bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13091: Relaxation and Calcium Cycling in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction
Authors: Runte K. E , Bell Stephen , Selby Donald E , LeWinter Martin M , Palmer Bradley M , Meyer Markus F
Published: April 2024

Prolonged myocardial relaxation is believed to play an important role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). An impairment of cellular Ca
2+
extrusion in diastole may contribute to this delay in relaxation. We investigated relaxation characteristics and cellular Ca
2+
- and Na
+
-handling in intact, contracting myocardial strip preparations dissected from epicardial biopsies obtained from patients with hypertensive heart disease (HHD) with and without HFpEF. Relaxation time parameters (at rates of 60/min and 180/min), cellular Ca
2+
- (Fura-2) and Na
+
- (ANG-2) cycling were studied in 20 patients with HHD without HFpEF (HHD), 12 with HHD and HFpEF (HHD(+)HFpEF) and 26 without HHD or HFpEF, who served as referent controls (CTR). Expression levels of key ion transporters were also measured. Since Ca
2+
-handling can be pharmacologically modified, we evaluated the therapeutic potential of the Na
+
-influx inhibitors ranolazine (10μM), furosemide (50μM) and amiloride (50μM) to accelerate relaxation. Compared with controls, the time to half maximal relaxation at 60/min was prolonged in both HHD and HHD(+)HFpEF (CTR: 263±5ms, HHD: 295±12ms, HHD(+)HFpEF: 296±11ms; p=0.01 and p<0.01, respectively). When the stimulation rate was increased to 180/min, this prolongation resulted in incomplete relaxation manifested as increased diastolic force in both HHD (26±3%, p=0.01) and HHD(+)HFpEF (33±9%, p=0.01). This finding was associated with an increase in diastolic Ca
2+
(Fura-2: 28±6%; p<0.01) and a minor increase in Na
+
(ANG-2: 0.5±0.2%; p=0.05). Expression levels of Ca
2+
- and Na
+
-handling proteins were not different between the groups. None of the pharmacologic agents accelerated relaxation or improved incomplete relaxation at high heart rates. We conclude that relaxation is prolonged in isolated myocardium from patients with HHD and HHD(+)HFpEF. An impairment of diastolic Ca
2+
removal appears to play a role in incomplete relaxation at higher heart rates. This functional deficit is not due to changes in expression levels of key transporters or regulatory proteins and was not improved by pharmacologic inhibition of Na
+
-influx.
Abstract 13099: Geriatric Nutritional Risk Index Predict Cardiovascular Events in Patients With Pheripheral Artery Disease
Authors: Minamisawa Masatoshi , Miura Takashi , Motoki Hirohiko , Ueki Yasushi , Mochidome Tomoaki , Oguchi Yasutaka , Nishimura Hitoshi , Ebisawa Soichiro , Koyama Jun , Ikeda Uichi
Published: April 2024

Introduction:
Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool for elderly patients. Lower GNRI is associated with a worse prognosis in patients with critical limb ischemia or hemodialysis. However, few data are available regarding the prognostic impact of GNRI value for risk stratification in patients with peripheral artery disease (PAD).

Hypothesis:
We hypothesized that GNRI values would predict adverse cardiovascular (CV) events in patients with PAD.

Methods:
We retrospectively enrolled 480 consecutive patients with PAD who were hospitalized for CV diseases between 2005 and 2012. GNRI on admission was calculated as follows: 14.89 * serum albumin (g/dL) + 41.7 * body mass index/22. Patients were divided into two groups stratified by GNRI (median value 103.3). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, and stroke.

Results:
Over a 3.7-year median follow-up, adverse events were observed in 164 patients (34.2 %). In Kaplan–Meier analysis, patients with low GNRI (< 103.3, n = 239) showed worse prognoses than those with high GNRI (≥ 103.3, n = 241) (MACE incidence 42.7 % vs. 25.7 %, P < 0.001). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, estimated glomerular filtration rate, B-type natriuretic peptide, and left ventricular ejection fraction, Low GNRI (<103.3) was significantly associated with the incidence of MACE (hazard ratio: 2.14, 95% confidence interval: 1.34–3.41; P < 0.001).

Conclusions:
In patients with PAD, GNRI is an independent predictor of MACE. Simple assessment of GNRI may be useful for predicting CV events in those patients.
Abstract 13144: MicroRNA Sequencing Highlights Regulatory Networks Upstream of Osteopontin and B-type Natriuretic Peptide in Acute Coronary Sydrome
Authors: Kwee Lydia C , Grass Elizabeth , Neely Megan L , Gregory Simon G , Haas Joseph V , Laska Dennis A , Kowala Mark , Michael Laura F , Wetterau John R , Duffin Kevin L , Roe Matthew , Ohman E. M , Fox Keith A , White Harvey , Armstrong Paul , Chan Mark Y , Shah Svati H
Published: April 2024

Introduction:
The genomic regulatory networks underlying the pathogenesis of acute coronary syndrome (ACS) are incompletely understood. As intermediate traits, circulating protein biomarkers report on underlying disease severity and are powerfully prognostic in ACS. We hypothesized that integration of dense microRNA (miRNA) profiling with measurement of biomarkers would highlight potential regulatory pathways.

Methods:
We studied 186 patients enrolled in the biomarker substudy of the TRILOGY clinical trial of ACS. MiRNA sequencing was performed on RNA extracted from whole blood, and seven known prognostic protein biomarkers were measured from plasma (N-terminal pro B-type natriuretic peptide [NT-proBNP], C-reactive protein, osteopontin [OPN], myeloperoxidase, growth differentiation factor 15, monocyte chemoattractant protein 1, and neopterin). MiRNAs were tested for association with these biomarkers using generalized linear models. Target genes putatively regulated by the associated miRNAs were examined using pathway analysis.

Results:
Fourteen miRNAs, including cardiac-related miRs 20b-5p and 320a,b and d, were associated with OPN levels (min. p=1.1x10
-4
), and five miRNAs, including cardiac-related miRs 25-3p and 423-3p, were associated with NT-proBNP levels (min. p=3.4x10
-4
); no other biomarkers showed significant associations. Sixty-three KEGG pathways were enriched in the target genes of either NT-proBNP- or OPN-associated miRNAs, with five pathways found in the top ten for both biomarkers: prion diseases, fatty acid biosynthesis, lysine degradation, protein processing in endoplasmic reticulum, and viral carcinogenesis.

Conclusions:
By integrating large-scale microRNA profiling with circulating biomarkers as intermediate traits, we identified associations of known cardiac-related and novel miRs with two prognostic biomarkers (OPN and NT-proBNP), and identified potential genomic regulatory networks underlying these biomarkers. We further identified novel non-cardiac genomic pathways associated with these biomarkers. These results may inform future studies delineating genomic pathways underlying ACS outcomes.
Abstract 13145: Ventriculoarterial Coupling Ratio is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot
Authors: Godfrey Max E , Geva Tal , Sleeper Lynn A , Lu Minmin , Valente Anne Marie , Prakash Ashwin
Published: April 2024

Introduction:
Patients with repaired tetralogy of Fallot (TOF) are at risk of premature death and ventricular arrhythmias. The ventriculoarterial coupling (VAC) ratio, the ratio of arterial elastance (Ea) and ventricular end-systolic elastance (Ees), is a measure of cardiac efficiency. Little is known about the VAC ratio in this population. We used a previously described cardiac magnetic resonance (CMR) method to measure right and left VAC ratios in patients with repaired TOF, and assessed the hypothesis that this is related to outcomes.

Methods and Results:
We measured VAC from CMR data at a single institution on 593 TOF patients (age 21.5 ± 14.4 years) and 58 controls (age 13.2 ± 4.0 years). Frequency matching based on age and gender yielded 326 TOF patients to compare with controls. VAC ratio was calculated for both right (RV) and left (LV) ventricles as Ea/Ees = end-systolic volume/stroke volume. TOF patients had higher RV and LV VAC ratios (p<0.001) (RV results, figure A). Within the TOF cohort, RV VAC ratio correlated positively with LV VAC (r=0.43, p<0.001), but not with pulmonary regurgitation fraction. After a median follow-up of 5.0 (IQR 2.4-8.5) years, 26 patients (4.4%) reached a composite endpoint of death (n=16), aborted sudden cardiac death (n=5), or sustained ventricular tachycardia (VT, n=5). An RV VAC ratio in the highest tertile (T3) was associated with higher risk of the outcome (p<0.001, figure B). Controlling for known risk factors (RV mass-to-volume ratio, atrial arrhythmia and non-sustained VT), an RV VAC ratio ≥1.11 (highest tertile) was independently associated with the composite outcome (hazard ratio 7.3, 95% CI 2.7-19.9, p<0.001).

Conclusion:
In this cohort, TOF patients demonstrated inefficient VAC as compared with controls. A higher RV VAC ratio was independently associated with the composite outcome of death, aborted sudden cardiac death, or sustained VT. Further investigation of the significance of VAC in this population is warranted.
Abstract 13231: Atrial Fibrillation Recurrence After Catheter Ablation is Associated With Left Atrial Appendage Volume and Plasma Docosahexaenoic Acid Levels
Authors: Shiozawa Tomoyuki , Shimada Kazunori , Sekita Gaku , Miura Seiji , Tabuchi Haruna , Hayashi Hidemori , Al Shahi Hamad , Kadoguchi Tomoyasu , Sugita Yurina , Ouchi Shohei , Aikawa Tatsuro , Takahashi Shuhei , Miyazaki Tetsuro , Fujimoto Shinichiro , Sumiyoshi Masataka , Nakazato Yuji , Daida Hiroyuki
Published: April 2024

Background:
Risk factors for atrial fibrillation (AF) recurrence in patients undergoing catheter ablation (CA) are unclear. We assessed whether left atrium (LA) and LA appendage (LAA) volume, cardio-metabolic markers such as oxidative and glycation stresses, endothelial function, and polyunsaturated fatty acids (PUFAs) levels were associated with AF recurrence.

Methods:
Seventy-seven consecutive patients with AF undergoing first-time CA (mean age, 59 ± 8 years; male, 81%; paroxysmal AF, 65%; chickenwing morphology, 49%) were enrolled. LA, LAA volume, and morphology were measured using 3D-computed tomography. Measurements of skin auto-fluorescence advanced glycation end-products (AGEs), circulating PUFAs, and vascular function using EndoPAT were performed immediately before CA.

Results:
Patients with AF recurrence (36%) had larger LAA volumes (19 ± 13 vs 14 ± 4 cm
3
, P = 0.04) and a larger LAA orifice area (4.9 ± 2.0 vs 3.2 ± 2.1 cm
2
, P = 0.001) than those without AF recurrence, whereas LA diameter and LA volumes were not significantly different. NT-proBNP levels were significantly higher in patients with AF recurrence (527 ± 604 vs 245 ± 268 pg/mL, P = 0.03) than in those without AF recurrence. Notably, AF recurrence occurred in all patients (n = 5) with giant LAAs (≥25 mL). There were no differences in AGEs or vascular function between patients with and without AF recurrence. LAA volume was significantly and negatively associated with docosahexaenoic acid (DHA) levels (P = 0.006,
r
= –0.32), and patients with giant LAAs (≥25 mL) had significantly lower levels of DHA than other patients (107 ± 36 vs 157 ± 46 μg/mL, P = 0.04). Multiple regression analysis determined that log NT-proBNP and plasma DHA levels were independent factors for LAA volume (P = 0.03, P = 0.02, respectively), when adjusted for age, left ventricular (LV) ejection fraction, LV diameter at end systole, AF detected age, log NT-proBNP, plasma EPA, and DHA levels.

Conclusions:
A large LAA volume and higher NT-proBNP levels were associated with AF recurrence after CA; AF recurred in all patients with giant LAAs (≥25 mL). Moreover, low levels of DHA were associated with a large LAA volume. Thus, the association between LAA volume and low plasma DHA levels may be an important factor for post-CA AF recurrence.
Abstract 13235: Enhanced Receptor-independent Nucleoside Diphosphate Kinase Mediated G
s
Protein Signaling Contributes to Arrhythmogenic Calcium Mishandling in Atrial Fibrillation
Authors: Schaefer Marina , Abu-Taha Issam , Naud Patrice , Qi Xiao Yan , Gundlach Vanessa , Kamler Markus , Wieland Thomas , Nattel Stanley , Dobrev Dobromir
Published: April 2024

Background:
Enhanced G-protein related cyclic AMP (cAMP) signaling and abnormal Ca
2+
handling due to dysfunctional ryanodine receptor type-2 (RyR2) are implicated in atrial fibrillation (AF). Nucleoside diphosphate kinase (NDPK) forms complexes with G
s
proteins, increasing cAMP signaling via receptor-independent G protein activation. Here, we studied the possible proarrhythmic role of NDPKs in clinical (chronic AF, cAF) and experimental AF.

Methods:
NDPK and G protein expression were assessed by immunoblotting in atria from sinus rhythm (Ctl) and cAF patients; dogs undergoing AF-mimicking tachycardia remodeling (ATR, 400 bpm, 7 days) or AF-promoting chronic atrial ischemia; and canine atrial cardiomyocytes (CMs) paced in vitro for 24-48 hrs at 1 (P1) or 3 Hz (P3). cAMP was measured by immunoassay. Immunostaining was used for protein visualization. Spontaneous sarcoplasmic reticulum (SR) Ca
2+
release events (SCaEs) in CMs overexpressing NDPKs or EGFP-control (adenoviral gene-transfer) were recorded with epifluorescence (Indo-1).

Results:
NDPK-B, NDPK-C, Gα
s
and Gβ
1
were upregulated in cAF patient atria (Fig A). ATR and chronic atrial ischemia increased NDPK-B expression in canine atria (Fig B). In vitro tachypacing reproduced AF effects on NDPK/Gα
s
in CMs (Fig C). Accordingly, cAMP levels were higher in cAF patients and P3-paced CMs (Fig D-E). Adenoviral NDPK-B and NDPK-C overexpression increased cAMP levels (Fig F). NDPK-B, NDPK-C and Gα
s
co-localized at the plasma membrane when upregulated by tachypacing canine CMs. SCaEs, a proarrhythmic consequence of diastolic SR Ca
2+
leak, were enhanced in NDPK-B or NDPK-C overexpressing CMs, and the latency from last regular SR Ca
2+
release was reduced (Fig G).

Conclusions:
Receptor-independent NDPK-mediated G
s
-protein/cAMP signaling is upregulated in clinical and experimental AF, causes arrhythmogenic SCaEs, and is likely a novel contributor to ectopy-inducing atrial triggered activity due to SR Ca
2+
leak.
Abstract 13260: Trends in Survival From In-hospital Cardiac Arrests During Nights and Weekends
Authors: Ofoma Uchenna R , Basnet Suresh , Berger Andrea , Kirchner H L , Girotra Saket
Published: April 2024

Background:
In-hospital cardiac arrest (IHCA) survival is worse during nights and weekends. Although survival and neurologic outcomes after IHCA have improved in recent years, it remains unknown whether the above trends are consistent in patients with IHCA during nights and weekends.

Methods:
We identified 151,071 adults at 470 U.S. hospitals in the Get with the Guidelines-Resuscitation registry during 2000-2014. Using multivariable logistic regression with generalized estimating equations, we examined temporal trends in survival to discharge and determined whether trends in IHCA differed during on-hours (Monday - Friday 7:00 am - 10:59 pm) vs. off-hours (Monday - Friday 11:00 pm - 6:59 am, Saturday-Sunday, all day). We also examined acute resuscitation and post-resuscitation survival as secondary outcomes.

Results:
Among 151,071 participants, 79,091 (52.4%) had an IHCA during off-hours. Risk-adjusted survival proportions improved over time in both groups (
on-hours
: 16.0% in 2000, 25.2% in 2014;
off-hours
: 11.9% in 2000, 21.9% in 2014; P for trend < .001 for both). However, temporal trends in survival did not differ between on-hours and off-hours both on absolute (P=0.75) and relative scale (P = .059, Table). Acute resuscitation survival improved significantly in both groups (
on-hours
: 56.1% in 2000, 71% in 2014;
off-hours
: 46.9% in 2000, 68.2% in 2014; P for trend < .001 for both) such that difference between on-hours and off-hours narrowed over time (P=0.02 absolute scale, P < .001 relative scale, Table). In contrast, although post-resuscitation survival improved over time in both groups (P for trend < .001), the absolute and relative differences persisted in both groups (Table).

Conclusions:
Despite a significant temporal reduction in acute resuscitation survival difference for IHCA during on-hours compared to off-hours, differences in overall survival persist between the groups, highlighting an important area for quality improvement.
Abstract 13264: Varying Ventilation Strategies During Cardiac Arrest Has Minimal Impact on Hemodynamics
Authors: Paradis Norman , Moodie Karen , Kaufman Christopher L , Lampe Joshua W
Published: April 2024

Introduction:
Prolonged duty cycle ventilation and hyperventilation are associated with reduced venous return during CPR. Meanwhile, the 30:2 compressions-ventilation method requires pauses in compressions, which could also negatively affect hemodynamics. We investigated the effect of varying ventilation strategies on hemodynamics in a swine model of cardiac arrest.

Hypothesis:
Continuous ventilations with a short duty cycle, as compared to longer duty cycles and standard 30:2 ventilation, would be associated with improvements in hemodynamics.

Methods:
CPR was performed on eight domestic swine (~30 kg) using standard physiological monitoring. Blood flow was measured in the inferior vena cava (IVC). Ventricular fibrillation (VF) was electrically induced. Mechanical chest compressions (CC) were started after four minutes of VF. CC were delivered at a rate of 100 compressions per minute and a depth of 2” for a total of 12 min. Animals were intubated and mechanically ventilated throughout the experiment. Three ventilation strategies were tested: 1) continuous ventilator-driven ventilation (CV-DV) at a rate of 6 breaths per minute and a 0.20 duty cycle, 2) CV-DV at a rate of 6 breaths per minute and a 0.50 duty cycle, and 3) standard 30:2 at a 0.20 duty cycle. All tidal volumes were calculated as 7 ml/kg. PEEP was set to zero for all ventilations.

Results:
Across 12 minutes of CPR, aortic pressure and coronary perfusion pressure was greater with CV-DVs of 0.20 and 0.50 duty cycle as compared to 30:2 (Table). Overall net flow in the IVC was not different among ventilation strategies.

Conclusions:
As compared to the 30:2 method, CV-DVs at 0.20 and 0.50 duty cycles produced small increases in blood pressures but no changes in venous return. Further research is needed to determine if hemodynamics can be improved by synchronizing continuous ventilations to CC and if this association reflects elimination of the interruptions in chest compressions.
Abstract 13281: Racial, Gender, or Income Disparities Not Related to Outcomes in the First Year After an Implantable Cardioverter Defibrillator (ICD)
Authors: Dougherty Cynthia M , Reilly Carolyn M , Thompson Elaine A
Published: April 2024

Introduction:
Racial, gender, and income disparities among implantable cardioverter defibrillator (ICD) recipients have been widely reported. In particular, African Americans (AA), women, and those with lower socioeconomic status (SES) are less likely to receive an ICD or report poorer outcomes after ICD implant. The
purpose
of this study was to determine if racial, gender, or income disparities had an impact on number of ICD shocks or all cause hospitalization in the first year after initial ICD implant.

Methods:
300 patients receiving an initial ICD in the Pacific NW were followed for 1 year. Patients were (mean±SD) 64±12 years old, 90% Caucasian, 4% AA, 2% Am Indian (AI), 2% Latino, 75% male, 87% living in urban areas, with 25% employed FT, 10% PT, and 43% retired, averaging $30-49K in household income. ICD shocks and hospitalizations were verified using medical records. Descriptive statistics, Chi
2
, and correlations were used to examine for health disparities in clinical outcomes over 1 year.

Results:
There were no significant associations between race, gender or SES and outcomes of ICD shock or all cause hospitalization within 1 year. For
race
, 10.7% of Caucasians and 0.7% of all other races received an ICD shock (X
2
=3.36, p=0.50); 28% of Caucasians, 2.7% of AA, 1.4% AI, and 0.7% Latino were hospitalized (X
2
=1.57, p=0.81). For
gender
, 3.4% of women and 9.5% of men received an ICD shock (X
2
=0.20, p=0.65); 4.7% of women and 29.1% of men were hospitalized (X
2
=3.0, p=0.08). For
SES
, 5.6% in $10-29K, 3.5% in $30-49K, and 2.1% in >$90K received an ICD shock (X
2
=10.3, p=0.07); 6.9% in $10-29K, 11.8% in $30-49K, and 5.6% in >$90K were hospitalized (X
2
=6.4, p=0.27). Results showed trends (p<.10) of men more likely to be hospitalized and those with lower SES more likely to have ICD shocks in the first year.

Conclusions:
We found no statistically significant associations between patient race, gender or income and the incidence of ICD shocks or hospitalizations in the first year post-ICD implant. Other research reveals disparities with respect to who receives an ICD, but these findings reveal no differences in ICD-related outcomes once patients have received an ICD.
Abstract 13424: Prospective Trial of Adenosine on Atrioventricular Nodal Conduction in the Pediatric Transplanted Heart
Authors: Flyer Jonathan N , Zuckerman Warren A , Richmond Marc E , Anderson Brett R , Mendelsberg Tamar G , McAllister Jennie M , Liberman Leonardo , Addonizio Linda J , Silver Eric S
Published: April 2024

Introduction:
Supraventricular tachycardia (SVT) is common after heart transplant. Adenosine is the standard of care for SVT treatment in children and adults, but is relatively contraindicated post-transplant due to presumed risk of prolonged atrioventricular (AV) block in denervated hearts. This is the first trial of adenosine use in pediatric and young adult heart transplant patients.

Hypothesis:
Adenosine use after heart transplant does not cause prolonged asystole and is effective in blocking AV nodal conduction.

Methods:
This was a single center prospective clinical trial including healthy heart transplant recipients ages 6 months - 25 years presenting for routine cardiac catheterization from July 2015 to April 2016. After catheterization, a pacing catheter was placed in the right ventricle and adenosine was given according to a stepwise protocol (12.5mcg/kg, 25mcg/kg, 50mcg/kg, 100mcg/kg and 200mcg/kg, with maximum doses of 0.8mg, 1.5mg, 3mg, 6mg and 12mg for patients ≥ 60kg) until AV block was achieved. The primary outcome was clinically significant asystole ≥ 12 seconds following adenosine that required rescue ventricular pacing. The effects of patient characteristics on adenosine dose and total adenosine effect were tested.

Results:
Eighty patients completed adenosine testing. No patient (0%, 95% CI 0-3%) required rescue ventricular pacing. AV block was observed in 77 patients (96%, 95% CI 89-99%) at different doses (Figure 1). The median longest AV block was 1.9 seconds (IQR 1.4-3.2) and the mean total adenosine effect was 4.3 seconds (±2.0). No patient characteristics were significant predictors of adenosine dose and total adenosine effect. Results were similar when patients were stratified by weight ≥60kg.

Conclusion:
Adenosine is a safe medical therapy for the induction of AV block in pediatric and young adult heart transplant patients when using low initial doses (25mcg/kg; 1.5mg if ≥60kg) and gradually escalating therapy.
Abstract 13431: Safety And Efficacy of Angioseal Deployment in Patients With Common Femoral Artery Access During Electrophysiological Procedures Performed With Uninterrupted Oral Anticoagulation
Authors: Gianni Carola , Engel Jason T , Powers Brent M , Mohanty Sanghamitra , Trivedi Chintan , Bai Rong , Al-Ahmad Amin , Burkhardt J D , Gallinghouse G J , Hranitzky Patrick M , Horton Rodney P , Sanchez Javier E , Beheiry Salwa , Di Biase Luigi , Natale Andrea
Published: April 2024

Introduction:
Retrograde access is commonly used during EP procedures to access the aortic root as well as the LV. Many patients who undergo these procedures are under uninterrupted oral anticoagulation (OAC), therefore it is important to find a way to minimize arterial access-site complications.

Hypothesis:
Femoral arterial access closure devices can be safely used to achieve hemostasis after common femoral artery access in EP procedures performed with uninterrupted OAC.

Methods:
Consecutive patients who underwent femoral arterial access closure with the AngioSeal device in two centers were included in this retrospective analysis. All patients were systemically heparinized with ACT between 300 and 500 s. Success was defined as hemostasis achieved in < 5 minutes.

Results:
Over a 2-year period, 62 patients underwent femoral arterial access closure. 52% were PVC/VT ablations, 40% AF (NCC), and 8% SVT (NCC/WPW). 53% of the patients were female, with a mean age of 59 ± 13 years and BMI 30.0 ± 5.2; sheath size was 8F for all.

40% on uninterrupted OAC (24% factor Xa inhibitors, 16% warfarin), whereas 23% were on ASA, 5% on dual antiplatelet therapy, and 32% were not receiving any antithrombotic therapy at the time of the procedure. In all patients with uninterrupted OAC, femoral arterial access was ultrasound-guided to ensure that the arteriotomy was located above the bifurcation but below the external iliac artery.

Femoral arterial closure was successful in all, without any device-related complication. There were 2 (3%) access-related complications requiring prolonged hospitalization, both related to the additional venous access, as determined by ultrasound: 1 superficial bleeding in a patient with NCC tachycardia during AF ablation who was on uninterrupted rivaroxaban and 1 large hematoma in a patient who underwent VT ablation and was on ASA. The incidence of complications was not significantly different between patients with uninterrupted OAC compared to those with uninterrupted antiplatelet thereapy or no antithrombotic therapy (Fischer’s exact test P = NS).

Conclusions:
Common femoral artery access closure with the AngioSeal device is safe and effective in achieving hemostasis in patients undergoing EP procedures performed with uninterrupted OAC.
Abstract 13434: Relationship Between Fluoroscopy Time, Absorbed Dose And Effective Dose In A High-volume Electrophysiology Laboratory
Authors: Gianni Carola , Engel Jason T , Mohanty Sanghamitra , Trivedi Chintan , Bai Rong , Al-Ahmad Amin , Burkhardt J D , Gallinghouse G J , Hranitzky Patrick M , Horton Rodney P , Sanchez Javier E , Di Biase Luigi , Natale Andrea
Published: April 2024

Introduction:
It is important to correctly quantify radiation exposure to assess the deterministic (tissue damage) and stochastic (cancer and genetic changes) risk associated with fluoroscopy use.

Hypothesis:
There is little correlation between fluoroscopy time and both the absorbed dose (AD; deterministic risk) and the effective dose (ED; stochastic risk) measured during EP procedures.

Methods:
A retrospective analysis of radiation dose data for subjects undergoing EP procedures in which fluoroscopy was used. Data collected included fluoroscopy time (min), dose area product (DAP - Gy*cm
2
) and AD or air kerma (AK - mGy). The ED was calculated by multiplying DAP with a conversion factor of 0.20 mSv/(Gy*cm
2
).

Results:
3331 consecutive EP procedures were analyzed. Overall, the correlation between DAP/ED and AD is strong (r = 0.63, P < .000001), while between fluoroscopy time and AD is moderate (r = 0.46, P < .000001), and between fluoroscopy time and DAP/ED is weak (r = 0.26, P < .000001).

There were wide variations in dose and statistically significant differences in fluoroscopy time, DAP/ED, and AD depending on the nature of the procedure, with AF ablation conferring the highest values, followed by BIV implant, LAA exclusion and VT ablation procedures (Table). When considering AF ablation procedures, radiation exposure was found to be highly operator dependent (Figure).

Conclusions:
Fluoroscopy time does not correlate well with both ED and AD. Therefore, it shouldn’t be the sole indicator of radiation exposure reported for EP procedures, as it does not accurately reflect neither the stochastic nor the deterministic risk.
Abstract 13460: Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin for Adverse Events in Patients With Acute Decompensated Heart Failure
Authors: Nakada Yasuki , Kawakami Rika , Ueda Tomoya , Nakano Tomoya , Kawata Hiroyuki , Okura Hiroyuki , Saito Yoshihiko
Published: April 2024

Background:
urinary neutrophil gelatinase-associated lipocalin (U-NGAL) has been reported as an earlier predictor of acute kidney injury (AKI) and a prognostic factor of adverse events in patients with chronic heart failure, but in acute decompensated heart failure (ADHF) patients the significance is poorly understood.

Methods:
We have studied consecutive 436 patients with ADHF admitted to our department from 2011 through 2014. Among these patients, 260 patients measured U-NGAL using 24-hour urine samples collected on day 1 were studied. The primary endpoints were all-cause death, cardiovascular (CV) death and HF admission.

Results:
We divided into two groups on the basis of the median U-NGAL levels (32.5 μg/gCr). The high U-NGAL group had significantly higher the occurrence of AKI during hospitalization than the low U-NGAL group (p=0.0012). Kaplan-Meier analysis revealed that high U-NAGL group had worse prognosis than low U-NGAL group in all-cause death (Hazard ratio (HR): 2.07; 95% confidence interval (CI): 1.38-3.12, p=0.0004), CV death (HR: 2.29; 95% CI: 1.28-4.24, p=0.0052), and HF admission (HR: 1.77; 95% CI: 1.13-2.77, p=0.0119) (Figure 1). Multivariate analysis revealed that high U-NGAL predicted all-cause death and HF admission (HR: 1.77; 95% CI: 1.17-2.72, p=0.0073; and HR: 1.69; 95% CI: 1.05-2.72, p=0.0293, respectively). In subgroup analyses, high U-NGAL predicted all-cause death in reduced LVEF (HFrEF, <50%) patients, but not in preserved LVEF (HFpEF, ≥50%) patients, with the significant interaction (p=0.0005) (Figure 2).

Conclusions:
In ADHF patients, elevated level of U-NGAL was related to development of clinical AKI and associated with poor prognosis.
Abstract 13473: Increased Blood Residence Time on Transcatheter Aortic Valve Leaflets as a Precursor Mechanism to Leaflet Thrombosis following Valve-in-Valve Procedure: A Patient-Specific Simulation Study
Authors: Vahidkhah Koohyar , Javani Shahnaz , Abbasi Mostafa , Azadani Peyman N , Tandar Anwar , Azadani Ali N
Published: April 2024

Introduction:
Leaflet thrombosis following valve-in-valve (ViV) procedures has been increasingly recognized. Nevertheless, the underlying mechanisms are not well-addressed and remained unclear.

Hypothesis:
Unlike surgical bioprostheses, the aortic portion of the transcatheter aortic valve (TAV) frame is circumferentially surrounded by degenerated bioprostheses in ViV (Fig 1 a-b). The geometric confinement of the TAV leaflets increases the blood residence time (BRT) on the leaflets. This acts as a precursor mechanism to the thrombus formation.

Methods:
A patient-specific geometry of the left ventricle, aorta, and coronary arteries was reconstructed from computed tomographic angiography (CTA) images using Simpleware software (Fig 1c). Two computational models representing a surgical bioprosthesis and a TAV in ViV setting were developed in the patient-specific geometry. 3D flow fields were obtained via a one-way fluid-solid interaction modeling approach. Thereafter, a particle tracking procedure was applied to calculate BRT on the leaflets. Finally, statistical analysis was performed to compare the BRT values between the two models.

Results:
Tracking of the blood particles in close proximity of the leaflets demonstrated significantly longer BRT on the aortic side of the leaflets in the ViV setting than surgical bioprosthesis (Fig 1d). During systole and diastole, the amount by which the mean BRT was higher for ViV than surgical valve was 341% and 90%, respectively (p<0.001).

Conclusions:
The results of this study show that geometric confinement of TAV in ViV disrupts flow between the leaflets and the aortic sinuses, and increases the likelihood of thrombogenesis.
Abstract 13490: Cardiac Progenitor Cell Therapy in Right Heart Failure With Preserved Ejection Fraction
Authors: Ousaka Daiki , Goto Takuya , Ishigami Shuta , Sano Toshikazu , Hirai Kenta , Ohtsuki Shinichi , Kasahara Shingo , Sano Shunji , Oh Hidemasa
Published: April 2024

Background:
Hear failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by normal EF with abnormal relaxation. Although the significance of HFpEF in right ventricle (RV) remains elusive as well as cell therapy responses in HFpEF patients with single ventricular heart diseases (SHD) have not yet clarified.

Purpose:
We investigated the underlying mechanisms and potential benefits of cardiosphere-derived cell (CDC) therapy in HFpEF includes rat models and human SHD.

Methods:
Pulmonary artery banding (PAB) was created in rats for 4 weeks as RV failure models. In human study, 40 patients, aged 2.2±1.4 years, 91% diagnosed as RV type SHD, were analyzed. Both rat and human studies were defined as follows (HFpEF; EF≧40%, HFrEF; EF<40%), and intracoronary CDC infusion responses were assessed.

Results:
Rats received PAB showed RV dysfunction with significant cardiac fibrosis those were addressed by increased expression of heart failure or fibrosis related genes in both HFpEF and HFrEF rats rather than controls. CDC infusion led to marked increase in EF in rats with HFrEF but not HFpEF. Although CDC infusion did not augment EF in HFpEF, this treatment significantly decreased interstitial fibrosis and improved myocardial elastance in both HFpEF and HFrEF compared with baseline. Furthermore, CDC treatment markedly reduced Col1, Col3, NPPA and MMP2 expressions in both groups, whereas inflammatory cytokine such as Ccl2 and IL6 decreased only in HFrEF. Notably, CDC infusion did not affect the expression of MMP9, TIMP1 and TIMP2 in both groups. In human study, there was no difference in the incidence of late gadolinium enhancement detected by cMRI in two groups (20% in HFrEF and 15% in HFpEF); however, HFrEF but not HFpEF patients demonstrated a marked improvement in EF and reduced ventricular volumes and mass one year after CDC infusion. In contrast, the beneficial effects of CDC therapy could be observed by improved myocardial strain, elastance, and diastolic function in both groups.

Conclusions:
Our translational and clinical research of HFpEF in RV suggests that CDC infusion may have significant impact on diastolic relaxation and myocardial stiffening improvements to reverse ventricular fibrosis and remodeling leading to RV failure.
Abstract 13503: Efficacy of Subcutaneous Implantable Cardioverter Defibrillator Defibrillation Testing in Hypertrophic Cardiomyopathy Patients at High Risk of Sudden Cardiac Death
Authors: Maurizi Niccolo’ , Tanini Ilaria , Olivotto Iacopo , Amendola Ernesto , Limongelli Giuseppe , Rapacciuolo Antonio , Esposito Francesca , Viani Stefano , Allocca Giuseppe , Sitta Nadir , Perego Giovanni Battista , Ricciardi Giuseppe , Pieragnoli Paolo , De Filippo Paolo , Ferrari Paola , Quarta Giovanni , Bongiorni Maria Grazia , Cecchi Franco
Published: April 2024

Introduction:
Subcutaneous ICD (S-ICD) is a promising option for Hypertrophic Cardiomyopathy (HCM) patients at high-risk of Sudden Cardiac Death (SCD). However, its efficacy in terminating ventricular arrhythmias in HCM is yet unresolved.

Hypothesis:
To determine the efficacy of post-implantation S-ICD defibrillation testing (DT) of Ventricular Fibrillation (VF) in HCM patients and assess possible predictors of failure.

Methods:
Consecutive HCM patients referred for S-ICD implantation at seven Italian Centers from June 2014 to May 2016 were prospectively enrolled. At S-ICD implantation, patients underwent one or two attempts of VF induction by programmed electrical stimulation. Successful conversion was defined as any 65j shock that terminated VF and did not require rescue shocks. Clinical, ECG and Echocardiographic findings were analyzed to study potential predictors of conversion failure.

Results:
We evaluated 50 HCM patients (34 males, mean age 40±16) with a mean BMI of 25.2±4.4 kg/m
2
[18.1-36]. Two patients (4%) had a history of cardiac arrest, whereas 48 (96%) were implanted in primary prevention. Mean calculated risk of SCD at 5 years by the ESC score was 6.5±3.9% and all patients had at least one major risk factor. Maximal LV wall thickness (LVMWT) was >25 mm in 19 (38%) patients and ≥ 30 mm in 13 (26 %). In 2/50 patients (4%) no arrhythmias were inducible, while in 7 (14%) only polymorphic sustained ventricular tachycardia (SVT) was induced and correctly cardioverted by the S-ICD. In the remaining 41 (82%) patients, 70 VF episodes were induced (2 VF in 29 and 1 VF in 12 patients), all correctly recognized by the device. Of the 70 VFs, 4 (6%) spontaneously converted into sinus rhythm. In 65/66 (98%) the S-ICD performed successful conversions, but failed in 1 (2%) patient, who needed rescue defibrillation. This patient was severely obese, with a BMI 36 kg/m
2
and LVMWT of 25 mm. VF was induced again and successfully converted by 80j shock with inverted polarity.

Conclusions:
Acute defibrillation testing at 65j shows the efficacy of S-ICD in terminating VF or polymorphic SVT in HCM patients, despite the presence of extreme LV hypertrophy. Severe obesity was possibly responsible for the single failure observed at 65j in our series.
Abstract 13514: Serial Quantitative Assessment of Thrombogenicity in LVAD Recipients: A Case for Personalized Antithrombotic Therapy
Authors: Shah Palak , Bliden Kevin , Tantry Udaya , Phillips Sheila , McLeod Christopher , Singh Ramesh , Connor Christopher O , Gurbel Paul
Published: April 2024

Introduction:
Bleeding and thrombotic complication affect between 25-40% of left ventricular assist device (LVAD) recipients. Measures of thrombogenicity such as maximum platelet-fibrin clot strength (MAKH), endogenous thrombin potential (ETP) and platelet reactivity may indicate thrombotic and bleeding risk in patients on LVAD support and may vary after LVAD implantation.

Methods:
We prospectively assessed thrombogenicity using the novel point-of-care (TEG-6S) with PlateletMapping and the calibrated automated thrombogram (CAT) in 31 patients before and serially after LVAD implantation (HeartWare HVAD, n = 17; Heartmate II, n = 14). All LVAD patients were on aspirin 325mg/daily and warfarin (INR 2.0 to 2.5) therapy. Standard hematologic and hemolysis laboratories were compared.

Results:
Markers of thrombogenicity were highly variable post-LVAD. Overall, in the acute phase, MAKH, and maximum ADP-, and arachidonic acid (AA)-induced clot strength increased (p < 0.05, Table) and returned to near baseline by ≥3 months. Despite target INR values at ≥ 3 months (2.0±0.3) and antiplatelet therapy, the R-time (7.1±1.8min) remained within the normal range. Hypercoagulable patients (MAKH≥69mm) had higher endogenous thrombin potential, peak thrombin generation, WBC count, and LDH (p≤0.05).

Conclusions:
A state of heightened thrombogenicity indicated by high MAKH and high platelet reactivity are present in the acute phase after LVAD implantation and in selected patient during the chronic phase despite therapy with warfarin/aspirin. These findings suggest that intensification of antithrombotic therapy in a personalized fashion based on sensitive thrombogenicity testing, rather than INR should be investigated to mitigate adverse events.
Abstract 13520: Empagliflozin Reduces Markers of Arterial Stiffness, Vascular Resistance and Cardiac Workload in EMPA-REG OUTCOME
Authors: Chilton Robert J , Gullestad Lars , Fitchett David , Inzucchi Silvio E , Mattheus Michaela , Woerle Hans Juergen , Johansen Odd Erik
Published: April 2024

Introduction:
In EMPA-REG OUTCOME
®
, empagliflozin added to standard of care in patients with type 2 diabetes and established vascular disease, significantly reduced the primary composite outcome of CV death, non-fatal myocardial infarction or non-fatal stroke, a result driven mainly by a 38% reduction in CV death. We aimed to assess the vascular effects of empagliflozin in the trial, beyond its recognized effects in reducing systolic blood pressure (SBP) and diastolic BP (DBP).

Hypothesis:
We hypothesized that empagliflozin reduced 1) pulse pressure (PP), a vascular marker of arterial stiffness determined by the cardiac output, the stiffness of elastic central arteries and wave reflection (PP = SBP - DBP), 2) mean arterial pressure (MAP), a measure reflecting the cardiac cycle determined by the cardiac output, systemic vascular resistance, and central venous pressure (MAP = ([2 x diastolic BP]+ systolic BP)/3), and 3) the double product (DP), a marker of cardiac workload and an indirect measure of myocardial oxygen demand (DP = heart rate x SBP).

Methods:
Patients with type 2 diabetes and high CV risk were randomised to receive placebo, empagliflozin 10 mg, or empagliflozin 25 mg in addition to standard of care. We analysed changes from baseline to week 164 for SBP, DBP, HR, PP, MAP and DP, between treatment and placebo groups using a mixed model repeated measures analysis.

Results:
In total, 2333, 2345 and 2342 patients received placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively and followed for a median period of 3.1 years. There were nominal significantly greater reductions in PP, MAP and DP with empagliflozin treatment as compared with placebo (Table), without increases in mean HR (Table).

Conclusions:
Empagliflozin had favorable effects on BP, arterial stiffness, vascular resistance and on the indirect measure of cardiac workload. Further analyses are needed to determine the potential contribution of these changes to the reduction in CV mortality.
Abstract 13530: New Insights Into CPR Optimization Through a Flow per Compression Analysis of Chest Compression Generated Blood Flow
Authors: Lampe Joshua W , Yin Tai , Bratinov George , Shoap Wes , Lin Yuxi , Kaufman Christopher L , Becker Lance B
Published: April 2024

Introduction:
During cardiac arrest and CPR, the two primary pumps of the cardiovascular circuit (the right and left ventricles) are supplanted by a single pump, the chest compression. In pre-clinical experiments, blood flows are reported as the amount of flow per minute (L/min). Characterizing flow on a per minute basis is highly dependent on chest compression (CC) rate. Analysis of flow generated by each compression (“cardiac output” in L/comp) could reveal important information relevant to lung perfusion and how the circuit as a whole is responding to CPR.

Hypothesis:
It was hypothesized that increasing CC rate would improve per minute blood flow but reduce flow on a per compression basis.

Methods:
CPR was performed on nine domestic swine (~30 kg) using standard monitoring. Flow was measured in the right common carotid and abdominal aorta. Ventricular fibrillation was electrically induced. Mechanical CC were started after ten minutes of untreated VF. CC were delivered at rates of 50, 75, 100, 125, or 150 compressions per minute (cpm) and a depth of 2” for a total of 54 min. CC rates were changed every 2 min and were randomized.

Results:
Mean blood flows are shown in L/min (solid line) and L/comp (dashed line) in Figure 1 for minutes 0-10 and 10-20. Across all rates, per minute flows were strongly rate dependent in minutes 0-10, favoring fast rates, and were weakly rate dependent in minutes 10-20, favoring rates near 100 CPM. Across all rates, per compression flow had a weaker rate dependence in minutes 0-10, favoring rates less than 100 CPM, but during minutes 10-20 had a strong rate dependence, also favoring rates less than 100 CPM.

Conclusions:
While CC rates greater than 100 cpm may provide more total blood flow early during CPR, analysis of blood flow per compression indicates that they can become detrimental after 10 minutes of ongoing CPR. During a prolonged resuscitation, a longer time after a given compression might be needed for venous refill thereby favoring rates of 100 cpm or less.
Abstract 13826: Atrial Fibrillation Symptom Clusters Increase Hospitalizations and Emergency Department Visits
Authors: Streur Megan , Ratcliffe Sarah , Shoemaker M. Benjamin , Riegel Barbara
Published: April 2024

Introduction:
Symptoms are a predictor of hospitalizations in adults with atrial fibrillation (AF). Symptom clusters are groups of two or more symptoms that are related due to shared mechanisms or a shared impact on outcomes. The impact of AF specific symptom clusters on hospitalization and emergency department (ED) visits has not previously been examined.

Hypothesis:
We assessed the hypothesis that symptom clusters were associated with AF-related hospitalizations and ED visits.

Methods:
We examined pre-existing data for 1,501 adults in the Vanderbilt AF Registry, a clinical biorepository that prospectively enrolls both AF patients and their family members. Our sample consists of subjects with confirmed AF and a completed symptom survey (derived from the University of Toronto AF Severity Scale, Chronbach’s α for symptom burden is 0.94). Seven common AF symptoms were measured on a 5 point Likert scale. Our outcomes were self-reported number of AF-related hospitalizations and ED visits in the past 12 months. To identify symptom clusters we used hierarchical cluster analysis, Ward’s method, and Euclidean distance as the dissimilarity measure. The ideal number of clusters was determined with dendrograms, pseudo F, and pseudo T. We used Poisson regression to examine whether the identified clusters were associated with hospitalization and ED visit rates controlling for clinical characteristics.

Results:
Our sample was primarily male (67%) and Caucasian (96%) with a mean age of 58.4 (± 12.2) years. Two symptom clusters were identified, which we labeled the
At Rest
cluster (fatigue at rest, shortness of breath at rest, chest pain, and dizziness) and the
With Activity
cluster (shortness of breath with activity and exercise intolerance). Palpitations was the only symptom that did not cluster with other symptoms. Subjects who experienced all the symptoms in the At Rest cluster had an adjusted incident rate ratio for hospitalizations of 1.9 (p<0.0001) and for ED visits of 2.8 (p<0.0001). There was no statistically significant association between the With Activity cluster and either clinical outcome.

Conclusion:
We identified two AF-specific symptom clusters. Only the At Rest cluster was significantly associated with AF-related hospitalizations and ED visits.