bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14497: Predictors of Hypertensive Response During Stress Echocardiography
Authors: Bontu Sneha , Kunchakarra Siri , Brailovsky Yevgeniy , Martin Brendan , Maharaj Valmiki , Sanagala Thriveni
Published: June 2023

Introduction:
Hypertensive response during stress echocardiography has been predominately studied in a healthy population without many comorbidities, unlike the patients for which these tests are indicated. We performed a retrospective study identifying clinical predictors of hypertensive response to both exercise (EXE) and dobutamine (DSE) stress echo.

Methods:
Retrospective analysis was performed on all patients who underwent stress echo from January 1, 2015 to February 28, 2017 in a tertiary care academic center. Patient demographics, comorbidities, medications and stress echo parameters were evaluated. Patients were characterized based on stress echo completed as EXE or DSE. The primary outcome was hypertensive response.

Results:
4670 patients were enrolled: 1238 in the DSE group and 3432 in the EXE group. On multivariable analysis, only resting SBP remained a significant predictor of hypertensive response during DSE (odds ratio (OR) per 20mmHg 3.21, CI 1.57-6.59,
p
=.001) with an AUC of 0.76. On multivariable analysis, obesity (OR 2.27, CI 1.08-4.8,
p
=.03), diabetes (OR 3.24, CI 1.22-8.6,
p
=.02), resting SBP (OR 4.44, CI 2.35-8.38,
p
<.001), and black race (v. white, OR 4.53, CI 1.62-12.67,
p
=.004) remained significant predictors of hypertensive response during EXE, with an AUC of 0.82.

Conclusions:
Elevated resting systolic blood pressure is a strong predictor of hypertensive response in both groups. Controlling resting blood pressure prior to stress testing reduces non-diagnostic test results and improves safety.
Abstract 14511: A Single Center Experience With the Safety and Feasibility of Concomitant Atrial Fibrillation Ablation and Left Atrial Appendage Occlusion: Six-Month Outcomes
Authors: Alzahrani Ashraf , Karmali Rehan , Berglund Felix , Sajja Himanshu , Klein Benjamin , Syed Alveena , Donnellan Eoin , Wazni Oussama M , Taigen Tyler , Kanj Mohamed H
Published: June 2023

Introduction:
Given the procedural similarities between atrial fibrillation (AF) catheter ablation and left atrial appendage (LAA) occlusion, interest has grown over recent years in combining them into a single concomitant procedure as a strategy for rhythm control and stroke prevention. We report on the short-term outcomes of the combined procedure in a single center case series.

Methods and Results
Data was gathered by retrospective chart review. Between June 2015 to August 2021, 242 patients (61% male, mean age 72 ± 8, CHA2DS2-VASc 3.8 ± 1.3, HAS-BLED 2.5 ± 1.1) underwent concomitant AF ablation and LAA occlusion with the Watchman device. Successful occlusion occurred in 224 patients (93%) with a mean procedural time of 182 ± 76 minutes, mean maximum compression of 25 ± 5.5%, and a median number of 1 device. Reasons for aborting included anatomic difficulties (83%), the presence of sludge or thrombus in the LAA (11%), and edema at the site of ablation in only 1 case (6%). Peri-procedural complications included 2 cases of left atrial appendage perforation requiring surgical device extraction, 1 stroke, 6 cases of pericarditis, and 4 vascular access site complications including 1 retroperitoneal bleed, 1 superficial hematoma, 1 persistent bleeding requiring admission, and 1 arteriovenous fistula. 205 patients (92%) had appropriate follow-up within 6 months. Anticoagulation was successfully discontinued in 90 patients (44%) at 3 months, and 178 patients (87%) at 6 months. Antiarrhythmics were discontinued in 25 patients at 3 months (12%) and 35 patients at 6 months (17%). Ninety-day complications included 12 cases of gastrointestinal bleeding, 4 cases of genitourinary bleeding, 3 cases of volume overload, 2 cases of epistaxis, and 1 intracerebral hemorrhage. All patients with repeat imaging (95%) over a mean follow-up duration of 93 days remained with adequate occlusion, with 5 cases of device thrombosis (2%).

Conclusion
In conclusion, the combined procedures of catheter ablation for AF and LAA occlusion with the Watchman device appears to be safe and feasible. Further data are needed on long-term outcomes of arrhythmia recurrence, bleeding, and thromboembolic events to determine which patients might benefit most from the hybrid approach.
Abstract 14519: End Stage Heart Failure Patients With Do-Not-Resuscitate Code Status Have Dramatically Reduced Hospitalization Cost and Length of Stay
Authors: Masri Abdelrahman , Abbasi Ayesha , Shoura Sami , Almani Muhammad Usman , Murthi Mukunthan , Masri Abdallah
Published: June 2023

Introduction:
End-stage CHF (ES-CHF) poses a significant burden on healthcare system, DNR orders are often associated with comfort care measures, decreased pain and suffering, as well as healthcare resource utilization (cost and LOS).

Objective:
To quantify the discrepancy in cost and LOS between ES-CHF patients with DNR orders versus without DNR code status.

Methodology:
Nationwide Inpatient Sample (NIS) database years 2017-2018 was invoked for hospitalizations with primary or secondary diagnosis of ES-CHF, DNR status, comorbidities, and hospitalization outcome using ICD-10 codes. Characteristics of ES-CHF hospitalization with DNR versus no DNR code status were compared. Because of the nature of NIS database, timing of diagnoses and DNR code status could not be established, thus regression analysis for predictors of hospital charges, cost, and LOS was not feasible. Regression analyses were performed to explore predictors of mortality. Stata/MP 16.0 software was used.

Results:
40,655 adult hospitalization had the diagnosis of ES-CHF in years 2017-2018 in the United States, among them, 12,300 (30%) had DNR code status, 35% were females, 83% of patients had >=3 comorbid conditions (Charlson comorbidity index>=3). Overall inpatient mortality rate was 12% (25% vs 7% in DNR vs no DNR group, respectively, p<0.001), mean LOS was 10+-15 days (8 vs 11 days in DNR vs no DNR group, respectively, p<0.001), mean total hospital charges was $159,122+-358,186 ($79,434 vs $193,873 in DNR vs no DNR group, respectively, p<0.001). Significantly higher rates of CABG history, atrial fibrillation, COPD, peripheral vascular disease, hypothyroidism, CKD, liver disease, electrolyte disturbances, AKI, and sepsis were found among DNR group. In all patients with ES-CHF, independent predictors of inpatient mortality included older age, DNR status, history of CABG, peripheral vascular disease, liver disease, electrolyte disturbances, smoking, AKI, and sepsis.

Conclusion:
The presence of DNR code status in ES-CHF patients admitted to the hospital for any was associated with had dramatically reduced hospital charges and cost by more than the half, and with significantly shorter LOS.
Abstract 14549: Malignant Anomalous LMCA With an Interarterial Course:
Atypical Presentation
Authors: Baker Preston , Elkaronyi Ahmed , Darki Amir
Published: June 2023

A 42-year-old healthy female presented to the emergency department with coughing and shortness of breath, complicated by syncope. Before loss of consciousness, the patient reported feeling lightheaded, but no chest pain or palpitations were appreciated. Following a negative work up for cardiogenic syncope, she was discharged home with a presumed diagnosis of vasovagal syncope. Over the next 12 months, the patient had recurrent episodes of shortness of breath followed by either a presyncopal prodrome or full syncopal episodes. Each episode came on with coughing and dyspnea without significant exertion. 18 months after the original event, she was re-evaluated for cardiac etiologies of her symptoms, and CT coronary angiogram showed an anomalous left main coronary artery arising from the right coronary cusp (AAOLCA) with an interarterial course, which was subsequently confirmed on coronary angiography (figure 1).

Anomalous Left Coronary Arteries of Aortic Origin (AAOLCA) present a diagnostic dilemma for cardiologist, given their vague presenting symptoms, unknown prevalence in the general population, and high risk for Sudden Cardiac Death (SCD). This patient’s syncopal episodes and presyncopal symptoms that were inconsistent with a cardiac etiology represent an atypical presentation, although there is no classic presentation for which AAOLCA is the most likely diagnosis. AAOLCA’s with an interarterial course, as seen in this patient, account for the majority of SCD caused by anomalous coronary arteries, despite making up just 1.3% of all identified cases. Referral for surgical correction is recommended for all patients AAOLCA with an interarterial course, to reduce risk of SCD. Further research is warranted regarding the true prevalence of AAOLCA in the general population, the risk of SCD associated with various AAOLCA’s, and validated screening tools for utilization of coronary CTA or MRA to identify AAOLCA’s prior to major cardiac events.
Abstract 14556: Deep Phenotyping APOC3 Knockouts in a Population With High Consanguinity
Authors: Khalid Shareef , Khan Maleeha Z , Wu Liya , Jahanzaib Muhammad , Saeed Subhan , Mian M. Rehan , Liaqat Muhammad Bilal , Rasheed Asif , Millar John S , Rader Daniel J , Saleheen Danish
Published: June 2023

Apolipoprotein C-III (APOC3) plays an integral role in the regulation of triglyceride-rich lipoproteins, by inhibiting the clearance of triglycerides carried by VLDL and chylomicron remnants in the blood. Prior work has shown that heterozygous loss of function (LOF) carriers of APOC3 have lower triglyceride levels and a lower risk of coronary artery disease (CAD). The quantitative impact of disease risk remains unknown in complete knockouts (KOs). Additionally, the effects and safety implications of complete APOC3 LOF have not been characterized. APOC3 inhibition is an active therapeutic strategy to lower CAD risk; hence these questions have therapeutic relevance. Among 37,244 unrelated sequenced individuals, including 19,681 cases of myocardial infarction (MI), in the Pakistan Genomic Resource - a biobank with high levels of consanguinity - we identified 207 heterozygous LOF carriers and 14 KOs. As expected, the KOs had undetectable APOC3 levels. We also observed a decrease in plasma triglycerides (P = 9E-85), VLDL-C levels (P = 2E-73), APOE levels (P = 5.4E-9) and an increase in HDL-C levels (P = 1E-34) and APOA1 levels (P = 6E-5) consistent with a gene-dosage effect. We observed a significant decrease in the risk of MI among heterozygous carriers (P = 0.01); however, we did not observe any protection from MI risk in complete KOs. Conversely, we observed a non-significant increase in the risk of MI in complete KOs compared to non-carriers; of the 14 knockouts identified, 9 were found to have MI. The loss of protection against MI could not be explained by the genetic background or by the increase in levels of homozygosity of the KOs. By recalling complete KOs and their family members, we were able to identify and phenotype an additional 33 complete KOs and 152 heterozygotes and assess other safety concerns related to complete APOC3 inhibition (i.e., glucose intolerance, fat content in the liver, etc.). In conclusion, by leveraging a highly consanguineous cohort, we have identified and phenotyped APOC3 KOs that have, hitherto, not been identified elsewhere. We did not observe APOC3 LOF to confer protection in complete KOs and observed other biomarker and phenotypic associations; these findings should inform existing therapeutic programs targeting APOC3.
Abstract 14559: Anti-Arrhythmic Effects of Exosomes Isolated From Cardiosphere-Derived Cells in Rats With Heart Failure and Preserved Ejection Fraction
Authors: Cho Jae Hyung , Rajewski Alex , Bresee Catherine , Kim Myung Yoon , Mesquita Thassio , Jones Xaviar , Pellot Isabelle , Liu Weixin , Sanchez Lizbeth , Nawaz Asma , Ibrahim Ahmed G , Rogers Russell , Cingolani Eugenio , Marban Eduardo
Published: June 2023

Introduction:
Cardiosphere-derived cells (CDCs) reverse electrical remodeling and reduce inducible ventricular arrhythmias in rats with heart failure and preserved ejection fraction (HFpEF). Exosomes isolated from CDCs (CDCexo) have anti-arrhythmic effects in various animal models but have not been tested in models of HFpEF.

Hypothesis:
CDCexo, when given intravenously, reverse electrical remodeling and reduce spontaneous ventricular arrhythmias in rats with HFpEF.

Methods:
Dahl salt-sensitive rats were fed high-salt diet (containing 8% NaCl) to induce HFpEF from 7 weeks of age. Ambulatory electrocardiogram (ECG) devices were implanted in the peritoneum at 13 weeks of age to monitor spontaneous ventricular arrhythmias. Exosomes were harvested from media conditioned by human CDCs after 48 hours of exposure to hypoxia. Echocardiogram-verified HFpEF rats (at 14 weeks of age) were injected via tail vein with human CDCexo (n=8) vs. vehicle (IMDM media, n=8) weekly for 4 weeks. ECG parameters and spontaneous development of ventricular arrhythmias were compared between the two groups.

Results:
QTc interval was reduced in CDCexo-injected HFpEF rats compared to vehicle-injected HFpEF rats (262±15 ms vs. 287±25 ms, p=0.0001). Two of the eight HFpEF rats injected with vehicle showed a maximal premature ventricular contraction (PVC) burden per minute of 50% while only one HFpEF rat injected with CDCexo manifested 25% maximal PVC burden per minute. Five of eight HFpEF rats injected with vehicle showed non-sustained ventricular tachycardia (VT) while only one HFpEF rat infused with CDCexo developed non-sustained VT. One rat in the vehicle group undergoing telemetry monitoring died suddenly and the cause of death was sustained VT degenerating into ventricular fibrillation (VF). The number of VT/VF episodes per rat (including non-sustained VT and sustained VT/VF) was reduced in the CDCexo group compared to the vehicle group (0.4 [0-3] vs. 13 [0-56] episodes per rat, p=0.0443).

Conclusions:
CDCexo recapitulated the beneficial effects of CDCs in HFpEF rats: reversing electrical remodeling and reducing ventricular arrhythmias. More importantly, an intravenous delivery route was effective for CDCexo to confer their salutary effects to rats with HFpEF.
Abstract 14578: Dapagliflozin Attenuates Aorta Smooth Muscle Aging and Atherosclerosis
via
Inhibiting the PPARα Pathway
Authors: Zhang Weiwei , Han Dong , Wang Yabin , Ma Yan , Tian Lei , Cao Feng
Published: June 2023

Objective:
SGLT2 inhibitors reduce cardiovascular risks in ASCVD (Atherosclerotic cardiovascular disease) patients independently of glycemic control while the possible mechanisms remain unclear. Smooth muscle senescence is one of the major risk factors exacerbating AS (atherosclerosis). We hypothesized that dapagliflozin inhibits smooth muscle senescence and results in the reducing AS plaque area.
Methods & Results:
After treatment with dapagliflozin (10umol/L 12h), the cellular senescence and oxidative stress were decreased as measured by expression of P53 (-23%), P21 (-16%) and ROS production (-19%), (all p<0.05) in VSMC induced by the palmitic acid (PA). The trend was also revealed in the AS mouse model. The X-Gal positive VSMC (-20%, p<0.05) as well as the area of SA-β-Gal positive zone (-11%, p<0.05) were significantly reduced after dapagliflozin (0.1mg/kg/day) treatment for 12w. Further analysis of the atherosclerotic lesions revealed a reduction of AS plaque protrusion into the vessel lumen (-21%) and reduced the size of lipid necrotic area (-32%), the thickness of fiber cap (-15%), (all p<0.05), which were indications of instable atherosclerotic plaques. The effects of dapagliflozin on mice aorta were assessed by unbiased transcriptomic analyses. GO and KEGG analysis indicated alterations of the fatty acid metabolic, fatty acid oxidation and PPARα pathway after dapagliflozin treatment. Abnormal activation of PPARα in AS aorta and PA-treated VSMC, were inhibited by dapagliflozin (-18%, -35%, both p<0.05). The protection effects of dapagliflozin on VSMC could be abolished by the PPARα agonist.

Conclusions:
Dapagliflozin exerts beneficial protecting effects on smooth muscle from senescence and ameliorating lipotoxicity in atherosclerosis by inhibiting the PPARα pathway. These findings suggest a novel mechanistic basis for SGLT2 inhibitor attenuating atherosclerosis mediated by PPARα, linking fatty acid oxidation and cellular senescence.
Abstract 14579: Predictors of In-Hospital Mortality in Coronary Artery Dissection Patients: An Insight From the National Inpatient Sample Database
Authors: Ghumman Ghulam Mujtaba , Shah Jay , Al-Dabbas Maen , Khan Muhammad Shayan , Luthra Kritika , Khan Amir , Ahsan Muhammad , Singh Heminder , Taleb Mohammed , Ali Sohail
Published: June 2023

Background:
There is a paucity of data on predictors of mortality in all-cause coronary artery dissection patients. The purpose was to study the baseline characteristics, associated co-morbidities, and in-hospital mortality in coronary artery dissection patients using the Healthcare Cost and Utilization Project National Inpatient Sample database.

Methods:
The Healthcare Cost and Utilization Project administrative longitudinal database contains encounter-level information on inpatient stays, emergency department visits, and ambulatory surgery in all U.S. hospitals. We performed a cross-sectional analysis on 25005 patients diagnosed with coronary artery dissection during hospitalization from January 2016 to December 2018. The primary outcome was in-hospital mortality.

Results:
Of the total patient population, 25005 patients were found to have coronary artery dissection. All patients with ages ≥ 18 were included in the study (24980). The observed overall in-hospital mortality was 6.0% (1498 patients out of 24980). The higher mortality was observed in age group >80 years when compared to the age group <40 years (adjusted odds ratio: 8.5; 95% confidence interval: 5.7 to 12.4; p-value < 0.01). Patients with peripheral vascular disease (adjusted odds ratio: 2.0; 95% confidence interval: 1.7 to 2.3; p-value < 0.01) and cardiogenic shock (adjusted odds ratio: 10.8; 95% confidence interval: 9.5 to 12.2; p-value < 0.01) showed higher mortality (Table 1,2).

Conclusion:
To the best of our knowledge, this is the largest population-based study investigating the predictors of in-hospital mortality in all-cause coronary artery dissection patients. Our analysis showed higher mortality with increasing age and in patients who developed cardiogenic shock and those with peripheral vascular disease.
Abstract 14581: Massive Sinus of Valsalva Aneurysm With Rupture Into the Right Atrium
Authors: Khludenev George , Rajendran Iniya , Ibrahim Ramzi , Acharya Tushar , Lee Kwan Seung S , Corban Michel , Insel Michael , Seckeler Michael D , Rischard Franz , Kubba Saad
Published: June 2023

Case Presentation:

A 40-year-old male presented with decompensated heart failure and severe pulmonary hypertension (echo-predicted right ventricular systolic pressure 60 mmHg). Right heart catheterization revealed high output heart failure (cardiac index 7.3 L/min/m
2
), left to right shunt (Qp:Qs 3.6:1), pulmonary hypertension (mean 38 mmHg), and normal pulmonary resistance (1.53 Wood units). Transesophageal echocardiogram revealed a large non-coronary sinus of Valsalva aneurysm with communication to the right atrium (Figure 1a and b). Percutaneous transcatheter closure of the aneurysm was deferred due to large size (3.3 x 4.3 cm), proximity to the right coronary artery, and risk of aneurysm rupture with catheter manipulation (Figure 1c). The patient underwent surgical aneurysm resection and aortic root replacement and recovered well.

Discussion:

Sinus of Valsalva aneurysms (SVAs) are rare pathologies characterized by expansion of the aortic root wall between the sinotubular junction and the aortic valve annulus and are often associated with connective tissue disorders. SVAs are often diagnosed incidentally on imaging but can present with symptoms if they rupture into nearby cardiac structures, such as an aorto-atrial fistula with left to right shunting, high output heart failure and hemodynamic compromise, as in this case. While transthoracic echocardiogram is the diagnostic modality of choice for most SVAs, multimodality imaging, catheterization, and advanced imaging may also be needed. Surgical repair remains the gold standard of therapy, however treatment with transcatheter device placement has also been successfully performed.
Abstract 14587: Dysregulation of Vascular Autophagy by Overexpression of p25/CDK5 is Associated With Vascular Senescence
Authors: Mondaca Ruff David G , Kim Ji Yong , Singh Sandeep , Wang Yu
Published: June 2023

Introduction:
Cardiovascular diseases are the main causes of death worldwide. These diseases are often associated with cardiovascular aging. Autophagy is a degradative cellular process that has been implicated in aging regulation. Cyclin-dependent kinase 5 (CDK5), which is normally activated by its regulatory subunit p25, has been implicated in several diseases. However, the role of p25/CDK5 signaling pathway in cardiovascular diseases and autophagy have not been fully understood.

Hypothesis:
Upregulation of vascular p25/CDK5 signaling pathway modifies autophagy induction and participates in vascular senescence.

Methods:
Selective overexpression of p25 (CDK5 activator) in the vascular endothelium was generated in a transgenic mouse model (EC-p25). Then, aortas from 30-weeks old EC-p25 and control mice were collected. Vascular senescence was evaluated with senescence-associated β-galactosidase (SA-β-gal) staining. Protein levels were measured by Western blotting. Primary porcine aortic endothelial cells (PAECs) were transfected with pcDNA, p25 and CDK5. Autophagy activity, autophagic flux, cell death, and senescence were evaluated. A p-value of p<0.05 was considered as statistically significant.

Results:
EC-p25 mice exhibited increased SA-β-gal staining compared to the Control mice suggesting accelerated aging in the aorta. EC-p25 mice showed increased levels of autophagy compared to the Control mice. On the other hand, overexpression of CDK5 increased cell death, endothelial senescence, autophagy and proteins involved in autophagy induction in PAECs.

Conclusion:
Accelerated premature vascular aging induced by selective overexpression of the p25/CDK5 signaling pathway in the vascular endothelium may be associated with increased vascular senescence in the aorta by modifying autophagy activity and induction process.
Abstract 146: Risk Factors For Early Mortality After Fall From Height In An Urban Area
Authors: OZGULER ANNA , Gille Arnaud , Giorgetta Valentine , Baer Michel , Loeb Thomas
Published: June 2023

Introduction:
Death after falls from height are relatively common in urban areas. However, risk factors for early mortality are not clearly established, even fall height is still debated. The aim of this study was to identify risk factors for death on scene, after fall from a height, in patients aged 16 and over.

Method:
An Emergency Medical Service’s (EMS) database was used, it included all Advanced Life Support interventions. This EMS was located in an urban area with 300,000 inhabitants. All patients aged 16 and over, who fell from a height over 6.6 feet, between 2003 and 2018, were included. Age, gender, cause of fall (suicide or accidental), height of fall, landing surface (hard or soft), how the body hit the ground (headfirst landing or other), Index Severity Score (ISS) and initial Glasgow Coma Score (GCS) were collected. A backward stepwise logistic regression was used with occurrence of death on site as main outcome.

Results:
Six hundred and eighteen patients were included. The average age was 43.5 years (min 16-max 102) and sex ratio 2. Forty-eight percent were suicides. The average fall height was 36 feet (SD ± 35). The landing surface was hard in 51% of cases and landing was on head in 6%. The average ISS was 32 (SD ± 29.5) and mean GCS was 10 (SD ± 5.6). One hundred and ninety two (31%) patients died on scene. Results of the final logistic regression model are in table 1.

Conclusion:
In this study, age over 60, head first landing, suicide attempt, height of fall over 33 feet and hard landing surface, were significantly associated with on scene mortality after fall from height. Suicide prevention is one obvious way to reduce mortality from falls from heights.
Abstract 14608: QRS Voltage in Lead V1 After Cardiac Resynchronization Predicts Survival in Patients With Left Bundle Branch Block
Authors: Zehan Iulia G , Eotvos Csilla A , Coseriu Giorgia , Andrei Mihai , Schiop-Tentea Calina P , Porca Adriana , Blendea Dan
Published: June 2023

Introduction:
The QRS complex on the electrocardiogram is a reflection of the summation of instantaneous electrical forces within the heart. In left bundle branch block (LBBB), the propagation of the electrical wavefront is dyssynchronous and unopposed and is thereby associated with an increase in the QRS voltage in precordial leads like lead V1, which are closer to perpendicular to the direction of propagation.

Hypothesis:
The aim of this study was to assess the impact of cardiac resynchronization therapy (CRT) on QRS morphology and voltage in lead V1, and its ability to predict response.

Methods:
The study included 103 consecutive patients with LBBB (age 69±12 years, 80 men, left ventricular ejection fraction 22±6%, QRS width 159±22ms), who received CRT for a median duration of 42 months (IQR 28-53 months).

Results:
During follow-up 18 patients died. Total QRS amplitude in lead V1 decreased significantly from 1.4±0.9mV at baseline to 0.8±0.5mV post CRT, (P value = 0.0002), the decrease being more pronounced in patients who survived when compared to nonsurvivors (0.8±0.9mV vs. 0.3±0.9mV P value= 0.021). The algebric sum of the positive and negative deflections of the QRS complex in V1 (sumQRS
V1
) changed significantly from -1.4±0.7mV at baseline to -0.05±0.7mV post CRT (p value <0.0001). Patients who survived had a more negative sumQRS
V1
post CRT than nonsurvivors (-0.2±0.6mV vs +0.4±0.5mV p value=0.0012), and the sumQRS
V1
cutoff that best separated survivors from non-survivors was +0.3mV. Patients with sumQRS
V1
< 0.3mV had a significantly better survival than patients with sumQRS
V1
≥0.3mV (Figure). A >50% decrease in QRS amplitude in V1 with CRT, and sumQRS
V1
post CRT <0.3mV independently predicted event free survival in a multivariate Cox regression model that included age, gender, baseline left ventricular ejection fraction and the change in QRS duration.

Conclusions:
Changes in QRS voltage in lead V1 after CRT predict survival in patients with LBBB.
Abstract 14609: Exposure to Any Hospitalization and Specific Invasive Procedures Post Open Heart Valve Surgery Increases the Risk of Endocarditis
Authors: Kwan Timothy N , Chow Vincent , Brieger David , Sy Raymond , Kritharides Leonard , Ng Austin
Published: June 2023

Introduction:
Infective endocarditis (IE) after cardiac valve surgery is associated with high morbidity and mortality. Nosocomial exposure is a growing cause of IE in general. We investigated the risk of post valve surgery endocarditis (PVE) in patient who had any hospitalization and specific nosocomial exposures after open heart valve surgery.

Methods:
We identified all ≥18yo patients who had their first open heart cardiac valve surgery between 2001-2017 in New South Wales, Australia from the Admitted Patient Data Collection (APDC) registry. Patients with prior/current IE diagnosis at time of index valve surgery were excluded. Follow up was until 31 Dec 2018 with mortality and morbidity tracked from the respective death and APDC registries. Analyses based on Cox regression modelling included age, sex, background diagnoses and features of index valve surgery as time independent covariates, with any hospitalization (separately for specific invasive procedures) post index valve surgery as time dependent exposure covariates for risk of PVE within 6 months of exposure.

Results:
In total 23747 patients (median age [IQR] 73yo [65-79yo, 63% male) had cardiac valve surgery: 60% isolated aortic valve (n=15065), 28% isolated mitral valve (n=6702), 10% multiple valves (n=2385) and 1.5% right sided valves (n=357). 5.4% (n=1293) of patients experienced PVE at a median 2.9 years (IQR 0.7-6.2) after index valve surgery, with 65% (n=838) occurring within 6 months of any hospitalization. Any hospitalization exposure was associated with an adjusted hazard ratio of 4.0 for developing PVE (95% confidence interval 3.5-4.5). In addition, specific invasive procedures including repeat valve surgery were associated with an elevated risk for PVE (Figure).

Conclusions:
PVE is significantly more common after any hospitalization with specific invasive procedures carrying differential risk. Care should be taken to avoid unnecessary hospitalizations and procedures in these patients.
Abstract 14612: The Relationship Between Left Ventricular Geometry and Respiratory Sinus Arrhythmia in Patients With Vasovagal Syncope
Authors: Coseriu Giorgia , Eotvos Csilla Andrea , Zehan Iulia , Tentea Patricia C , Andrei Mihai G , Blendea Dan
Published: June 2023

Introduction:
The study was prompted by our observation that a significant number of patients with vasovagal syncope (VVS) have marked respiratory sinus arrhythmia as well as thin left ventricular (LV) walls. We hypothesized that the geometry of the LV walls may play a role in the pathogenesis of VVS.

Hypothesis:
The aim of this study was to assess LV geometry in relationship to respiratory sinus arrhythmia in patients with VVS

M
ethods:
We included 191 patients (age 52±20 years, 101 women) with VVS who had either a positive or negative response to tilt table testing TTT (n=64 TTT+, and n=127 TTT-). The VVS group was compared to a group of 75 patients with no syncope (NL) and similar age, sex and BMI distributions. Standard 12-lead electrocardiograms (ECG), vectorcardiograms, and transthoracic echocardiograms were performed to assess electrical activation as well as ventricular geometry and function. The magnitude of respiratory sinus rhythm arrhythmia was measured as the maximum percent change in RR interval on a 10 second 12-lead ECG (dRR) performed before the TTT.

Results:
When compared to NL group patients with VVS had significantly higher dRR and LV end diastolic diameter (12 ±8% vs 10±8%, p=0.047 and 44±5 vs 46±6mm p=0.006 respectively) The end-diastolic thickness of the interventricular septum (IVS) and that of the LV posterior wall (PWT) in the VVS group were significantly smaller than in the NL group (8.9±1.7mm vs 9.6±1.8mm p value=0.003 and 8.4±1.5mm vs 9.2±1.6mm p value=0.0002). The magnitude of respiratory sinus arrhythmia expressed as dRR correlated inversely and significantly with IVS (r=-0.32; p value=0.042). The was however no significant correlation between dRR and PWT. These results suggest that a more pronounced respiratory sinus arrhythmia could be related to more ample variations in right and left ventricular filling due to increased ventricular interdependence via a thinner and more compliant ventricular septum.

Conclusions:
The geometry of the LV as well as the cardiovascular impact of respiratory movements may play a role in the pathogenesis of VVS.
Abstract 14621: The Endothelial Lipase Loss of Function Mutation R450G Causes Hyperalphalipoproteinemia That Does Not Protect Against ASCVD
Authors: Jaafar Ali K , Lambert Gilles
Published: June 2023

Background:
High-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk are inversely related in epidemiological studies. However, some rare monogenetic mutations that raise HDL do not appear to confer atheroprotection.

Methods:
The
LIPG
gene, encoding Endothelial Lipase (EL), was sequenced in 337 patients with hyperalphalipoproteinemia (HDL-C>80mg/dL) for whom a causative variant in other genes affecting plasma HDL levels (
CETP, APOA1, ABCA1, LCAT, LPL, GALNT2
) had been excluded. HDL particle size distribution was determined using a Lipoprint HDL subtraction test and further assessed by non-denaturing gradient gel electrophoresis followed by densitometric scanning. EL variants were cloned by site directed mutagenesis, expressed in HEK293 cells and compared to wild-type EL. Their expression in cell extracts and secretion in culture medium were measured by western-blot and ELISA. EL phospholipase enzymatic activity was assessed by measuring the production of non-esterified free fatty acids (FFA) using native and reconstituted HDL (rHDL) as substrates.

Results:
We identified the novel EL R450G missense mutation in three individuals (2 heterozygotes and one homozygote). Their HDL particles were larger than those of normolipemic controls (66±14% vs. 36±6% of large HDL1 particles; P=0.02). Six week treatment with Probucol 1g/day reduced the amount of HDL1 in those patients. Despite elevated circulating HDL levels, these patients presented with atherosclerotic cardiovascular disease. In vitro, the R450G variant was expressed and secreted normally from cells but displayed markedly reduced enzymatic activity compared with wild-type EL (Vmax = 6±4, vs. 32±5 nmol/Hr and Km = 0.01±0.07 vs. 0.30±0.15 mM, respectively; P<0.01, all).

Conclusion:
EL-R450G is a loss-of-function variant associated with hyperalphalipoproteinemia. Carriers of this mutation do not appear to be protected against atherosclerosis.
Abstract 14625: Strategies for Maturation of Cardiovascular Organoids for Modeling Acquired and Inherited Adult-Onset Cardiomyopathies
Authors: Kazma Noam , Haiim Idan , Bashai Caroline , Nevo Anastasia , Libai Yaara , Caspi Oren
Published: June 2023

The development of Induced Pluripotent Stem cells (iPSC) technology has provided a lot of opportunities for disease modeling and cardiovascular regeneration. Two leading limitations of most iPSC-based modeling systems are: the relatively immature phenotype of the generated cardiomyocytes (CMs) (which exhibit fetal-like characteristics and fail to fully emulate the physiology processes of adult myocardium); and the lack of multicellularity (supporting cells such as endothelial cells, cardiac fibroblasts, and smooth muscle cells) facilitating the function of the organoid as an authentic cardiac tissue.The current project aims at engineering mature cardiovascular organoids for modeling acquired and inherited cardiomyopathies left ventricular hypertrophy and inherited hypertrophic cardiomyopathy. The expression of cardiac Troponin I (TnI) isoform 3 is the hallmark of sarcomere maturation.The study planned will be conducted using an iPSC tissue culture system. Cell and tissue maturation was evaluated at the morphological level by confocal microscopy, at the molecular level by RT-qPCR and western blot analysis, and at the functional level by force generation and calcium imaging. Engineered cardiovascular organoids are evaluated by a tailor-made high-throughput robotic system allowing to measure electrophysiological signals. Initial Results: CMs maturation inducing strategies have been implicated by combining metabolic maturation together with factors associated with robust maturation (mTOR inhibitor, hormonal supplements, and steroids). The strategy used resulted in significant maturation as evaluated by molecular markers (significant induction of TNNI3 levels) and physiological ones (shorter contraction duration, relaxation time, and time-to-peak). In addition, protocols for simultaneous maturation of CMs together with endothelial cells, cardiac fibroblasts, and smooth muscle cells have been developed.The project suggested providing a unique opportunity to establish cardiovascular organoid-based platforms for modeling acquired and inherited adult-onset cardiomyopathies. The platform may be used for gaining mechanistic insights, toxicity screening, and target identification as well as drug discovery.
Abstract 14632: Enhanced Therapeutic Effect on Myocardial Infarction by Using Thick and Viable iPSC Derived Cardiac Tissue
Authors: Li Junjun , Qu Xiang , Li lingjun , HUA YING , zhang jingbo , Kawamura Takuji , Matsuura Ryohei , Sougawa Nagako , Ito Emiko , Mochizuki-oda Noriko , Harada Akima , Sawa Yoshiki , LIU Li , Miyagawa Shigeru
Published: June 2023

Introduction:
Human iPSC derived cardiomyocytes (iPSC-CMs) have been proved to be a promising method to treat the heart failure. Multiple clinical studies including one in our group are ongoing around the world. Due to the diffusion limit, so far it is difficult to prepare viable cardiac tissue with high thickness. We hypothesized that by using multilayer fiber sheets and enhanced perfusion system, viable and thick cardiac tissue could be obtained for improved therapeutic effect for treating myocardial infarction.
Method and Results:
PLGA fiber sheet with multilayer and high porosity (30.61% ± 1.85%, n = 4) was fabricated for iPSC-CMs penetration and organization. A low-shear stress perfusion system was developed to promote the oxygen diffusion in the thick tissue. At day 5, multilayer cardiac tissue showed compact structure with thickness of 878.64 ± 193.45 μm (n = 4) and viability of 85.32 % ± 6.75 % (n = 4). Compared with the single layer tissues, the multilayer cardiac tissues demonstrated improved contractile properties and secretion of angiogenesis factors: VEGF, HGF and TGF-β1. When used for treating rat with myocardial infarction, multilayer group showed significantly improved left ventricular ejection fraction (0 vs. 4 week: 39.1 ± 4.6 % vs. 52.3 ± 7.8 %, n=8, p = 0.0029), whereas the control group showed no significant change (0 vs. 4 week: 40.6 ± 5.4 % vs. 44.9 ± 4.1 %, n=8, p = 0.37). The staining on sliced heart confirmed the survival of transplanted cells in large area. Moreover, the multilayer group showed significantly lower fibrosis at the border zone than the control group (10.8 % ± 3.1 % vs. 16.4 % ± 5.9 %, n=7, p=0.024). There are no significant differences in cell diameter and capillary density in border zone between two groups. Both groups showed no significant inflammatory reactions (CD68).

Conclusion:
By using multilayers fiber sheet and enhanced perfusion system, viable and thick iPSC-cardiac tissue could be obtained with enhanced features over the single layer cardiac tissue such as contractility and secretion. While used for transplantation, the multilayers cardiac tissue demonstrated improved therapeutic effect for treating myocardial infarction, holding high potential for future clinical applications.
Abstract 14652: Inherited Genetic Variants in Inflammatory Genes Modulate the Increased Mortality Risk in Patients With HFrEF and Clonal Hematopoiesis
Authors: Cremer Sebastian , Katsaouni Nikoletta , Abplanalp Wesley , Berkowitsch Alexander , Kirschbaum Klara , Rieger Michael , Rapp Steffen , Wild Philipp , Dimmeler Stefanie , Schulz Marcel , Zeiher Andreas M
Published: June 2023

Aims:
Clonal hematopoiesis (CH) was shown to be associated with increased mortality in patients with ischemic heart failure with reduced ejection fraction (HFrEF). Mechanistically, circulating monocytes of mutation carriers display increased expression of proinflammatory genes. Inherited genetic variants (SNP) in the IL-6 pathway are well known to affect inflammatory activation. Therefore, we investigated whether known SNPs in genes encoding for components of the inflammasome/IL-6 signaling pathway modulate fatal outcomes in HFrEF patients with CH.

Methods and Results:
In a total of 446 patients with chronic HFrEF, blood or bone marrow cells were analyzed for the CH mutations DNMT3A and TET2 as well as 48 preselected SNPs affecting genes in the NLRP3 inflammasome/IL-6 signaling pathway. The 103 patients carrying a CH driver mutation demonstrated significantly increased mortality compared to the 343 patients without CH mutations (p=0.0064). We identified three commonly occurring variants known to disrupt IL-6 signaling (rs2228145, rs4129267 and rs4537545), which abrogated the increased mortality risk in patients with HFrEF and CH (p≤0.05 for each SNP). On the contrary, three different SNPs (rs2250417, which is associated with increased IL-18 levels; rs4722172 and rs4845625, which are known to activate IL-6 signaling) were identified to mediate fatal outcomes in patients with HFrEF and CH (p<0.05 for each). sc RNA-sequencing of circulating monocytes of patients with HFrEF revealed increased inflammatory signaling in DNMT3A mutation carriers harboring IL6/IL18 activating SNPs.

Conclusion:
Inherited variants in loci encoding for genes involved in inflammatory signaling interact with mortality risk in HFrEF. These data provide mechanistic insights into inflammatory mechanisms contributing to fatal outcomes of HFrEF in CH carriers, but may also inform trials evaluating precision-targeted therapy in those patients.
Abstract 14664: Heart Failure as the Cancer for the Heart: The Prognostic Role of the New HLM Score
Authors: Severino Paolo , D'Amato Andrea , Mariani Marco Valerio , Prosperi Silvia , Alunni Fegatelli Danilo , Birtolo Lucia Ilaria , Costi Bettina , Angotti Danilo , Cerrato Enrico , Lavalle Carlo , Maestrini Viviana , Pizzi Carmine , Foà Alberto , vestri annarita , Palazzuoli Alberto , Mather Paul J. , Casale Paul N. , Mancone Massimo , Fedele Francesco
Published: June 2023

Introduction:
The multiorgan involvement of heart failure is similar to the spread observed in cancer. We proposed a new score system, named HLM, analogous to TNM classification used in oncology. HLM refers to (i) H: heart damage, instead of “T” for tumor; (ii) L: lung involvement, instead of “N” for lymph nodes; (iii) M: involvement of peripheral organs, instead of “M” for metastasis.

Hypothesis:
to compare HLM score to NYHA class, ACC/AHA stages and HF classification by left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients.

Methods:
We performed a multicentric, observational, prospective study of consecutive patients admitted for HF, or at risk for HF. All parameters for heart, lungs and organs’ function were collected. HLM score, made up of 4 stages of severity, was built starting from HLM classification. Each patient was classified according to HLM, NYHA, ACC/AHA stages and LVEF. The primary composite endpoint was all-cause death and rehospitalization due to HF; patients were followed up for 12 months.

Results:
We enrolled 1720 patients who completed the 12-months follow-up. As showed by Kaplan Meier curves, HLM was the most accurate score to predict primary endpoint at 12 months. The area under the ROC curve (AUC) was greater for HLM score than NYHA, ACC/AHA stages and LVEF classification, regarding the composite endpoint (HLM=0.645; NYHA=0.580; ACC/AHA=0.572; LVEF=0.572). HLM score related AUC showed statistically significant differences compared to LVEF (p=0.002), ACC/AHA (p=0.002) and NYHA (p=0.009).

Conclusions:
HLM score has a greater prognostic power compared to other nosologies, in terms of the composite endpoint of all-cause death and rehospitalization, at 12 months follow up.
Abstract 14688: Identification of Patients With Atrial Fibrillation Using an Electrocardiogram in Sinus Rhythm: External Reproduction and Validation of a Deep Neural Network Algorithm
Authors: Gruwez Henri , Barthels Myrte , Pison Laurent , Nuyens Dieter , vandervoort pieter , Pierlet Noëlla
Published: June 2023

Introduction:
Atrial fibrillation (AF) can occur asymptomatically and can only be diagnosed while the arrhythmia is present. Hence, it is underdetected. An artificial intelligence (AI) algorithm has been developed by Attia et al. to identify patients with AF based on a 12-lead electrocardiogram (ECG) in sinus rhythm (SR). We aim to reproduce these findings in an unrelated patient population and unrelated clinical center using the same deep neural network (DNN) architecture.

Methods:
All patients older than 18 years with at least one ECG in SR performed at our center between 10/1/2002 and 8/31/2022 were included in the study. Diagnostic labels were given by the GE-Marquette ECG system. For patients without an ECG in AF, all ECGs in SR were included. For patients with one or more ECGs in AF, all ECG in SR starting 31 days before the AF event were included. The ECGs were randomly allocated to a training, internal validation, and testing dataset in a 7:1:2 ratio. A DNN following the architecture of Attia et al. was trained to discriminate between patients with and without AF.

Results:
The dataset consisted of 494.042 ECGs in SR from 142.310 patients. AF was diagnosed in 8.9%. Testing the model on the first ECG of each patient (main analysis) resulted in a sensitivity of 78.9% (95% CI, 77.6 - 78.5), specificity of 78.0% (95% CI, 77.5 - 78.5), accuracy of 78.1 (95% CI, 77.6 - 78.5), area under the receiver operating curve (AUC) of 0.87 (95% CI, 0.86 - 0.87), and F1 score of 39.3% (95% CI, 38.1 - 40.6). Testing the model on all ECGs in the first 31 days and selecting the maximum probability of AF (secondary analysis) increased the sensitivity to 81.1 (95% CI, 78.4 - 83.7), specificity to 79.8 (95% CI, 79.3 - 80.3), accuracy to 79.8 (95% CI, 79.4 - 80.3), AUC to 0.88 (95% CI, 0.87 - 0.89), but lowered the F1 score to 20.8% (95% CI, 19.51 - 22.0).

Conclusion:
An AI-enabled ECG algorithm for the identification of patients with AF on a SR-ECG can be reproduced with external data in an external center at clinical grade accuracy.
Abstract 14691: Sex Differences in the Prognostic Value of N-Terminal Brain Natriuretic Peptide in Pulmonary Arterial Hypertension
Authors: Van Wezenbeek Jessie , Llucia-Valldeperas Aida , Smal rowan , Bekedam Fjodor T , Vonk Noordegraaf Anton , Goumans Marie Jose , Bogaard Harm J , De Man Frances S
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) causes right heart failure (HF) and mainly affects females, but males have worse survival. Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), along with N-terminal BNP (NTproBNP), are secreted from cardiomyocytes upon stretch and are important biomarkers in HF. Sex differences are observed in NTproBNP levels and prognostic value in left HF, but unknown in right HF. The aim was to assess sex differences in NTproBNP levels and prognostic value in PAH from a translational perspective.

Methods:
We screened patients with baseline NTproBNP measurements and right heart catheterization between 2002 and 2020. Induced pluripotent stem cells (iPSCs) from 1 male and 1 female PAH-patients were differentiated into cardiomyocytes (iPSC-CMs), and stretched for 24h at 1Hz and 10% on the Flexcell FX-6000 system (N=2). Gene expression analyses were performed on static and stretched samples.

Results:
266 patients (N=106 male, N=166 female) were included. Median baseline NTproBNP levels were similar in male and female patients (1118
vs
832 ng/ml, P=0.58). We risk stratified patients on NTproBNP according to the guidelines and assessed differences in 1-year survival. In males highest 1-year mortality was observed in low and low-intermediate risk groups (16,4% and 7.7%, respectively)
vs
females (4.7% and 4.2%, respectively) (Figure1 A,B). Preliminary results indicate ~2x higher BNP mRNA expressions on male
vs
female patients (0.80
vs
0.37, N=3 male and N=3 female, P=0.018), after mechanical stretch (Figure1 C).

Conclusions:
Although no sex differences were observed in NTproBNP plasma levels, it had different prognostic value in male and female patients. Furthermore,
in vitro
male iPSC-CMs had higher BNP levels after stretch compared to female iPSC-CMs.