, 48% female, 48% white), the DNN AUC was 0.723 (CI:0.689-0.758).

Conclusion:
Deep learning improves detection of cardiac WMAs from the electrocardiogram in an externally validated model compared with standard ECG analysis. Application of this model may provide improved screening for regional myocardial injury. Further work will determine which features beyond the Q wave provide improved performance.
Abstract 17443: Wwox is a Critical Regulator of Pulmonary Artery Smooth Muscle Cell Homeostasis
Authors: Gomes Marta T , Chen Jiwang , Polidoro Rafael , Bai Yang , Prohaska Clare , Singla Sunit , Aldaz C. Marcelo M , Stearman Robert , Machado Roberto F
Published: December 2023

Introduction:
Pulmonary artery smooth muscle (PASMC) proliferation and apoptosis resistance are characteristic of pulmonary arterial hypertension (PAH). Expression loss of the tumor suppressor WW-domain containing oxidoreductase (WWOX) promotes cell survival and metabolic reprograming in cancer. We hypothesized that loss of WWOX expression in PASMC promotes pulmonary vascular remodeling by similar mechanisms.

Methods and Results:
mRNA and protein levels of WWOX are decreased in PASMC from patients with PAH, and in rat models of pulmonary hypertension (Sugen/ hypoxia and monocrotaline). PASMC-specific conditional Wwox knockout mice (WWOX-SMC KO) were treated with tamoxifen or vehicle for 5 days and exposed to 10% hypoxia for 4 weeks. WWOX-SMC KO animals developed worse hypoxia induced PH with increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodeling, compared to control animals. WWOX loss via siRNA decreased mRNA and protein levels of BMPRII, upregulated HIF 1alpha expression, increased hPASMC proliferation and migration. RNAseq revealed dysregulation in multiple pathways in WWOX-silenced hPASMCs, including cell-cycle regulation, TGF-β, mTOR and STAT3 signaling. Loss of WWOX showed decreased basal and maximal respiration, ATP production, reduced glycolytic capacity (40% in relation to control) and decreased mRNA expression of glycolytic enzymes (HK2, PFK1, PKM), generating 58% less lactate, and reduced mRNA expression of lactate dehydrogenase A. These cells exhibited increased mRNA and protein expression of glutaminase-1 and citrate lyase and had higher dependency on fatty acid oxidation and glutaminolysis compared to glucose, suggesting that these pathways are used when WWOX is suppressed. We also found mitochondrial hyperpolarization (JC-1 assay), decreased Sirtuin 3 expression, increased expression of acetylated manganese-superoxide dismutase, high production of reactive oxygen species and mitochondrial fission, indicating that loss of WWOX contributes to mitochondrial dysfunction.

Conclusion:
Loss of WWOX promotes cell cycle progression, proliferation, and metabolic reprogramming in PASMCs. Further studies are ongoing to better understand these effects.
Abstract 17467: Carvedilol Outperforms Metoprolol in Preventing Postoperative Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Abouzid Mohamed R , Eldahtoury Samar , Naccour Shereen , Anwar Junaid , Elshafei Shorouk , Vyas Ankit , Nwaukwa Chima
Published: December 2023

Introduction:
Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. Carvedilol is a nonselective beta-blocker with anti-inflammatory, antioxidant, and various cationic channel-blocking effects. This meta-analysis aims to compare the efficacy of carvedilol versus metoprolol in the prevention of POAF.

Methods:
We considered randomized controlled studies (RCTs) and retrospective studies that demonstrated the efficacy of carvedilol versus metoprolol in the prevention of POAF. Pooled data were analyzed using either the fixed-effect or random-effect model in Review Manager 5.3. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes.

Results:
A total of five RCTs and two retrospective studies (1000 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of mortality rate [Risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] as well as incidence of bradycardia [Risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [Risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001].

Conclusion:
In patients undergoing cardiac surgery, carvedilol has been shown to successfully minimize the occurrence of POAF. It appeared to be more effective than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, large-scale, well-designed randomized controlled trials are required.
Abstract 17474: Factors Affecting Cognitive Status in Patients With Intracranial Atherosclerosis After Surgical Revascularization: A Post Hoc Analysis of ERSIAS Phase-2 Performance Criterion (PC) Trial
Authors: Aguilera-Pena Maria Paula , Tusa Lavieri Miguel , Quintero Consuegra Miguel D , Song Shlee S , Schlick Konrad , Harris Jennifer , Simpkins Alexis , Chang Daniel , Nisson Peyton , Saver Jeffrey L , Gonzalez Nestor R
Published: December 2023

Introduction:
Cognitive decline affects a large proportion of patients with ischemic stroke. Intracranial atherosclerotic disease (ICAD) is a common stroke etiology associated with a high and prolonged risk of recurrence. In the ERSIAS phase-II trial, patients with symptomatic ICAD received revascularization with encephaloduroarteriosynangiosis (EDAS) plus intensive medical management (IMM) of stroke risk factors. We present a subgroup analysis of features affecting cognitive outcomes.

Hypothesis:
To evaluate the factors contributing to cognitive decline in patients who underwent revascularization for symptomatic ICAD.

Methods:
ERSIAS patients without aphasia that completed at least one year of follow-up were included. Cognitive status was evaluated using MoCA at baseline and each follow-up and classified as improved/preserved vs. worsened. Classification and Regression Tree Analysis (CART) was used to identify factors associated with changes in cognitive function. Factors considered were age, sex, stenosis vs. occlusion, baseline-mRS, good collateralization and compliance with diabetes (DM) hypertension (HTN), and hyperlipidemia (HLD) treatments.

Results:
In ERSIAS, the mean MoCA at baseline was 22.4 (SD 4.9), and 23.9 (SD 4.9) at one-year follow-up in the complete population. Thirty-nine patients were included in this analysis. Median age was 46 (IQR 37.0-56.0), and 27 (69.2%) were female. MoCA improved or remained stable in 33 (84.6%) patients and declined in 6 (15.4%). CART analysis revealed that the most relevant factors for improved MoCA were compliance with DM treatment (94.5%(yes) vs.74.2%(no) p=0.02) HLD treatment (83.3% (yes) 60.5%(no) p=0.2) and stenosis 99.1% vs. occlusion 80.9%, p=0.6 Other factors where not found to be contributory.

Conclusions:
Compliance with DM treatment is a significant predictor of cognitive preservation in symptomatic ICAD patients. Our findings emphasize the importance of IMM of stroke risk factors in patients with intracranial atherosclerosis, even after surgical revascularization.
Abstract 17494: The Incremental Risk Prediction of Cardiac CTA-Derived Quantitative Atherosclerosis in the International Advance Registry
Authors: Chinnaiyan Kavitha M , Guez Ilana , Sussman Vida , Patel Manesh R , Norgaard Bjarne L , Fairbairn Timothy , Koen Nieman , koweek lynne , Pontone Gianluca , Sand Neils P , Sonck Jeroen , Rabbat Mark , Mullen Sarah , Ng Nicholas , De Bruyne Bernard , Rogers Campbell , Matsuo Hitoshi , Bax Jeroen J , Leipsic Jonathon
Published: December 2023

Background:
We sought to assess the incremental prognostic utility of AI-enabled quantitative coronary plaque assessment (AI-QCPA) beyond stenosis severity and FFR
CT
, for the prediction of late revascularization and MACE in the large prospective international ADVANCE registry.

Methods:
4737 participants were submitted for AI-QCPA evaluation. Total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV), and low attenuated plaque volume (LAPV) were quantified. In addition, total percent plaque volume (TPAV) and its components were calculated (PV/Vessel Volume * 100). Demographics, stenosis severity, lowest FFR
CT
, and Delta FFR
CT
were also recorded. To explore the relationship between plaque measures and MACE (death, myocardial infarction, and unplanned hospitalization leading to revascularization) and late revascularization (>90 days) we performed Kaplan Meier event free outcomes analyses following adjustments for stenosis severity, FFR
CT
and Delta FFR
CT
.

Results:
AI-QCPA was available in 4430 subjects. Mean (SD) TPV was 542.4 ± 522.5 mm
3
. Optimal cutpoints of plaque metrics were predictive of MACE and/or late revascularization when adjusted-TPV (HR- 1.45 CI- 1.06-1.98; P=0.02); CPV (HR- 1.65 CI- 1.21- 2.26; p=0.002); NCPV (HR 1.43 CI- 1.02-1.99; P=0.04) and LAPV (HR- 2.23 CI 1.62-3.07; P=0.03 . Stronger risk prediction was achieved by plaque measures adjusted for vessel volume: TPAV (HR 1.92 CI 1.40- 2.64 P<0.001). This incremental risk discrimination of quantitative plaque measures remained significant as a predictor of MACE alone- TPV- (HR 1.84 CI 1.02- 3.29 P=0.04) TPAV (HR 3.33 CI- 1.85- 6.02 P<0.0001) (Figure 1).

Conclusions:
In this large prospective international registry, AI-QCPA provided incremental risk discrimination for MACE and late revascularization beyond stenosis severity and FFR
CT
.
Abstract 17501: Initial Experience With a Novel Transcatheter Aortic Valve With Open-Cell Design and Staged Delivery for Challenging Anatomies in a Developing Country
Authors: Marino Marcos Antônio , Marino Roberto Luiz , Marino Bárbara C , Rabelo Walter , Mariano de Azevedo Frota Hugo A , Andrade Evandro Vitor , Vasconcellos Alexandre V , Couto Luis Eduardo D , De Paula Jessica , Bernardes Rodrigo C , Reis Filho Fernando Antônio R , Cobucci Santana Alexandre Henrique , Nascimento Bruno R
Published: December 2023

Introduction:
Overcoming challenges of transcatheter aortic valve (TAVI) implantation, as coronary access, conduction disturbances and paravalvular leak are goals of device development. We aimed to describe the initial experience with a recently-approved self-expandable bioprosthetic valve, with supravalvular leaflets, a novel open-cell design and 2-stage deployment, in terms of efficacy and safety.

Methods:
Consecutive patients with aortic valve (AV) stenosis and indication for TAVI with favorable anatomy for self-expandable prostheses were prospectively enrolled in a high-volume center in Belo Horizonte, Brazil. Demographic, clinical and procedural data were collected in an online dedicated database (Coreware, RIBAC). Echocardiographic and CT-angio measurements were performed by 2 experts with proprietary software (Phillips Heart Navigator). Outcomes were prospectively collected.

Results:
At total, 23 patients eligible for the Acurate Neo/Neo2 TAVI were enrolled, being 15 men, mean age of 82±6 years (69 - 93). Hypertension was present in 20, diabetes in 8 and dyslipidemia in 17, and all were severely symptomatic, being 20 in functional class 3. The STS-score (morbi-mortality) was high: 19±6%. The mean AV area on echo was 0.7±0.2 cm
2
, with mean gradient of 44±15 mmHg. In CT-angio, the median calcium score was 2284, mean annular perimeter was 72±5 mm, and the height of the right and left coronary ostia were 15.2±2.6 mm and 11.9±3.2 mm (<10 mm in 5 cases). All implants were transfemoral (14F) and with general anesthesia, given the high-risk profile. Pre-dilation was performed in 20 (91%) and the TAVI was deployed without repositioning in all cases, with no coronary compromise. Post-dilation was required in 13 cases, being 11 due to mild and 2 due to moderate paravalvular leak: all regressed to trivial. Vascular complications requiring surgery occurred in 1 case, and 1 (4%) patient underwent permanent pacing. All patients were discharged home, with a mean AV gradient of 9.7±3.7 mmHg.

Conclusion:
The initial experience in Brazil with the novel Acurate Neo/Neo2 prosthesis was promising, with high success rates in challenging anatomical scenarios, and low rates of pacemaker implantation and no occurrence of coronary obstruction or significant leak.
Abstract 17509: Gender-Specific Differences in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Morland Thomas , Abbas Mostafa , Shuhaiber Jeffrey , Hall Eric S , Kirchner H Lester , El-Manzalawy Yasser
Published: December 2023

Background:
Several studies suggested that females undergoing coronary artery bypass grafting (CABG) have poorer outcomes than males. However, we noted contradicting findings regarding short and long-term mortalities among females. Our aim is to assess gender-specific differences in pre and post -operative CABG risk factors and outcomes.

Methods:
Our cohort included 7,687 adult patients who underwent CABG surgery between 2006 and 2022 in a large rural healthcare system. Patients were grouped by gender and continuous variables were summarized using median and inter-quartile range. Appropriate statistical tests were conducted to assess differences.

Results:
There were 1827 (23.8%) females and 5860 (76.2%) males. Females were slightly older ((68, 60.5, 75) vs (67, 65, 73), p<0.0001), with higher total number of Elixhauser comorbidities ((6, 3, 8) vs (4, 3, 7), p<0.0001), higher cha2ds2vasc scores ((4, 3, 5) vs (3, 2, 4), p<0.0001) and higher prevalence of stroke history (12.4% vs 10.3%, p=0.013). Analysis of risk factors used for computing the Society of Thoracic (STS) scores revealed several significant differences (with p<0.001) between females and males including sleep apnea (12.1% vs 15.7%), diabetes (52.7% vs 43.4%), depression (25.5% vs 13.9%), and BMI ((31.6, 14.4, 35.5) vs (28.8, 25.8, 33.7)). Compared to males, females had greater need for blood transfusions (49.8% vs 33.6%), prolonged post-operative pulmonary ventilation (33.8% vs 24.4%), mediastinal drainage (13.4% vs 6.4%) and more frequent acute cardiac arrests (7.2% vs 4.8%). In addition females had higher 30-day mortality (0.93% vs 0.84%, p=0.014), 1-year mortality (4.2% vs 2.9%, p=0.0003), 1-year incident stroke (2.2% vs 1.5%, p=0.05), longer hospital length of stay (LoS) in hours ((143.4, 116.9, 191.6) vs (120.7, 96.9, 167.2), p<0.0001), ICU LOS in hours ((96, 48.8, 143.9) vs (77.9, 39.4, 120), p<0.0001), and duration from discharge to all-time mortality in days ((1513, 523.5, 2723.5) vs (1740, 622, 2921), p=0.008).

Conclusions:
Female gender is linked to several pre-operative and post-operative risk factors and are at greater risk of adverse outcomes following CABG surgery. Further work is needed to understand the causes of these discrepancies and to limit their effect on outcomes.
Abstract 17551: Mapping the Interactome of FLNC in Restrictive Cardiomyopathy
Authors: Wang Bryan , Zhang Xiaokan , Luo Lori , Morsink Margaretha , Rao Jenny , Vunjak-Novakovic Gordana , Fine Barry
Published: December 2023

Introduction:
Filamin C (FLNC) is an actin crosslinking protein that organizes structural components of the sarcomere and signal transduction complexes. Human mutations in FLNC have been linked to dilated, hypertrophic and restrictive cardiomyopathies. The mechanism connecting mutations in FLNC to sarcomeric impairment remains undefined. We recently reported the ability to model FLNC cardiomyopathy using induced pluripotent stem cell (iPSC) derived engineered heart tissue. Here, we employ a knock-in approach to epitope tag endogenous alleles in iPSC derived cardiomyocytes to explore FLNC genotype-interactome relationships using affinity purification mass spectrometry.

Methods:
An iPSC line was generated from a patient with restrictive cardiomyopathy caused by an insertion deletion mutation in the ROD2 domain
FLNC
(c.7416_7418delGAA, p.Glu2472_Asn2473delinAsp). CRISPR-Cas9 was used to establish a corrected cell line as a wild type control. 3X-Flag motif was introduced to the N terminus of
FLNC
using CRISPR-Cas9. iPSCs were then differentiated into cardiomyocytes using standard techniques. Affinity purification mass spectrometry (AP-MS) was performed using the Flag epitope. Interaction data was analyzed using Perseus software. Gene ontology (GO) enrichment analysis was performed using ToppFun.

Results:
3X-Flag insertion was confirmed using genomic sequencing. AP-MS identified 281 high confidence interactors of mutant FLNC and 208 interactors of wild type FLNC (FDR 0.01, log2FC >1.5) when compared to IgG controls. Interestingly, 161 proteins were shared between the two genotypes. These were enriched in mitochondrial ribosomal proteins and phosphorylase kinase subunits, potentially revealing an unknown role of FLNC in mitochondria translation and metabolism. Thirty-three proteins were significantly differentially bound to mutant FLNC protein, including tropomyosin 4, caldesmon 1, and filamin A (FDR <0.05, log2FC>1). GO analysis of these proteins revealed enrichment of actin cytoskeleton elements, muscle contraction, and muscle system processes.

Conclusions:
Human mutations in FLNC lead to disruption of key protein interactions, revealing a potential mechanism for disease pathogenesis in FLNC cardiomyopathy.
Abstract 17558: Using Patient Reported Outcomes to Predict Patency and Revascularization in Peripheral Artery Disease: A Zilver PTX Sub-Analysis
Authors: Romain Gaelle , Hanna Jonathan , Cleman Jacob , Smolderen Kim G , Mena-Hurtado Carlos
Published: December 2023

Introduction:
Health status measured by patient reported outcomes (PROs) can predict future major cardiovascular events in patients with peripheral artery disease (PAD). It is unclear, however, whether health status outcomes can also predict revascularization success.

Methods:
We preformed sub-analysis of the Zilver PTX trial (multinational randomized trial and US single arm) including patients with above-the-knee symptomatic femoropopliteal disease and receiving paclitaxel-eluting stents (Zilver PTX) between 2005-August 2008. We examined the association of patients’ pre-procedural health status measured by EQ-5D-3L Index (EQ-5D), a validated PROs instrument (Value < 0 means health status worse than death, 0: death and 1: full health) and the 12-month treatment durability outcomes measured as primary patency and target lesion revascularization (TLR). Point-biserial correlations were calculated between EQ-5D and outcomes. The 12-month cumulative incidence of patency and TLR was constructed using Kaplan-Meier curves and compared by EQ-5D quartile using Log-rank test.

Results:
The Zilver PTX arm included 704 patients with a mean age of 68±10 years, 26% women, and 3% Black/African American. The mean EQ-5D pre-procedural Index was 0.79±0.12 and 0.87±0.15 at 12 months. Correlations between the pre-procedural EQ-5D and patency and TLR were, respectively, -0.006 (P=0.82) and 0.034 (P=0.31). In the overall cohort, the cumulative incidence of patency loss was 17% 95%CI 15-21 and of TLR was 9% 95%CI 7-11. There was no significant difference in the 12-month risk of either patency loss or TLR across EQ-5D quartiles (P=0.93 and P=0.85) (Figure).

Conclusions:
Pre-procedural generic health status are not predictive of post procedural endpoints of revascularization success such as patency and TLR in patients receiving Zilver PTX, underscoring the need of adding these complementary measures to evaluate the full scope of success following revascularization in PAD.
Abstract 17563: Serial ABPM, Antihypertensive Drug Treatment, and Pregnancy Outcomes in Women With Hypertension Found Early During Pregnancy
Authors: Wojciechowska Ewa M , Gryglas Piotr
Published: December 2023

Introduction:
Few data are available on serial ambulatory blood pressure monitoring (ABPM) throughout pregnancyand antihypertensive drug treatment required for good blood pressure (BP) control in hypertensivepregnant women.

Hypothesis:
Evaluation of BP control, antihypertensive drug treatment intensity, and pregnancy outcomes in patients with hypertension (HTN) found early during pregnancy.

Methods:
We studied 49 consecutive pregnant patients (mean age 33.4±4.8 years, BMI before pregnancy24.5±3.7 kg/m2) referred for office HTN found early during pregnancy who gave birth to 50 children (1 twin pregnancy) in 2011-2015. Gestational HTN was previouslydiagnosed in 39 women, and 9 women had a history of previous miscarriage or stillbirth, with multipleprevious pregnancies lost in some patients. ABPM was repeated at 5-10-15-20-25-30-33-35-37 weeksof pregnancy. We calculated overall antihypertensive treatment intensity in standard daily drug doses per patient (standard doses: labetalol 200 mg, methyldopa 750 mg, metoprolol 50 mg, nifedipine 20mg, verapamil 120 mg). Statistical analysis was performed using ANOVA.

Results:
All children were born alive (24 vaginal delivery, 26 cesarean section) and are well at follow-up.Gestational age was 38.0±2.5 (range 29-40) weeks, and birth weight was 3215±653g (range 955-4200). Preeclampsia/eclampsia occurred in 10/3 patients. Four patients had normal BP values by ABPM throughout pregnancy and did not receive antihypertensive drugs. Most patients were treatedwith labetalol and methyldopa. Throughout pregnancy, BP remainedwell controlled (24h mean SBP/DBP 120.3-126.0/75.3-77.1 mmHg), the number of treated patientsincreased from 25 at 5 weeks to 42 at 25-35 weeks, and the average number of daily antihypertensivedrug doses in treated pts increased from 1.82 at 5 weeks to 2.98 at 37 weeks.

Conclusions:
Serial ABPM-guided antihypertensive drug treatment started early during pregnancywas associated with favorable outcomes. The number of patients requiring treatment increased throughout the pregnancy. No physiological BP fall atthe end of 1 st trimester was observed. Our findings help estimate the expected treatment intensity required in pregnant patients with preexisting hypertension.
Abstract 17573: Reliability of Non-Invasive Arterial Pressure Monitoring via ClearSight System™ During Cardiac Ablation and Transvenous Pacemaker Lead Removal
Authors: Thompson Colton D , Vrtikapa Dejan , Olech Jeffrey , Wright Jennifer , Dollerschell John
Published: December 2023

Background:
Invasive arterial catheter (IAC) placement can lead to hematoma, vessel occlusion, pain and & procedure delay. The ClearSight System™ (CSS) is a non-invasive blood pressure (NIBP) device that measures beat-to-beat arterial pressures (AP) via a finger cuff. The validity of CSS during cardiac ablation & transvenous pacemaker lead removal has not been described. Therefore, we performed a single center observational study to validate AP monitoring by CSS compared to IAC in such patients (pts).

Methods:
Pts undergoing cardiac ablation or lead removal from June-November 2022 were included. AP was simultaneously measured via CSS & IAC. Measurements were compared using Bland-Altman analysis. Acceptable bias & precision (standard deviation) were defined as <5 mm Hg & <8 mm Hg respectively based on Association for the Advancement of Medical Instrumentation standards. An exploratory analysis on impacts of BMI, sex, & type of procedure on validity of CSS was also assessed.

Results:
Paired AP measurements were available for 61 pts (6967 paired measurements). Median age was 67 (IQR 60.5-73.5), BMI 29.2 (IQR 26.1-37.1) & 31% of pts were female. Procedures included atrial fibrillation ablation (n=32), SVT ablation (n=13), lead extraction (n=9), & VT ablation (n=7). Bland-Altman analysis comparing AP via CSS vs IAC showed that the CSS overestimated systolic arterial pressure (SAP) & underestimated both diastolic arterial pressure (DAP) & mean arterial pressure (MAP). Mean bias was 4.2 ± 12.9 (SAP), -4.99 ± 9.2 (DAP) & -2.4 ± 11.78 (MAP) (Figure 1). Exploratory analysis showed that CSS was not interchangeable with IAC monitoring regardless of subgroup (MAP male sex -1.9 ± 11.1; BMI ≥30 -2.7 ± 9.7; ablation -1.8 ± 12.2).

Conclusion:
Continuous NIBP monitoring via CSS was not interchangeable with IAC monitoring in pts undergoing cardiac ablation & lead extraction.
Abstract 17593: Betel Quid Addiction Causing Monomorphic Ventricular Tachycardia
Authors: Clark Cali , Miller Shane , Wilberding Justin
Published: December 2023

A 44-year-old woman presented to the emergency room due to worsening shortness of breath over the past few days with accompanying dizziness, cough, and fever. Her history was significant for asthma, obstructive sleep apnea, and hypertension. Upon arrival, she was noted to be hypoxic on room air and required supplemental oxygen. Physical exam showed extensive pitting edema in the lower extremities and crackles in bilateral lung fields. Chest radiograph revealed an enlarged cardiac silhouette and increased interstitial infiltrates consistent with pulmonary edema. While in the emergency department she was noted to have frequent episodes of asymptomatic non-sustained monomorphic ventricular tachycardia. Further questioning revealed the patient had been using betel quid daily for over 20 years to improve her mood and energy levels. She had attempted to quit in the past but was unable to do so. Echocardiogram was performed which showed preserved left ventricular function and severely dilated right ventricle. BNP was elevated at 1930 pg/mL. Due to her ventricular arrhythmias and cardiomyopathy, coronary angiography was performed; this was negative for epicardial coronary artery obstruction. Case was discussed with electrophysiology who determined the arrhythmias were likely caused by the extensive betel quid consumption. She was placed on beta-blockers and betel quid cessation was strongly recommended.

Betel quid is a chewing product made from of areca nut, betel leaf, slaked lime, with or without tobacco. It is commonly used in the tropical Pacific, Asia, and parts of East Africa, and is the fourth most widely consumed addictive substances in the world due to its ability to increase alertness and produce mild euphoria. Adverse effects of betel quid include tachycardia, hyperlipidemia, metabolic syndrome, hepatotoxicity, and it is a known carcinogen. The active compound is arecoline, which acts as a parasympathomimetic on muscarinic and cholinergic receptors, increasing the central sympathetic response and producing tachycardia. Betel quid has been shown to produce ventricular arrhythmias in patients with underlying cardiomyopathy, which is likely what occurred in our patient. Betel quid cessation therefore advised in these patients.