bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15010: Relationship Between Low Diastolic Blood Pressure, All-Cause Mortality and Cardiovascular Outcomes: A Meta-Analysis
Authors: Usman Muhammad Shariq , Siddiqi Tariq J , Siddiqui Amna , Khan Laibah , Shabbir Aisha , Salman Ali , Hall Michael E , Taffet George E
Published: December 2023

Background:
Reduction of diastolic blood pressure (DBP) below 70mmHg may decrease perfusion to the heart and worsen cardiovascular (CV) outcomes. However, studies assessing the association between low DBP and clinical outcomes have yielded inconsistent results.

Aim:
To meta-analyze the association between low DBP and CV outcomes.

Methods:
We searched the MEDLINE, Scopus, and Cochrane CENTRAL databases up until December 2022 for studies reporting the risk of all-cause mortality (ACM) or CV outcomes in patients with low versus normal DBP. Patients with a DBP of 70-80mmHg were considered the control and were compared to those with a DBP of 60-69mmHg and <60mmHg. Outcomes of interest were all-cause mortality (ACM), major adverse cardiac events (MACE), myocardial infarction (MI), and ischemic stroke. Subgroup analysis was performed to assess whether pre-existing CV disease was an effect modifier. Findings from studies were pooled using a random-effects model to derive hazard ratios (HRs) and 95% confidence intervals.

Results:
Ten studies (n = 1,998,223 participants) met the eligibility criteria. A mean achieved DBP<60mmHg was associated with a significantly increased risk of ACM (HR: 1.48 [1.26, 1.74]; P < 0.001) compared with a mean achieved DBP of 70-80mmHg (
Fig. 1a
). This association was significantly stronger in patients with pre-existing CV disease (P-interaction < 0.001). A DBP<60mmHg was also associated with a higher risk of MACE (HR: 1.84 [1.28, 2.65]; P < 0.001) and MI (HR: 1.49 [1.13, 1.97]; P < 0.001). However, a DBP<60mmHg had no significant association with ischemic stroke. A mean achieved DBP 60-69mmHg was associated with a significantly increased risk of ACM (HR: 1.11 [1.03, 1.20]; P < 0.001;
Fig. 1b
), but not MACE, MI, or ischemic stroke.

Conclusion:
Reduction of DBP below 70mmHg, particularly below 60mmHg, is associated with an increased risk of mortality. This association is stronger in patients with pre-existing CV disease.
Abstract 15025: Impact of Type of Transcatheter Heart Valve and Anatomic Features on Complexity of Percutaneous Coronary Intervention in Patients After Transcatheter Aortic Valve Replacement
Authors: Takahashi Norihito , Doi Shinichiro , Dohi Tomotaka , Hirohisa Endo , Nishiyama Hiroki , Okai Iwao , Miyazaki Sakiko , Iwata Hiroshi , Fujimoto Shinichiro , Okazaki Shinya , Minoru Tabata , Minamino Tohru
Published: December 2023

Introduction:
Approximately half of the patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) present with concomitant coronary artery disease (CAD). Percutaneous coronary intervention (PCI) after TAVR is gaining increasing importance. Consequently, we investigated the factors that influence PCI procedures in patients following TAVR.

Methods:
We included consecutive 633 patients with severe aortic stenosis who underwent TAVR at our institution from 2016-2022. The primary endpoint was the time from puncture to initial coronary angiography.

Results:
The median age was 84 (81 - 87) years old, 39% were male, and 173 (27.3%) had concomitant coronary artery disease. Of these, 39 (22.2%) were treated conservatively, 22 (12.5%) underwent coronary artery bypass and TAVR, 64 (36.5%) underwent PCI before TAVR, and 46 (26.2%) underwent PCI after TAVR. The success rate of PCI after TAVR was 100% for both types of valves. The median initial angiography time from puncture was 16.2 minutes (10.6 - 29.1), significantly longer in the Self-expandable valve (SEV) group [22.0 minutes (14.1 - 59.2)] compared to the Balloon-expandable (BEV) group [14.9 minutes (8.1 - 21.1)] (p = 0.026). PCI to the right coronary artery [29.0 min (17.2 - 49.5)] took significantly longer than PCI to the left coronary artery [14.0 min (8.0 - 18.1)] (p = 0.001). Conversely, there was no significant association with CT measurements such as aortic angle, annulus area, coronary height, or valve size, and transcatheter heart valve size (p > 0.05). Factors that predicted difficulty in engaging coronary arteries (>30 min from puncture to first contrast) were SEV [odds ratio 6.4, 95% confidence interval (1.2 - 38.2), p = 0.024], RCA [odds ratio 6.0, 95% confidence interval (1.3 - 33.4), p = 0.020].

Conclusions:
Despite the high completion rate of PCI after TAVR, the use of SEV and the approach to the right coronary artery can pose challenges.
Abstract 15047: The Probability of miRNA Derived From Extracellular Vesicles as Functional Biomarkers for Patients With Lower Extremity Artery Disease
Authors: Kuriyama Naoya , Kikuchi Shinsuke , Yoshioka Yusuke , Matsuzaki Juntaro , Azuma Nobuyoshi , Ochiya Takahiro
Published: December 2023

Introduction:
Lower extremity artery disease (LEAD) is a progressive and systematic manifestation of atherosclerosis. In LEAD, multiple arterial beds are affected increasing the possibility of death due to coronary artery disease (CAD) and cerebrovascular disease (CVD). We have identified functional biomarkers that can be used to predict clinical outcomes in patients with LEAD by analyzing miRNAs contained in the extracellular vesicles (EVs).

Methods:
A total of 146 patients with diabetes and without end-stage renal disease were enrolled as research subjects between 2019 and 2021. Among them, 118 had LEAD, including 6 asymptomatic cases, 43 cases of claudication, and 69 cases of chronic limb-threatening ischemia (CLTI). The remaining 28 cases were in the Control group, who were systematically screened for atherosclerotic lesions by radiological modalities. We performed miRNA sequencing using the EV-derived miRNAs from patients’ serum. We developed machine learning based models to diagnose LEAD, CLTI, CAD, and CVD. We used Cox models to identify miRNAs associated with the patency rate at the reconstruction site, amputation-free survival (AFS), and major cardiovascular events (MACE).

Results:
The area under curve (AUC) of the diagnostic models for LEAD, CLTI, CAD, and CVD for the training data were 0.82, 1.00, 1.00, and 1.00, respectively, and for the test data were 0.68, 0.85, 0.71, and 0.51, respectively. The diagnostic model for CLTI showed the highest generalization performance among these models. We performed pathway analysis for miRNAs with fold change > 2 in CLTI using DIANA-miRPath v3.0, which revealed enrichment of proteoglycans in cancer, Wnt signaling, and TGF-beta signaling pathways.We identified 62 miRNAs as significant risk factors affecting the patency. The group with has-miR-6850-3p above the median (78.8%) had significantly higher one-year patency rate compared to the group with has-miR-6850-3p below the median (59.5%) (p = 0.03). In addition, we identified 6 and 4 miRNAs as risk factors related to AFS and MACE, respectively.

Conclusions:
EV miRNAs have high potential as biomarkers for predicting prognosis, treatment outcome, and other atherosclerotic lesion associated with LEAD in the diabetic patients.
Abstract 15055: Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicenter Cohort Study
Authors: Mohr Katharina , Mildenberger Philipp , Valerio Luca , Kaier Klaus , Christodoulou Konstantinos , Farmakis Ioannis T , Barco Stefano , Schmidtmann Irene , Binder Harald , Konstantinides Stavros V
Published: December 2023

Introduction:
Analysis of administrative data has helped to determine hospitalization costs related to acute pulmonary embolism (PE) in several countries, but estimating long-term costs of patient care after discharge is a more challenging task.

Aims:
To determine the direct annual costs related to the care of PE survivors based on data from a longitudinal cohort study performed at 17 German large-volume hospitals.

Methods:
The Follow-up of Acute Pulmonary Embolism (FOCUS) study enrolled unselected patients with acute PE. In addition to a structured ambulatory follow-up (FU) program
(Figure)
, we prospectively recorded duration and type of anticoagulation and the main and accompanying causes of all rehospitalizations during the first year of FU. Annual per-patient costs of post-PE care were calculated in 2022 euro (є) and converted to US$ adjusting for purchase parity power.

Results:
A total of 1,017 patients (45% women; median age 64 years [IQR, 52-74]) were included. Average costs of scheduled ambulatory FU visits and tests were estimated at є136.37 ($189.40) per patient; costs of oral anticoagulation after hospital discharge for the index event amounted to є827.72 ($1,149.61). The annual all-cause hospitalization rate was 31.96% (95% CI, 28.0-35.91%); the
Table
shows the primary indications and mean hospital costs (overall, and per indication). Of the є1,104.48 ($1,534.0) average rehospitalization costs per patient, 8.9% were related to recurrent thrombosis/PE or bleeding.

Conclusions:
Our results, derived from the population of a prospective multicenter study, help to dissect the direct annual costs of chronic post-PE care and may inform ambulatory care programs.
Abstract 15063: Incidence and Risk Factors for Heart Failure in 20 000 Newly Diagnosed Diabetes Patients
Authors: Lejonberg Carl , Czuba Tomasz , Bennet Louise , Melander Olle , Gomez Maria F , Ahlqvist Emma , Smith Gustav
Published: December 2023

Introduction:
Heart Failure (HF) is a diabetes complication causing high mortality and morbidity but has received relatively limited attention compared to other complications such as acute myocardial infarction (AMI). Substantial residual HF risk remains after achieving current treatment targets, suggesting important additional pathophysiological mechanisms beyond conventional risk factors.

Aim:
to study the incidence and risk factors for HF in newly diagnosed diabetes patients.

Methods:
We used a contemporary, regional inception cohort (n=19,938) from Scania County in Sweden, to study the incidence and risk factors for HF from initial diabetes diagnosis. Biochemical and questionnaire data were collected within 1 year from initial diagnosis in newly diagnosed diabetes patients (>90% participation rate). We combined baseline data with information on incident HF and AMI diagnoses from a nationwide patient register, and applied Cox-regression models for analysis.

Results:
A total of 819 patients (4%) had been diagnosed with HF before diabetes diagnosis (median 3 years earlier) and 1245 (6%) with AMI. The cumulative incidence of HF in patients free from HF at diabetes diagnosis was 5%, similar to AMI (3%), during up to 13 years follow-up (median 5 years). Of patients with incident HF, 27% had a prior AMI. No type 1 diabetes (T1D) patient had incident HF, while HF risk was similar in type 2 diabetes, latent autoimmune diabetes in adults (LADA) and secondary diabetes. In non-T1D diabetes patients, male sex (HR 1.52) and higher age at onset (HR 1.08), BMI (HR 1.04), and insulin resistance (HR 1.17) were independently associated with higher incidence of all-cause HF and HF without prior AMI (p<0.05). Baseline fasting glucose, HbA1c and autoantibodies were not associated with HF.

Conclusions:
Our findings demonstrate high incidence of HF over the decade after initial diabetes diagnosis, comparable to AMI. We further identify insulin resistance, but not hyperglycemia or autoantibodies, as risk factor for HF.
Abstract 15078: Atrial and Brain Natriuretic Peptides Expression and Release in Pulmonary Hypertension
Authors: Van Wezenbeek Jessie , Llucia-Valldeperas Aida , Smal rowan , Bekedam Fjodor , De Man Frances S
Published: December 2023

Introduction:
Precapillary pulmonary hypertension (PH) is characterized by progressive overload for the right ventricle and right heart failure (RHF). N-terminal Brain Natriuretic Peptides (NTproBNP) and Atrial Natriuretic Peptides (ANP) are secreted from cardiomyocytes upon stretch. NTproBNP is used as biomarker for RHF. Aim: To study the association between ANP and NTproBNP and pressure overload in blood, right heart tissue and induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) from PH-patients.

Methods:
We analyzed NTproBNP in 344 PH-patients, 9 controls, and in 9 PH-patients before and 6-months after pulmonary endarterectomy (PEA). We measured NPPA and NPPB gene expression on end-stage human right ventricular (RV) and right atrial (RA) samples from 8 PH-patients and 5 controls. In addition, we performed immunofluoresence staining for ANP and BNP on RA tissue (N=4) and RV tissue (N=10) in PH and controls (N=5). iPSC-CMs from 1 male and 1 female PH-patients were stretched for 24h at 1Hz and 10% on the Flexcell FX-6000 system, and NTproBNP release was measured on static and stretched iPSC-CMs. NTproBNP levels were measured through ECLIA.

Results:
NTproBNP serum levels were elevated in PH-patients versus controls (918 vs 25 pg/mL, Fig1A). Pressure unloading in CTEPH patients did not result in a decrease in NTproBNP (Fig1B). In RV tissue of PH-patients NPPA expression was upregulated, but NPPB was not (Fig1C). ANP and BNP content was higher in RA and RV tissue of PH-patients (Fig1D-E). Finally, ~5x higher NTproBNP was released from male vs female iPSC-CMs under static conditions and after mechanical stretch (Fig1F).

Conclusions:
ANP and BNP showed important differences at gene and protein levels in relation to pressure overload. To confirm current results, further analyses on atrial and ventricular iPSC-CMs will be performed, in addition to mid-range proANP measurements in patients’ blood and iPSC-CMs conditioned medium.
Abstract 15093: Serum Apolipoprotein-A2 Levels Are a Stronger Predictor of the Residual Cardiovascular Event Risk After Percutaneous Coronary Intervention
Authors: Akiyama Takumi , Ikegami Ryutaro , Kubota Naoki , Takano Toshiki , Yoneyama Shintaro , Okubo Takeshi , Hoyano Makoto , Ozaki Kazuyuki , Inomata Takayuki
Published: December 2023

Introduction and Aim:
Apolipoprotein-A2 (apoA2) is the second major apolipoprotein that constitutes high-density lipoprotein cholesterol (HDL-C) particles, following apolipoprotein-A1 (apoA1). HDL-C can be divided into two main subfractions: those containing both apoA1 and apoA2, and those containing only apoA1. It is believed that HDL-C particles with apoA2 exhibit superior functionality in lipid metabolism compared to those without apoA2. However, the clinical impact of apoA2 on future cardiovascular events in patients who have undergone percutaneous coronary intervention (PCI) remains unclear. The aim of our study is to test the hypothesis that apoA2 would be a stronger predictor of residual cardiovascular risk compared to other apolipoproteins in the statin era.

Methods:
We examined 638 patients who underwent PCI with a second-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoproteins measured between 2016 and 2021 (median follow-up period of 17.7 months). The patients were divided into two groups based on the median serum apoA2 values. We assessed the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, ischemic stroke, exacerbation of heart failure, or target vessel revascularization.

Results:
A total of 563 patients (88%) received statin treatment, and the median serum low-density lipoprotein cholesterol was 93 mg/dL. A total of 138 patients (21.6%) experienced MACEs, and Kaplan-Meier analysis revealed that the lower apoA2 group had a significantly higher incidence of MACEs compared to the higher apoA2 group (23.6% vs. 19.7%, p=0.036). However, the other apolipoproteins, including apolipoprotein-A1, B, C2, C3, or E, showed no significant difference in MACEs. Multivariate Cox hazard analysis indicated that apoA2 was an independent predictor of MACEs (hazard ratio 1.51; 95% confidence interval 1.06-2.14, p = 0.022). Furthermore, apoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (ρ= -0.48, p<0.0001).

Conclusions:
Serum apoA2 level may be the strongest predictor of residual cardiovascular event risk after PCI among apolipoproteins.
Abstract 15106: Echocardiography versus Cardiac Magnetic Resonance-Quantification of Right Ventricular Function to Stratify the Risk of Appropriate Defibrillator Therapy
Authors: Chiba Toshinori , Kajiyama Takatsugu , Kondo Yusuke , Nakano Masahiro , Ito Ryo , RYUZAKI SATOKO , Yoshino Yutaka , Komai Yuya , Takanashi Yukiko , Kobayashi Yoshio
Published: December 2023

Background:
Right ventricular dysfunction is recently referred as an independent predictor of sudden cardiac death. The purpose of this study was to evaluate the efficiency of risk stratification methods for appropriate implantable cardiac defibrillator (ICD) therapy using two different modalities to quantify the right ventricular function.

Methods:
Consecutive patients undergoing ICD implantations who completed both preprocedural echocardiography and cardiac magnetic resonance (CMR) were retrospectively enrolled. Any channelopathy or arrhythmogenic right ventricular disease were excluded. The right ventricular fractional area change (RVFAC) and estimated pulmonary artery pressure (EPAP) were calculated from echocardiography. The contraction-pressure index (CPI) was defined as the quotient of the RVFAC divided by EPAP. The right ventricular ejection fraction (RVEF) was automatically provided by CMR. Both were evaluated to predict the initial appropriate ICD therapy.

Results:
In total, 111 patients (59.5±14.9 years, 79 males) including 20 with ischemic cardiomyopathy were retrospectively enrolled. Fifty-six patients received an ICD as secondary prophylaxis. The mean RVFAC, CPI, and RVEF were 36.7±8.9%, 1.4±0.7%, and 39.9±13.8%, respectively. Regarding appropriate ICD therapy events, the best cut-off value of the RVFAC was 34.8 (specificity 0.63, sensitivity 0.65, ROC-AUC 0.64), CPI 1.59 (specificity 0.42, sensitivity 0.94, ROC-AUC 0.61) and RVEF 43.0 (specificity 0.48, sensitivity 0.87, ROC-AUC 0.64). The hazard ratio of a low RVFAC was 3.13 (95%CI: 1.32-7.44, P<0.01, concordance=0.62), that of low CPI was 9.60 (95%CI: 1.27-72.4, P=0.03, c=0.65), and that of reduced RVEF was 5.55 (95%CI: 1.64-18.7, P<0.01, c=0.67).

Conclusion:
CPI and RVEF were similarly associated with an increased appropriate ICD therapy. The CPI seemed to provide an equivalent stratification for the risk of appropriate ICD therapy as compared to a CMR indicator.
Abstract 15107: Dramatic Impact of a Liaison-Mediated Referral Strategy on Cardiac Rehabilitation Participation After Percutaneous Coronary Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Mansour Alexandra I , Seth Milan , Thompson Mike P , Casey Mary , Keteyian Steven J , Smith Frank , Gurm Hitinder S , Sukul Devraj
Published: December 2023

Background:
While cardiac rehabilitation (CR) improves outcomes after percutaneous coronary intervention (PCI) it remains underutilized. A liaison-mediated referral, where a healthcare professional explains CR’s benefits and places a referral before discharge, may promote CR use.

Hypothesis:
We hypothesize a liaison-mediated CR referral is associated with greater CR participation after PCI.

Methods:
This was a retrospective cohort study of patients who underwent PCI across 48 hospitals in Michigan between January 2021 and April 2022 and were referred to CR before discharge. Clinical registry data was linked to Medicare and commercial claims to identify the primary outcome of CR participation, defined as attending ≥1 CR session within 90 days of discharge from the index PCI admission. Bayesian hierarchical logistic regression modeling was used to compare CR participation between patients with and without a liaison referral, adjusting for patient characteristics. Cox-proportional hazard modeling was used to compare days elapsed between discharge and first CR session between liaison cohorts.

Results:
Among 9,023 patients referred to CR after PCI, 4,323 (47.9%) underwent a liaison referral and 3,390 (37.6%) attended ≥1 CR session within 90 days of discharge. The liaison and non-liaison cohorts had a mean age of 69.3 vs 69.4 years, and 68.3% vs 68.4% were male, respectively. The liaison cohort had a higher unadjusted 90-day CR participation rate compared with the non-liaison cohort (Figure). After adjustment, the liaison cohort had a significantly higher odds of attending ≥1 CR session and a shorter delay in attending the first session compared with the non-liaison cohort (28 vs 33 days, p<0.001) (Figure).

Conclusion:
A liaison-mediated CR referral is associated with higher odds of post-PCI CR participation and may mitigate delays in CR enrollment. This may be an effective referral strategy to improve CR participation rates and patient outcomes after PCI.
Abstract 15117: Estimating Ejection Fraction From the 12 Lead Electrocardiogram in Acute Heart Failure
Authors: pokhrel bhattarai sunita , Carey Mary G , Dzikowicz Dillon J , Mummidi Sudhir Kumar K , Aktas Mehmed
Published: December 2023

Introduction:
The 2022 AHA Guidelines for the Management of Heart Failure (HF) emphasized initiating guideline-directed medical therapy (GDMT) as early as possible during acute hospitalization. GDMT significantly differs between HF patients with reduced and preserved ejection fraction (EF). The electrocardiogram (ECG) is one of the first tests performed to assess cardiac function among HF patients.
Purpose:
To develop a linear model to estimate EF using the ECG and clinical covariates.

Methods:
Medical record data from 2020-21 of HF patients
>
18 years and positive Framingham Heart Failure Diagnostic Criteria excluding those with ventricular assist devices were extracted. Demographics, NYHA class, EF, and comorbidities, 12-lead ECG closest to the time of the echocardiogram were analyzed. We extracted 312 different features from the ECG using the Philips DXL Algorithm. Recursive LASSO regression was used to identify a subset of features in domain blocks. All analyses were completed in RStudio (4.3.0).

Results:
Among 126 patients (age 69.4
+
15.5 years; BMI 31.2
+
8.2 kg/m
2
; EF 40
+
19%; the time between ECG-echocardiogram 13.30
+
40.67 hours: minutes), the predominant cardiac rhythm (70%, n=88) was sinus. Among the 312 ECG features, 39 (13%) were significant; the final linear model included 9 (3%) features: S Duration V1, QRS Duration III, Horizontal T Angle, Mean Heart Rate, Q Duration aVL, Maximum QRS Angle, R Duration V3, S Amplitude V3, and P amplitude V3. The final linear model achieved an R
2
=0.498 and adjusted R
2
=0.459. We adjusted the model for age, body mass index, and sex, and model performance improved by R
2
=0.107 adjusted R
2
=0.104. The addition of time between ECG-echocardiogram to the model did not significantly change performance. From the predicted values, 50% (n=63) were within the margin of error, and the correlation between predicted and true values was moderate (r=0.629 [95%CI, 0.510-0.724]). The mean difference between predicted and true EF values varied between
+
12.06%.

Conclusions:
Our initial results demonstrate the ability to estimate EF using a 12-lead ECG. While the results are limited due to the small sample size and significant time between ECG and echocardiogram, these preliminary results support the feasibility of future research.
Abstract 15120: Effect of Prolonged Left Ventricular Global Longitudinal Strain Reduction After Exercise on the Development of Cardiovascular Events
Authors: Ishii Katsuhisa , Usami Shunsuke , Kinoshita Minako , Miyagawa Kotaro , Hayano Mamoru , Hatani Takeshi , Aono Yuya , Seo Hidenobu , Asada Satoshi , Kaji Shuichiro
Published: December 2023

Introduction:
Recently, it has also been reported that patients with ischemic heart disease have prolonged left ventricular (LV) GLS reduction after exercise.

Hypothesis:
To investigate the influence of prolonged LV GLS reduction after exercise on the development of cardiovascular events.

Methods:
One hundred thirty-three consecutive patients with at least one of the following coronary risk factors: hypertension, hyperlipidemia, or diabetes mellitus underwent echocardiography (ARTIDA; Canon medical, Japan) before and 30 minutes after Master double exercise and LV GLS was measured offline (Vitria; Canon medical, Japan). Patients with obvious LV wall motion abnormalities, significant valvular heart disease, or atrial fibrillation were excluded. The incidence of cardiovascular events was determined from the patients' medical records. Patients were divided into three groups based on the occurrence of cardiovascular events up to 6 months after the examination: non-events group, minor cardiovascular event group (chest pain, palpitations, other additional tests), and major cardiovascular event group (coronary revascularization, cardiac hospitalization). The LV GLSs before and 30 minutes after exercise were compared in each patient group.

Results:
Mean age was 63±11.5years (female: 25%). Patients had hypertension (53%), hyperlipidemia (47%), and diabetes (65%). Of the 133 eligible patients, non-event group (n=68), minor cardiovascular event group (n=50), and major cardiovascular event group (n=15). LV GLS before exercise was not significantly different between the groups, however LV GLS at 30 minutes after exercise were significantly lower in the cardiovascular event groups and were proportional to the severity of the event. (Figure)

Conclusions:
The prolonged reduction in LV GLS after exercise could be a useful predictive index for the development of cardiovascular events.
Abstract 15121: Bioresorbable Molybdenum Electrodes: Towards a Novel Generation of Temporary Epicardial Pacing Wires
Authors: Prieto Jarabo Maria Elisa , Redlich Christian , Schauer Antje , Guder Celine , Poehle Georg , Weissgaerber Thomas , Adams Volker , Kappert Utz , El-Armouche Ali , Linke Axel , Wagner Michael
Published: December 2023

Introduction:
Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Removal is recommended on day 4-7. Occasionally, TEPW cannot be mechanically extracted, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW that will dissolve over time even if postoperative removal is unsuccessful.

Methods and Results:
We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 μM diameter each, length 18 cm for ex-vivo, 7.5 cm for in-vivo trials) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 μg/cm
2
·d (n=5) compared to uncoated electrodes with 30.3 ± 0.8 μg/cm
2
·d (n = 4, p < 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test Mo TEPW in vivo, we sutured them epicardially onto the anterior wall of hearts of female Wistar rats, led them out of the thorax and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation, after two weeks and one month. Mo electrodes showed similar pacing and sensing properties directly upon implantation and after two weeks. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Conventional steel TEPW had similar electrical properties following implantation, after two weeks and one month with no signs of breakage.

Conclusion:
We demonstrate that Mo TEPW can feasibly be used for epicardial pacing in vivo for up to two weeks. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.
Abstract 15133: Topic Models Using Notes From Electronic Medical Records Can Classify Non ST Elevation Myocardial Infarction Patients Based on the Presence of an Occluded Culprit Artery
Authors: Dzikowicz Dillon J , Aktas Mehmed , Wang Linwei , Zareba Wojciech
Published: December 2023

Introduction:
Approximately 33% of patients with a Non-ST-Elevation Myocardial Infarction (NSTEMI) have an occluded culprit artery which doubles their odds of adverse outcomes. Earlier identification of NSTEMI patients with occluded culprit artery may reduce their odds of adverse outcomes. Notes from the electronic health record (EHR) are rich sources of text data about signs and symptoms. Organizing text data into topics may help providers identify patients with NSTEMI and an occluded culprit artery sooner. Latent Dirichlet Allocation uses a deep-learning network to generate topics that can classify patients.

Methods:
Notes transcribed during the first 72 hours of hospitalization were extracted from the EHR among NSTEMI patients who presented to a medical center between 2015-2020. The data was preprocessed by removing punctuation, numbers, and stop words. We decided 5 topics based on computed coherence value. Two authors determined whether the first 100 terms were associated with an occluded artery. Analyses were completed in R using packages
topicmodels
and
tidyverse
.

Results:
We examined 45,025 notes from 2,223 patients (age=69
+
14 years old; 57% n=1267 male; 83% n=1,845 White) who experienced 2,685 hospitalizations (17%, n=462 NSTEMI re-hospitalizations). In Topic 1, 70% of the terms were associated with an occluded culprit artery including “chest pain” and “troponin”. In contrast, in Topic 5, 90% of terms were
not
associated with an occluded culprit artery such as “edema” and “pulmonary”. Figure 1 shows the frequency of terms associated with an occluded artery per topic.

Conclusions:
Topic 1 is most associated with an occluded culprit artery. Topic 5 is the least associated with an occluded culprit artery, instead associated with heart failure. Our results demonstrate it is feasible to develop topics to differentiate NSTEMI with and without an occluded culprit artery. Future research aims to identify patterns between signs and symptoms within topics.
Abstract 15165: Clinical Characteristics and Outcome of Venous Thromboembolism in Patients After Surgical Procedure: From the COMMAND VTE Registry-2
Authors: Usami Shunsuke , Kaji Shuichiro , Miyagawa Kotaro , Kinoshita Minako , Asada Satoshi , Kaneda Kazuhisa , Yamashita Yugo , Kimura Takeshi
Published: December 2023

Background:
Undergoing surgical procedure is a risk factor for venous thromboembolism (VTE). However, the prognosis of VTE in patients after surgical procedure has not been fully evaluated in the Era of direct oral anticoagulant (DOAC). We elucidated the prognosis of VTE in patients who have undergone surgical procedure.

Methods:
The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. According to the history of surgical procedure within 2 months, we divided the study patients into 2 groups; Surgical group (N=793) and Non-surgical group (N=4404). Clinical outcome including all-cause death and recurrence of VTE was compared between the two groups.

Results:
There were more women in surgical group than non-surgical group (64% vs. 58%, P<0.01). In addition, surgical group had higher prevalence of active cancer (34% vs. 28%, P<0.01), and lower prevalence of kidney disease (16% vs. 20%, P<0.01) than non-surgical group. The cumulative incidences of all-cause death and recurrent VTE at 2-year were significantly lower in surgical group than non-surgical group (all-cause death: 16.6±1.4% vs. 24.4±0.7%, P<0.01; recurrent VTE: 2.8±0.7% vs. 5.7±0.4%, P<0.01, respectively). In surgical group, Cox regression analysis identified diabetes mellitus as the independent risk factor for recurrence of VTE (hazard ratio 2.90; 95% confidence interval, 1.24-6.74; P=0.01).

Conclusion:
Patients after surgical procedure had lower mortality and incidence of recurrent VTE than non-surgical group. Diabetes mellitus is the independent risk factor for recurrence of VTE in patients after surgical procedure.
Abstract 15168: The Role of Mitochondrial Fission Factor (MFF) and Increased Midzone Mitochondrial Fission in Pulmonary Arterial Hypertension: Implications for Proliferation, Mitophagy, and Apoptosis
Authors: Colpman Pierce , Chen Kuang-Huieh , Mewburn Jeffrey , Goodall-Halliwell Ian , Das Gupta Asish , Archer Stephen L
Published: December 2023

Introduction:
The obstructive vasculopathy in pulmonary arterial hypertension (PAH) results from unrestricted proliferation and impaired apoptosis of pulmonary artery smooth muscle cells (PASMC). This pseudoneoplastic phenotype is partly due to increased mitotic fission i.e. the highly coordinated processes of mitochondrial fission and nuclear division. Two types of mitochondrial fission have been reported: peripheral fission, which eliminates damaged terminal portions of mitochondria via mitophagy, and midzone fission, which is linked to mitochondrial biogenesis and cellular proliferation. While all fission involves dynamin related protein 1 (Drp1), the Drp1 binding partner differs between these processes with mitochondrial fission factor (MFF) mediating midzone fission, whilst fission protein 1 (Fis1) governs peripheral fission. Here we explore the role of MFF and Fis1 in the pathogenesis of PAH.

Hypothesis:
Midzone fission is increased in PAH PASMC and inhibiting midzone fission by downregulating MFF will decrease cell proliferation and induce apoptosis.

Methods:
MitoMeter, a mitochondrial segmentation and tracking application, was adapted for automated analysis of the location of mitochondrial fission events. Immunoblots were used to assess the expression of MFF and Fis1 in control (n=4) vs. PAH (n=5) human PASMC. Flow cytometry was used to assess cell proliferation (EdU) and rates of apoptosis (Annexin V) (n=3).

Results:
Midzone fission, as a % of total fission events, is increased (PAH= 48.7%±6.9, Ctrl = 28.9%± 5.1p<0.05). Moreover, MFF expression is increased in PAH PASMC (p<0.05). Conversely, peripheral fission is decreased (PAH=51.2%±6.9, Ctrl = 71.0±5.1). Silencing MFF inhibited midzone fission (siCtrl=54.93.1%, siMFF = 39.37.4%), while Fis1 knockdown inhibited peripheral fission in PAH PASMC (siCtrl = 45.13.1%, siFis1 = 36.91.9%), p<0.05 each. Inhibiting MFF inhibited PAH PASMC proliferation (siCtrl =36.50.9%, siMFF = 23.50.5%, p<0.05) and induced apoptosis in PAH PASMC (siCtrl=3.90.3% versus siMFF 7.40.2%, p<0.05).

Conclusion:
MFF mediated midzone fission is upregulated in PAH PASMC contributing to increased proliferation, and reduced apoptosis. Inhibiting MFF may be a new therapeutic strategy in PAH.
Abstract 15177: Unloading Reveals a Latent Cardiomyocyte Regeneration Potential in the Human Heart
Authors: Derks Wouter , Rode Julian , Collin Sofia , Rost Fabian , Heinke Paula , Hariharan Anjana , Pickel Lauren , Simonova Irina , Lázár Eniko , Graham Evan , Jashari Ramadan , Andrä Michaela , Jeppsson Anders , Salehpour Mehran , Alkass Kanar , Druid Henrik , Kyriakopoulos Christos , Taleb Iosif , Shankar Thirupura S S , Selzman Craig , Sadek Hesham A , Jovinge Stefan , Brusch Lutz , Frisen Jonas , Drakos Stavros G , Bergmann Olaf
Published: December 2023

Introduction:
Cardiomyocytes in the adult human heart show a minimal regenerative capacity. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure (HF) has been controversial. Advanced HF patients can be supported with a left ventricular assist device (LVAD) and a subset of these patients show significant functional and structural cardiac improvement (termed responders). It remains unknown how mechanical unloading affects cardiomyocyte renewal, and if there is a difference between responders and non-responders.

Hypothesis:
Mechanical unloading differentially induces cardiomyocyte renewal in responders and nonresponders.

Methods:
We determined cardiomyocyte renewal by measuring the 14C concentration of cardiomyocyte genomic DNA. We included 52 patients with advanced HF, 28 of whom received LVAD support. Nuclear ploidy and the number of nuclei per cardiomyocyte were measured using both flow cytometry and image cytometry to distinguish the extent of non-productive cell cycle activity from proliferation. To integrate the measured 14C concentrations with the data on cardiomyocyte DNA synthesis mathematical modeling was performed and used to investigate renewal in HF, with and without mechanical unloading.

Results:
Cell cycle activity increased in failing hearts rather than renewal, which was reduced >18-fold in non-ischemic and >50-fold in ischemic failing hearts compared to healthy hearts. Conversely, LVAD responders showed a >6-fold increase in cardiomyocyte renewal relative to a healthy heart.

Conclusions:
LVAD-mediated functional cardiac improvement was accompanied by cardiomyocyte renewal, indicating a latent potential for regeneration in the adult heart.
Abstract 15188: Mid-Cavity Takotsubo Cardiomyopathy Post CAR T-cell Therapy
Authors: Oberoi Mansi , Garvin Robbie , Christensen Cason , Porter Thomas R
Published: December 2023

Introduction:
CAR T-cell therapy has been reported to have cardiovascular (CV) adverse effects mostly in context of cytokine reconstitution syndrome (CRS). Although pathophysiology of CAR T-cell cardiotoxicity (CTCC) is not fully understood, it is thought to be IL-6 mediated which has been implicated as a mediator of myocardial depression in infectious and inflammatory states. Another mechanism is direct cardiotoxicity from potential cross-reactivity with unrelated peptides expressed by normal tissue. We present a case of Takotsubo cardiomyopathy following CAR T cells.

Case:
61 year old male with h/o Waldenstrom's macroglobulinemia, DMT2, HLD was admitted for CAR T cell therapy. Following infusion, he developed chills, diaphoresis, tachypnea, tachycardia, chest tightness lasting several hours. EKG had dynamic ST depressions in inferolateral leads with elevated hstroponin (6000 pg/ml). Despite severe pancytopenia, heparin was started for acute coronary syndrome. Pain resolved with morphine and he received tocilizumab for CRS. Echo showed a mid-cavitary variant of Takotsubo involving right and left ventricles with depressed systolic function (LVEF 30-35%; Image). Coronary angiogram was deferred due to bleeding risk. Repeat echo in 2 days showed persistent mid-cavity hypokinesis with slight improvement in LVEF (40%) after initiating beta blocker. The temporal relation of acute mid-cavity dysfunction to CAR T-cells indicates most likely CTCC. Heparin was stopped and he was managed conservatively with plan to reassess LVEF in 2 months.

Conclusion:
Patients undergoing CAR T-cell therapy should be assessed for CV symptoms using biomarkers and imaging for early detection of cardiotoxicity and prompt initiation of supportive treatment. We present a case of acute mid-cavity left ventricular dysfunction (a Tako-tsubo variant) that was temporally related to CAR T cell infusion. Further studies are needed to determine the frequency of this acute form of CTCC.
Abstract 15192: The Impact of Fontan Circulatory Failure on Heart Transplant Survival: A 20 Center Study
Authors: Schumacher Kurt R , Rosenthal David N , Batazzi Adriana , Yu Sunkyung , Reichle Garrett , Bano Maria , Deshpande Shriprasad R , O'Connor Matthew , Ahmed Humera , Chen Sharon , Wright Lydia , Kindel Steven J , Joong Anna , Ploutz Michelle , Feingold Brian D , Godown Justin , Mao Chad Y , Lorts Angela , Simpson Kathleen , Ybarra Aecha , Richmond Marc E , Amdani Shahnawaz , Conway Jennifer , Blume Elizabeth , Cousino Melissa
Published: December 2023

Introduction:
Fontan circulatory failure (FCF) is a chronic state in palliated single ventricle heart disease with high morbidity and mortality including heart failure, multisystem end-organ disease, and need for heart transplant (HT). Specific FCF morbidities have not been rigorously defined limiting study of how FCF morbidities impact pre- and post-HT outcomes.

Hypothesis:
FCF-specific morbidities affect survival from HT waitlisting (WL) through 1-year post-HT.

Methods:
This 20-center, retrospective cohort study collected demographic, medical/surgical history, WL data, and peri- and post-HT data in Fontan patients WL since 2008. Using Delphi methodology, investigators defined FCF-specific morbidities and collected data. Appropriate univariate 2-group statistics compared surviving individuals with those who 1) died anytime from WL to 1-year post-HT, 2) died on the WL, 3) died within 1-year post-HT. Multivariable logistic regression determined independent risk factors for mortality between WL and 1-year post-HT.

Results:
Of 409 WL patients, 24 (5.9%) died on the WL. Of the 316 (77%) who underwent HT, 27 (8.5%) did not survive to 1-year. Univariate risk factors for WL death included higher aortopulmonary collateral burden, > 1 hospitalizations in prior year, younger age, sleep apnea, higher NYHA class, non-enrollment in school or work, and single-parent home. Risk factors for 1-year post-HT mortality included HLHS diagnosis, patent fenestration, anatomic Fontan obstruction, clinical cyanosis (pulse oximetry < 90%), polycythemia, portal variceal disease, psychiatric disease requiring treatment, and higher HLA class II PRA. For the 15% of patients not surviving from WL to 1-year post-HT, independent risk factors for mortality included >1 hospitalization in the year prior to WL (aOR 2.0, p=0.05) and clinical cyanosis (aOR 5.0, p=0.002). Notably, some FCF morbidities did not impact post-WL survival including protein-losing enteropathy, plastic bronchitis, and kidney disease.

Conclusions:
Fontan-palliated patients continue to have high mortality from WL through HT. Among FCF specific morbidities, cyanosis is associated with worsened survival and needs further study. Continued study of FCF phenotype is possible via this dataset.
Abstract 15255: Auscultation and ECG for Detection of Valvular Pathologies and Ventricular Dysfunction: Can Machine Learning Help?
Authors: Makimoto Hisaki , Shiraga Takeru , Imai Yoshie , Itani Yusuke , Schölzel Fabian , Rana Obaida , Kelm Malte
Published: December 2023

Introduction:
Simple testing methods such as auscultation and electrocardiogram (ECG) that are widely used may offer easy opportunity for early diagnosis of cardiac pathologies and lead to prompt treatment.

Hypothesis:
Combination of multiple simple testing using machine learning (ML) will achieve diagnostic efficiency on valvular pathologies and ventricular dysfunction.

Methods:
Auscultation at three locations (second right sternal border, Erb, apex) and 12-lead electrocardiograms (ECG) were collected in 1052 patients undergoing echocardiography. Independent cases (N=103) were also enrolled for clinical validation. The cardiovascular diseases targeted for detection were severe aortic stenosis (AS), severe mitral regurgitation (MR), and left ventricular dysfunction (LVD) with ejection fraction ≤40%. Best neural networks were obtained by four-fold cross-validation training using heart sounds and ECG (12-lead, limb-lead and precordial-lead). The output from each model was integrated into one diagnostic prediction by stacking technique. The model performance was verified in the clinical validation cohort by area under the receiver-operator-characteristics curve (AUC).

Results:
The best performance was achieved by stacking auscultation of all three locations and 12-lead ECG for all three pathologies (AUC = 0.931 for AS, 0.801 for MR, and 0.736 for LVD). The contribution analyses demonstrated diverse patterns of diagnostic contributions of the auscultatory locations and ECG types depending on the target diseases. For AS detection, the heart sound played a greater role compared to the limb- and precordial ECG. Auscultatory and electrocardiographic data contributed similarly for MR detection. For LVD detection, the 12-lead ECG contributed largely followed by the heart sound at Erb.

Conclusions:
Severe AS, severe MR, and left ventricular dysfunction, which are currently only definitively diagnosed by imaging, can be detected with high efficiency by ML models combining auscultation and electrocardiography with synergistic effect. The contribution of each testing data differs depending on the target diseases. Our data suggests that single-modal AI may not necessarily diagnose multiple diseases.
Abstract 15270: Macrophage ADAR1 Regulates Atherosclerosis Development Through Editing-Independent Degradation of PPAR-γ
Authors: Cai Dunpeng , Murashita Takashi , Markley John , Chen Shiyou , Fujise Ken , Bowles Douglas K
Published: December 2023

Background:
Macrophage activation and vascular inflammation play important roles in atherosclerosis. Non-editing functions of adenosine deaminase acting on RNA (ADAR1) in macrophage activation and atherosclerosis remain elusive.

Methods:
Nonvascular ADAR1 in atherosclerosis progression was investigated via aortic transplantation and bone marrow transplantation. ApoE-/- mice combined with macrophage-specific ADAR1 deficiency were used to determine macrophage-specific roles of ADAR1 in atherosclerosis. Human coronary atherosclerotic specimens were utilized to establish the relevance to human atherosclerosis. Moreover, a humanized atherosclerosis model was created to examine the influence of human macrophages in human arteries.

Results:
ADAR1+/– attenuates atherosclerosis. Allograft transplantation of wild-type abdominal aorta into ADAR1+/– recipient mice promoted atherosclerosis. Likewise, bone marrow transplantation from wild-type mice to ADAR1+/– recipient mice negated the protective effects of ADAR1+/–, suggesting that nonvascular ADAR1 is instrumental for atherosclerosis progression. ADAR1 deficiency in hematopoietic cells lessened the prevalence and severity of atherosclerosis, and impeded macrophage infiltration, foam cell formation, and aortic wall inflammation. Mechanistically, ADAR1 deletion deterred classical macrophage activation and foam cell formation via downregulation of PPAR-γ, which was mediated by enhancing ubiquitination and further degradation of PPAR-γ. Importantly, ADAR1 was upregulated in macrophages in human atherosclerotic lesions. Transplantation of ADAR1-deficient human monocytes, rather than their wild-type counterparts, into hyperlipidemic immunodeficient mice suppressed the formation of atherosclerosis in transplanted arteries from patients undergoing coronary artery bypass grafting surgery due to coronary artery blockade by atherosclerotic plagues. Interestingly, ADAR1 suppression in macrophages noticeably augmented the anti-atherosclerotic effect of the PPAR-γ agonist rosiglitazone.

Conclusions:
These results demonstrate that noncanonical ADAR1 plays an essential role in the regulation of macrophage activation and atherosclerosis development.