bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16878: Exercise Intolerance in Heart Failure With Preserved Ejection Fraction is More Closely Related to Energetic Decline During Exercise Than to Mitochondrial Oxidative Capacity in Recovery
Authors: Samuel T. Jake , Lewsey Sabra , Schaer Michael , Weiss Kilian , Steinberg Angela M , Sourdon Joevin , Bottomley Paul A , Gerstenblith Gary , Weiss Robert G
Published: December 2023

Introduction:
Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with severe exercise intolerance (EI) and exertional fatigue. Impaired skeletal muscle high-energy phosphate metabolism has been reported in HFpEF patients and postulated as a potential contributor to EI. However, whether EI is more closely related to rapid energetic decline during exercise, or reduced mitochondrial oxidative capacity remains unknown.

Hypothesis:
We hypothesized that six-minute walk distance (6MWD) is more closely related to the rate of skeletal muscle energetic decline during exercise than mitochondrial oxidative capacity in HFpEF.

Methods:
Calf muscle energetics were measured by phosphorus magnetic resonance spectroscopy (
31
PMRS). The rate of phosphocreatine (PCr) decline normalized to work performed during graded plantar flexion exercise to volitional fatigue and the time for PCr post-exercise recovery, an established metric inversely related to mitochondrial oxidative capacity, were measured in 64 HFpEF patients (age: 65 ± 11 years; 53% women).

Results:
The mean rate of PCr decline, PCr recovery time, and 6MWD were 52 ± 108 μmol/g wet weight/KJ, 80 ± 45 seconds, and 296 ± 109 meters, respectively. The 6MWD was inversely related to the rate of PCr decline (r = -0.46; P = 0.0002;
Figure, A
) but not significantly related to the PCr recovery time (r = -0.06; P = 0.66;
Figure, B
), as determined by Pearson’s correlation coefficients.

Conclusions:
EI, as measured by 6MWD, in HFpEF patients is closely associated with impaired skeletal muscle metabolism, specifically rapid skeletal muscle PCr decline during exercise rather than mitochondrial oxidative capacity. This suggests that impaired glycolytic metabolism and substrate delivery may contribute metabolically to EI in HFpEF patients.
Abstract 16885: Progression of Aortic Valve Stenosis in Atrial Fibrillation versus Sinus Rhythm: Implications for Clinical Practice and Severe Aortic Stenosis Diagnosis
Authors: Fabre Katarina L , Nkomo Vuyisile T , Ito Saki , Lewis Bradley R , Pislaru Sorin V , Miranda William R , Oh Jae K
Published: December 2023

Introduction:
Rate of aortic stenosis (AS) progression in patients with concurrent atrial fibrillation (AF) has not been previously described. Objectives: To describe changes over time in aortic valve area (AVA) and associated hemodynamics during AS progression in patients in AF versus sinus rhythm (SR).

Methods:
Patients with AVA ≤ 1 cm
2
and preserved left ventricular ejection fraction ≥50% were identified from the Mayo Clinic Echocardiographic Laboratory Database. Serial echocardiograms prior to the development of AVA ≤ 1 cm
2
(Time 0) were examined. Inverse probability weighting was used for statistical analysis.

Results:
A total of 166 patients were included (SR=79 and AF=87), mean age 78.1 ± 7.8 years, females 31%. The rates of AVA reduction (-0.14±0.01 vs -0.12±0.01 cm2/year, p=0.31) and increase in trans-aortic peak velocity (+0.23 ± 0.02 vs +0.22 ± 0.02 m/sec, p=0.55) and mean gradient (MG) (3.9 ± 0.3 vs 3.8 ± 0.4 mmHg, p=0.83) did not differ between AF and SR (Figure 1). However, AF was associated with systematically lower forward stroke volume index (SVi), peak velocity and MG for the same AVA compared to SR (p<0.04 for all) throughout AS progression. When AVA reached 1 cm
2
, SVi (38.8±6.6 vs 45.7 ±8.9, p=0.02), peak velocity (3.9 ± 0.6 vs 4.1 ± 0.6 m/sec, p=0.04) and MG (36.6±10.9 vs 41±12.8 mmHg, p=0.03) were lower in AF compared to SR.

Conclusions:
The rate of AS progression was not different in AF versus SR. However, forward flow was systematically lower in AF resulting in discordant AS during AS progression and when AVA reached 1 cm
2
. Doppler velocity and MG criteria for severe AS appear to be lower in AF versus SR which has implications for timely diagnosis of severe AS and patient management.
Abstract 16890: Postoperative Atrial Fibrillation Following Coronary Artery Bypass Surgery in Severe Obesity: Impact of Waist Circumference
Authors: Roberge Jeanne , Paquin Amelie , Oconnor Sarah , Poirier Paul , Voisine Pierre , Piche Marie Eve E
Published: December 2023

Introduction:
Obesity (body mass index (BMI) ≥ 30 kg/m
2
) is an independent risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) surgery. The incidence of POAF in patients with severe obesity (BMI ≥ 35 kg/m
2
) is less studied. For a given BMI, higher waist circumference (WC) predicts adverse cardiovascular outcomes. Whether WC predicts POAF independently of BMI among patients with severe obesity remains unknown.

Aim:
To evaluate the risk of POAF after isolated CABG in patients with severe obesity, and the role of WC in predicting POAF in this population.

Methods:
Our cohort included 7,995 patients undergoing isolated CABG (2006-19). Patients with atrial fibrillation were excluded. POAF risk was compared across BMI and WC categories. In patients with severe obesity, the association of a 10 cm incremental in WC with POAF risk was assessed. We used a log-binomial regression model. Results are presented as adjusted relative risks (aRR) with 95% confidence intervals (CI).

Results:
763 (9.5%) patients had a BMI ≥ 35 kg/m
2
. Mean BMI was 38.5 ± 3.6 kg/m
2
and WC was 123.4 ± 10.8 cm. The severe obesity group was younger (63 ± 9 vs. 67 ± 9 years,
p
<0.01) and had a higher proportion of females (28 vs. 21%,
p
<0.01) compared to normal BMI. More patients with severe obesity developed POAF (37 vs. 29%, aRR: 1.52 [95%CI 1.36-1.72],
p
<0.01). aRRs of POAF according to BMI and WC categories are presented in Table 1. Independently of BMI, every 10 cm increment in WC among patients with severe obesity was associated with an increased risk of POAF (aRR: 1.17 [95%CI 1.09-1.25],
p
<0.01).

Conclusions:
POAF after CABG is prevalent in patients with severe obesity. Our results showed a gradient of increasing POAF risk with increasing BMI and WC. In patients with severe obesity, WC independently provided additional prognostic value beyond BMI. Since POAF is associated with adverse long-term outcomes, WC could be targeted for the development of preventive strategies.
Abstract 169: Effect of Fingolimod-Induced Leucocyte Sequestration on Inflammatory Response and Neurological Damages in a Porcine Model of Cardiac Arrest
Authors: Abi Zeid Daou Yara , Bois Antoine , Watanabe Naoto , Faucher Estelle , Lidouren Fanny , Surenaud Mathieu , Hue Sophie , Kohlhauer Matthias , Ghaleh Bijan , Tissier Renaud
Published: December 2023

Introduction:
Early alterations in immune function are observed after cardiac arrest, with sepsis-like syndrome and cerebral infiltration by leucocytes.

Hypothesis:
The pharmacological sequestration of leucocytes within lymphoid tissues with the sphingosine 1-phosphate analog fingolimod could mitigate the inflammatory response and provide neuroprotection after cardiac arrest.

Methods:
Anesthetized pigs underwent 14 min of ventricular fibrillation followed by resuscitation. Animals randomly received fingolimod (1 mg/kg i.v.) or saline two hours prior to cardiac arrest (n=6 in each group). Blood samples were collected for blood cells count and dosages of cytokines (Luminex) and neurofilament light chain (NFL, Quantmetrix). Neurological dysfunction was assessed 24 hours after cardiac arrest.

Results:
In the Fingolimod group, total blood leucocytes and lymphocytes counts were reduced as compared to Controls, both prior to and after cardiac arrest (Figure 1A). Conversely, blood levels of Interleukin [IL]-R1a, IL-6, IL-8, IL-18 were not different among groups (e.g., Figure 1B for IL-1Ra). As illustrated in Figures 1C and 1D, NFL blood levels and neurological dysfunction score were also not different in both groups after cardiac arrest.

Conclusion:
Despite reducing blood total leucocytes and lymphocytes count, fingolimod did mitigate neither the circulating levels of pro- or anti-inflammatory cytokines nor the neurological damage following cardiac arrest. Leucocytes sequestration in lymphocyte tissue might not be sufficient to provide neuroprotection after cardiac arrest.

Figure 1: Blood lymphocytes (A), Interleukin-1Ra blood level (B), Neurofilament light chain blood level (NFL; C) and Neurological Dysfunction score at Day 1 after cardiac arrest
Abstract 16964: Predictive Value of Blood Cellular Indices for 30-day Mortality in Patients With Acute Pulmonary Embolism. Data From the RIETE Registry
Authors: Siddiqui Fakiha , Tafur Alfonso J , Garcia-Ortega Alberto , Kantarcioglu Bulent ,   RIETE Registry, Fareed Jawed , Monreal Manuel
Published: December 2023

Introduction:

In patients with acute pulmonary embolism (PE), the prognostic value of cellular indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), or systemic immune-inflammation index (SII, NLR*platelets) is uncertain. The aim of this study is to investigate the relationship between blood cellular indices (NLR, PLR and SII) and adverse outcome as 30-day mortality in a cohort of patients recruited in the RIETE registry.

Methods:
In this study, the data of 10085 patients from the RIETE registry were used to estimate the association between NLR, PLR or SII with the 30-day mortality in patients with acute PE. They were randomly separated into a derivation cohort (n=6,710) and validation cohort (n=3,375). Results of the logistic regression analyses in the derivation cohort were then validated using the validation cohort.

Results:
In the derivation cohort, median values of NLR were: 4.3 (IQR: 2.7-7.3), PLR 151 (IQR: 104-231), and SII: 958 (IQR: 568-1,739). During the first 30 days, 315 (4.7%) patients died, 32 (0.5%) developed VTE recurrences and 142 (2.1%) major bleeding. On multivariable analyses, patients who subsequently died more likely had NLR >5.0 (OR: 3.08; 95%CI: 2.26-4.20), PLR >160 (OR: 2.40; 95%CI. 1.75-3.29) or SII >1,000 (OR: 2.14; 95%CI: 1.60-2.86). The results were further endorsed by the validation cohort where NLR >5.0 (OR: 2.42; 95%CI: 1.57-3.74), PLR >160 (OR: 1.87; 95%CI. 1.25-2.82) or SII >1,000 (OR: 2.10; 95%CI: 1.34-3.29) predicts 30-day mortality.

Conclusions:
These studies suggest that patients with elevated NLR >5, PLR >160, and SII >1000 values at baseline were determined to be at increased risk for death in 30-days.
Abstract 16968: Hypoxia-Lactate Dehydrogenase A-Lactate Axis Mediated Metabolic Adaptation of Macrophage Promotes Vascular Remodeling of Pulmonary Hypertension
Authors: Wang Na , Li Qiang , Wang Feilong , Ji Yingqun
Published: December 2023

Introduction:
Early recruitment of inflammatory macrophages with subsequent adaptation into pro-fibrotic phenotype have been reported essential for the development of PH. However, the underlying mechanism remains undetermined.

Hypothesis:
With enhanced glycolysis under hypoxic conditions, lactate dehydrogenase A(LDHA) mediated accumulation of lactate facilitates metabolic adaptation of macrophages and promotes the development of PH.

Methods:
Circulating monocytes, lactate, LDHA expression level were analyzed from patients with PH. The expression of LDHA, iNOS, and Arg1 in macrophages within lung tissue were examined on histopathology from patients with IPAH. Mice with myeloid specific knockout of
Ldha
were generated, and hemodynamic measurement, echocardiogram, histopathological examinations were conducted to evaluate pulmonary vascular remodeling using Su/Hx PH model. Bone marrow derived macrophage (BMDM) and vascular smooth muscle cells (SMCs) from mice were harvested for the mechanism study.

Results:
Lactate, monocytes and LDHA expression in PBMC were elevated in PH patients. On histopathology, perivascular macrophages infiltration with overexpression of LDHA, iNOS and Arg1 was noticed from lung tissue of IPAH patients, similar seen in both MCT-PH rats and Su/Hx mice. Mice with myeloid knockout of
Ldha
(
Ldha
lyz2-/-
) shown decreased RVSP and improved right heart function on Echocardiogram. In vitro, inflammatory BMDM shown significantly elevated expression of LDHA and lactate under hypoxia, along with oversecreted growth factors including PDGF-β and promoting SMCs proliferation, which can be reversed by
Ldha
depletion.

Conclusions:
The hypoxia-LDHA-lactate axis plays a crucial role in metabolic adaption of macrophages under hypoxia condition, promoting SMCs proliferation and pulmonary vascular remodeling process. These findings suggest that targeting LDHA-lactate axis might exert therapeutic potential for PH.
Abstract 16969: Assessment of the Electromechanical Window in Patients With Conventional Biventricular Pacing as Compared to Patients With Conduction System Pacing
Authors: Sternick Mykaihla , Spitofsky Nina , Owen Alyson , Pavri Behzad B
Published: December 2023

Introduction:
The Electromechanical Window (EMW) is a validated measurement reflecting electromechanical coupling of the ventricles, and is defined as the difference between electrical and mechanical ventricular activation times. A larger (more negative) EMW is associated with worse clinical outcomes, especially greater arrhythmic risk, in various clinical conditions such as long QT syndrome, risk of drug-inducd torsade, hypertrophic cardiomyopathy, etc. Cardiac resynchronization therapy (CRT) can be achieved by conventional bi-ventricular pacing (BiVP) or conduction system pacing (CSP). We assessed the EMW in patients undergoing CRT via these 2 modalities.

Methods:
Total mechanical activation time was measured from the 5 chamber echocardiographic view as the interval (ms) from the onset of the Q wave to aortic valve closure (mean of 3 measurements). Total electrical activation time (QTcBazett interval, ms) was measured from 12 lead ECGs recorded within 24 hours of the echocardiogram. The EMW was calculated as the difference between the QTc and the mechanical ventricular activation time.

Results:
A total of 60 pts (BiVP=31, CSP=29) were analyzed. There was no significant difference between the heart rates during the ECG and the echocardiogram recorded within 24 hours of each other (74.6 ± 16.5 vs 71.5 ± 12.0 bpm, P=NS). The EMW was significantly more negative in patients with BiVP as compared to CSP (-99.5 ± 70.9 vs -55.2 ± 52.7 ms, P=0.03). When restricting the analysis to patients where the ECG and echocardiographic HRs were within 10 bpm of each other, the difference remained significant (P=0.03).

Conclusions:
Patients in whom CRT is achieved by CSP have less negative EMWs as compared to patients with BiVP. Based on the known association of more negative EMW with increased arrhythmic risk, these data, if confirmed in larger populations with correlation to clinical outcomes, add to the growing evidence to support CSP as the preferred modality for achieving CRT.
Abstract 16971: Unraveling the Burden of Cerebrovascular Disease: Exploring the Role of Peripheral Vascular Disease and Kidney Transplant in End-Stage Renal Disease Hospitalization Rates (Insights From the National Inpatient Sample, 2005 to 2019)
Authors: Canova Tyler J , BAXTER PATRICK , Koizumi Naoru , Ekwenna Obi , Issa Rochell
Published: December 2023

Background:
Patients with end-stage renal disease (ESRD) face a higher risk of cerebrovascular disease, but the impact of peripheral vascular disease (PVD) and a kidney transplant (KiTx) on hospitalization rates for cerebrovascular conditions remains uncertain. This study aimed to investigate the rates of hospitalization for cerebrovascular disease in patients with ESRD, PVD, KiTx, or a combination.

Methods:
Using the National Inpatient Sample (NIS), 2,713,194 ESRD hospitalizations (2005-2019) were analyzed. We focused on two cerebrovascular conditions of interest: 1) cerebral infarction due to thrombosis, embolism, and occlusion (CITO) and 2) artery occlusion resulting in cerebral ischemia (AOSI). Comparative analysis utilized t-tests and odds ratios.

Results:
Among ESRD hospitalizations, 66,927 (2.47%) had KiTx, 63,411 (2.34%) had PVD, and 1,406 (0.05%) had both. Key findings included: 1) ESRD patients with PVD had higher odds of hospitalization for CITO (OR 1.33, CI 1.1-1.8, p=0.009) or AOSI (OR 2.63, CI 2.5-2.8, p<0.001) compared to those without PVD (Fig. 1AB); 2) ESRD patients hospitalized with CITO had higher odds of having KiTx and PVD compared to those without KiTx or PVD (OR 3.17, CI 1.0-9.3, p=0.035, Fig. 1AB); 3) ESRD patients with PVD had higher rates of being hospitalized with AOSI (7.29%) than those without AOSI (2.29%, p<0.001); 4) ESRD patients hospitalized with CITO had higher odds of having KiTx and PVD compared to those without KiTx or PVD (OR 3.17, CI 1.0-9.3, p=0.035, Fig. 1AB) and 5) ESRD patients hospitalized with AOSI demonstrated a higher rate of having KiTx and PVD (0.09%) compared to those without AOSI (0.05%, p=0.002).

Conclusion:
This nationwide analysis reveals that the presence of PVD and KiTx is associated with increased rates of hospitalization for cerebrovascular conditions. These findings underscore the importance of proactive management to mitigate the risk of cerebrovascular disease in this vulnerable patient population.
Abstract 16974: Sudden Cardiac Death With Heart Failure Despite Improvement in LV Ejection Fraction: A Population-Based Study
Authors: Chugh Harpriya , Uy-Evanado Audrey , Sargsyan Arayik S , Aziz Habiba , Jui Jonathan , Nakamura Kotoka , Reinier Kyndaron , Chugh Sumeet S
Published: December 2023

Introduction:
Individuals with heart failure (HF) and severely reduced LVEF (≤35%) have increased risk of SCD and qualify for primary prevention ICD implantation. Guideline-directed medical therapy can improve LVEF in ICD patients but influence on SCD risk remains controversial.

Hypothesis:
In a subgroup of HF patients, improvements in LVEF may not eliminate risk of SCD.Aim: To identify and characterize a subgroup of HF patients who suffer SCD despite improvements in LVEF.

Methods:
From a large, prospective population-based study of SCD in the Northwest US (population ~1 million, 2002-2018), we identified all consecutive patients with an established diagnosis of HF and LVEF≤35%. In the sub-group of patients with at least 2 prior LVEF evaluations (earliest and latest in relation to SCD), individuals with significant improvement in LVEF over time (latest LVEF >35%) were compared to those without improvement in LVEF (latest LVEF ≤35%).

Results:
A total of 1622 individuals suffered SCD with a known diagnosis of HF (65% male, age 72±14) of which 434 had at least 2 LVEF evaluations over time prior to their SCD. Of these 100 (23%) had LVEF ≤35% at their earliest evaluation (mean LVEF 27±6). A subgroup of 46% (n=46) had significant improvement in LVEF between earliest vs latest evaluation (28±6 vs. 49+9, by 20±10, p<0.001) with no improvement observed in the remainder (54%, 25±6 vs. 24±7, by -1±7, p = 0.23). Comparisons of the clinical profile (demographic, coronary disease, comorbidities and medications) did not yield any identifiable differences between the subgroups with and without improvement in LVEF (Table; p>0.05 for all).

Conclusions:
Approximately half of individuals with SCD and a history of HF and LVEF ≤35% had significant improvements in LVEF, but this group could not be distinguished from those without improvements in LVEF by readily available clinical variables. These findings highlight the need for novel markers of SCD risk beyond the LVEF for this subset of HF patients.
Abstract 16980: Real World Performance of a Conduction System Pacing Lead
Authors: Wong Anne J , Kapphahn-Bergs Melanie J , Nadkarni Ishan S , Hauser Robert G , Whelan Jessica R , Casey Susan A , Witt Dawn R , Bank Alan J , Olson Matthew D , Walser-Kuntz Evan T , Sengupta Jay D
Published: December 2023

Introduction:
With the shift towards conduction system pacing (CSP), a technique that preserves ventricular synchrony unlike standard right ventricular pacing (RVP), the use of the smaller diameter fixed-helix Medtronic 3830 4Fr Select Secure lead and its’ special delivery catheter has dramatically increased. The near and long-term performance of the 3830 lead in a large real-world setting remains poorly characterized. Thus, we evaluated our experience with the 3830 lead in comparison to the Medtronic 6Fr stylet-driven active fixation CapSureFix Novus 5076 lead used for conventional RVP.

Hypothesis:
The performance of the 3830 CSP lead is equivalent to that of the 5076 RVP lead.

Methods:
Patients with 3830 CSP or 5076 RVP leads implanted at our institution between January 1st, 2018 and March 1st, 2022 were included. All patients were followed at our institution and lead complications, revisions, explants, and upgrades to present day were tracked. Groups were compared using the chi-squared and Fisher’s exact tests in R 4.2.3.

Results:
The outcomes for 2,077 patients receiving either a 3830 CSP lead (n=1,018) or a 5076 RVP lead (n=1,059) are shown in the table. Initially, 13 (1.3%) 3830 leads could not be implanted vs. 3 (0.3%) 5076 leads (p=0.011). Subsequently, however, total revisions were similar between groups (p=0.20), and there were no significant differences in dislodgement, infection, or need for upgrade. One 3830 lead fractured and was replaced; otherwise, there were no lead failures in either group. The distribution of time from implant to event was also similar (p=.376).

Conclusion:
The long-term performances of the 3830 and 5076 leads are similarly satisfactory. A small proportion of 3830 leads could not be implanted, but overall septal or CSP was reliably achieved with few complications or need for lead revision or upgrade.
Abstract 16988: Conventional and Regionally Distinctive Risk Factors for First-Onset Myocardial Infarction in Bangladesh. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study
Authors: Chowdhury Rajiv , Naheed Aliya , Monower Md Mostafa , Shahzad Sara , Raqib Rubhana , Tasmin Ishrat , Spackman Sarah , Pennells Lisa , Butterworth Adam , Danesh John , Di Angelantonio Emanuele
Published: December 2023

Background:
South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to classic cardiovascular risk factors and distinctive practices more common in South Asian populations.

Hypothesis:
Identifying modifiable risk factors for MI in South Asian populations should inform prevention strategies.

Goal:
To study conventional risk factors and several distinctive South Asian characteristics and practices in relation to the likelihood of first-ever MI in Bangladesh.

Methods:
In a case-control study involving 8,133 first MI cases and 8,122 controls, we calculated odds ratios (ORs) for MI (adjusted, when appropriate, for age, sex, smoking status, history of diabetes, history of hypertension, family history of MI, and LDL-cholesterol) and assessed their potential public health impact using population attributable fractions (PAFs).

Results:
The mean (SD) age of first MI was 53 (11) years. Adjusted ORs (95% CIs) were 2.75 (2.53-2.99) for cigarette smoking, 2.33 (2.08-2.60) for parental history of MI, 2.26 (2.07-2.48) for history of hypertension, 1.79 (1.61-1.98) for history of diabetes, and 1.61 (1.55-1.67) per 1-SD higher LDL-cholesterol. The highest PAFs (95% CIs) were for current cigarette smoking (48.9% [46.1%-51.6%]), higher LDL-cholesterol (32.4% [30.2%-34.4%]) and history of hypertension (14.7% [13.2%-16.1%]). As for regionally distinctive practices, ORs were 4.05 (3.15-5.21) with
biri
smoking, 2.04 (1.48-2.81) with chewing tobacco, and 1.26 (1.05-1.51) with parental history of first cousin marriage.

Conclusion:
In a large case-control study, we confirmed the relevance of several conventional risk factors to risk of first-onset MI in the Bangladesh population. We also identified significant associations with MI of practices distinctive to South Asian populations, including indigenous modes of tobacco consumption and parental first-cousin marriage, apparently independent of conventional risk factors. These findings should help identify opportunities for cardiovascular disease prevention in South Asia that embrace both conventional and regionally distinctive risk factors.
Abstract 16997: Cardiomyocyte-Autonomous and Microtubule Dependent Mechanisms Are Sufficient to Mediate Load-Dependent T-Tubule Remodeling
Authors: Courelli Vasiliki , Petrosino Jenn , Uchida Keita , Cheng Lan , Song Leo , Vite Alexia , Prosser Benjamin , Margulies Kenneth B , Ibrahim Michael
Published: December 2023

Background:
Mechanical overload is an established contributor to T-tubule (TT) remodeling and associated dyssynchronous Ca
2+
release leading to abnormal excitation-contraction coupling in cardiomyopathies. We examined the induction of pathological TT remodeling in isolated cardiomyocytes and the involvement of microtubules (MT) in this process.

Methods:
Adult rat ventricular myocytes (aRVMs) were cultured with applied variable
in vitro
load for 48hrs at either physiological (10kPa) or pathological (50kPa) stiffness, using custom magnetorheological elastomers with tunable stiffness. Cells were stained with Di-8-ANEPPS and Fluo-4-AM and imaged using confocal microscopy. Field stimulation of cells allowed for Ca
2+
transient acquisition via line scans. Protein expression changes were determined via Western blotting. IF staining allowed for visualization of the MT network and relevant TT proteins (TCAP, JPH2, BIN1). MT and tyrosination state dependency of remodeling was investigated by 1μM nocodazole (MT depolymerizer), taxol (MT stabilizer), and tubulin tyrosine ligase (TTL) treatments to alter the MT network accordingly.

Results:
Compared to the physiological stiffness group, aRVMs subjected to pathologically increased stiffness exhibited a 14.7% decrease in density, 18.9% decrease in regularity, and a 26.6% increase in luminal dimension of the TT system, along with an increase in longitudinal elements (p<0.05). The changes in both Ca
2+
handling parameters and protein expression resembled those typical of the
in vivo
myopathic phenotype. This included a 21.7% decrease in amplitude, along with a 33.7%, 29.8% and 21.1% increase in time to peak (TTP), variance in TTP, and the signal decay tau, respectively (p<0.05). Treatment of pathologically loaded cells with taxol worsened TT remodeling, specifically with respect to TT density which decreased by 12.5% compared to nontreatment cells, and longitudinal elements which increased by 24%. Increased MT tyrosination through TTL treatment showed a 37% recovery in TT density in cells cultured at pathological stiffness compared to nontreatment cells (p<0.05).

Conclusion:
The results suggest that load-induced TT remodeling occurs via a cardiomyocyte autonomous, MT-dependent mechanism.
Abstract 17001: Enhancing Coronary Functional Angiography: Integrating Doppler-Based Left Circumflex Coronary Flow Reserve in Assessment
Authors: Ashokprabhu Namrita , Roca Alvarez Yulith , Schmidt Christian , Thompson Lauren , Hamstra Michelle , Henry Timothy D , Quesada Odayme
Published: December 2023

Background:
Coronary microvascular dysfunction (CMD), predominantly affecting women is associated with poor outcomes and has limited diagnostic options. Coronary functional angiography (CFA) is used for diagnosing CMD in patients with refractory angina and no obstructive coronary artery disease (ANOCA). The assumption is that endothelial-independent CMD is a homogenous disease process, therefore current gold-standard for diagnosis is measure of coronary flow reserve (CFR) in the proximal left anterior descending artery (LAD). However, there is limited data on CFR in the left circumflex (LCx).

Objective:
Examine the benefits of measuring CFR using Doppler-tipped guide wire in LCx in addition to proximal LAD.

Methods:
Examined 191 ANOCA patients with Canadian Cardiovascular Society (CCS) class 3 or 4 angina despite optimal medical treatment who underwent CFA for assessment of CMD. CFR measurements were obtained using Doppler-tipped guidewire during the administration of 72 mcg of adenosine in both the proximal LAD and LCx and CFR of <2.5 was used to define CMD.

Results:
191 patients underwent CFA including 91% female with a median age of 59 years (IQR: 50, 67). The correlation in CFR measurements between the proximal LAD and LCx was 0.610 (p<0.001). 149 (78%) patients had concordant results including 113 (59%) with abnormal CFRs and 36 (19%) with normal CFRs in both vessels. 12 (6%) had abnormal proximal LAD CFR and normal LCx CFR; and 30 (16%) had an abnormal LCx CFR and normal proximal LAD CFR and would have gone undiagnosed without measuring LCx CFR.

Conclusion:
The addition of LCx CFR measurement to the current standard CFA protocol using the Doppler guidewire improves diagnosis of CMD in patients. Further studies are needed to evaluate a comprehensive assessment of CMD including measurement of LCx CFR.
Abstract 17002: Platelet-Derived Purified Exosome Product to Treat In-Stent Restenosis Porcine Model
Authors: Rizzo Skylar A , Singh Swaiman , Witt Tyra A , Nagel Mary , Stalboerger Paul , Behfar Atta
Published: December 2023

Introduction:
Patients with coronary artery disease (CAD) not amenable to revascularization are reported to have a 3-year mortality >14%. Advances in treatment modalities including medical management, rotational atherectomy, balloon lithotripsy, and drug-eluting stents work for focal disease but poorly treat diffuse CAD. In a porcine model of in-stent restenosis, we here evaluated whether a pro-angiogenic platelet-derived exosome product (PEP) could be delivered into the perivascular space to foster collateral vessel formation.

Methods/Results:
Cobalt chromium stents were placed and were oversized by 1 mm in the left anterior descending (LAD) and posterior descending arteries (PDA) of sus scrofa domesticus pigs. In-stent restenosis was angiographically visualized at the 2-month timepoint, with hemodynamic significance documented with fractional flow reserve (FFR) of <0.8. To document feasibility of PEP delivery into the perivascular space, exosomes were labeled with a far-red fluorescent tag and delivered into the perivascular bed. Here, the Bullfrog® micro-infusion catheter was positioned either in the great cardiac vein or the middle cardiac vein and PEP was delivered with the microneedle pointed towards the LAD or the PDA. Biodistribution demonstrated exosome retention and uptake around cardiac veins. Using the Bullfrog® technique, PEP was delivered in the perivascular space adjacent to areas of significant coronary stenosis. Initial results 1-month post-treatment demonstrated improved FFR of treated stenotic vessels (from 0.68 to 0.85), while untreated vessels demonstrate no change from previous FFR measurement (from 0.79 to 0.78).

Conclusions:
Here, exosome-mediated angiogenesis in the perivascular space improved coronary blood flow, distal to areas of stenosis. In patients with diffuse CAD, delivery of biotherapy in cardiac veins running anatomically parallel to stenosed epicardial arteries provides a novel therapeutic opportunity to supplement the existing armamentarium of therapies available for in-stent restenosis.
Abstract 17051: Oxytocin Receptor in the Spinal Neuraxial Modulation of Ventricular Excitability
Authors: Hellman Abigail , Howard-Quijano Kimberly , Kuwabara Yuki , Salavatian Siamak , Fisher Madison , Mahajan Aman
Published: December 2023

Introduction:
Cardiac sympathoexcitation is a major contributor to the pathogenesis of ventricular tachyarrhymias (VTs) during ischemia reperfusion (I/R) and chronic myocardial infarction (MI). Afferent network connections in the intermediolateral cell column (IML) and dorsal horn (DH) control sympathetic output to the heart. Our team reported spinal cord stimulation (SCS), decreased cardiac sympathoexcitation and reduced VTs during ischemia. Oxytocin (OXT) is a known neuromodulator; however, whether OXT signaling can modulate the cardiospinal neural network is unknown.

Hypothesis:
SCS neuromodulation is reducing sympathoexcitation and VTs through OXT signaling pathways.

Methods:
Two models of cardiac ischemia were used in Yorkshire domestic swine. In acute I/R, a suture was placed around the left anterior descending (LAD) coronary artery, after sternotomy. Chronic infarction (MI) was created by accessing the femoral with fluoroscopy guidance. Polystyrene microspheres (1ml) were injected via a 3mm angioplasty balloon catheter to the LAD. Animals then recovered post-MI for 6-8wk. SCS treatment was delivered through a four-pole lead which was inserted in the epidural space (T1-T4)(50Hz, 0.4ms pulse duration). T2-T4 spinal cord was collected postmortem for molecular analysis. Fluorescence
in situ
hybridization (FISH) protocol for RNAscope Fluorescent v2 Assay (ACD) was followed. Cell counts represented as 3 puncta or more centered around DAPI.

Results:
We report that OXT receptor positive cells significantly decreased as a result of I/R and MI (p<0.001, two-way ANOVA n=4-5 animals, average of 2-3 slices per animal). Within the DH the majority of OXT positive cells were inhibitory GABAergic neurons. Within the IML, a majority of the cells regulated by I/R and MI were microglia, and both an inhibitory and excitatory population contributed to the onset of ischemia. SCS treatment after I/R and MI resulted in the recovery of this OXT receptor cell population.

Conclusions:
By evaluating the role of OXT in reducing cardiac sympathoexcitation at the level of the spinal cord, we provide new insights into optimizing current neuromodulation approaches and developing new pharmacologic therapies.
Abstract 17068: Proportionate Suicide Mortality in Cardiovascular Disease in the United States From 1999 to 2019
Authors: Agrons Kenyon , NAMBI VIJAY , Minhas Abdul Mannan Khan M
Published: December 2023

Introduction:
Few studies have investigated disease associated suicide other than mental health. We aimed to assess suicide mortality in cardiovascular disease.

Methods:
We used CDC WONDER to access National Vital Statistics System data from 1999 to 2019. Suicide and CVD related deaths in patients ≥ 25 years of age were identified from multiple causes of death. Proportionate suicide mortality (PSM) was calculated as number of suicide deaths listed with CVD, divided by number of all cardiovascular-related deaths irrespective of suicide, and reported as PSM per 100,000 cardiovascular deaths. Joinpoint regression was used to examine changes in trend using annual percentage change (APC) overall and by sex, race/ethnicity, disease subtype, and age.

Results:
PSM by disease category from most to least were mental health,, nervous system, musculoskeletal, gastrointestinal, cardiovascular, respiratory, and lastly malignant neoplasm. The CVD PSM increased from 62.8 in 1999 to 90.5 in 2019 (average APC 2.1* [95% CI, 0.2 to 3.9]). Notably, APC decreased from 2013-2019 (APC -2.1 (95% CI -3.6 to -0.5). In racial/ethnic groups, PSM was highest in non-Hispanic White (NHWs) (103.8) then Hispanic/Latino (H/L) (63.6), and lastly NH Black (NHB) (29.2) individuals. PSM was highest in 25-39 years age group (858) followed by 40-54 years (382.8), 55-69 years (146.2), 70-84 years (55.9), and lastly 85+ (17). APC in PSM initially increased in men (3.1 until 2013), women (4.1 until 2014), NHW (3.9 until 2013), H/L (3.5 until 2014), 40-54 (2.9 until 2013), 55-69 (6.0 until 2013) then either stabilized or decreased. While APC in NHBs (1.0) and 25-39 years (1.4) consistently increased till 2019.

Conclusion:
Among non-mutually exclusive disease categories, CVD ranked 3rd to last. PSM in CVD peaked in the early 2010s, with variable increases across various sex, racial/ethnic, and age groups. Further research is needed to understand the causes of these disparities to develop preventative strategies.
Abstract 17070: Dyslipidemia Prevalence Among a Diverse Cohort of Childhood, Adolescent and Young Adult Cancer Survivors
Authors: Dean Matthew , Bane John , Hang Yi , Miller Ericka , Menachery Sherin , Chuquin David , Aston Adam , Deng Xiaoyan , Bandyopadhyay Dipankar , Jordan Jennifer H , Truong Uyen T , Gowda Madhu , Bottinor Wendy
Published: December 2023

Background:
In the general population, dyslipidemia impacts 36% of adults between the ages of 20 and 29 years. Among survivors of childhood, adolescent, and young adult-onset cancer (C-AYAs), the prevalence of dyslipidemia in racially diverse cohorts as well as our understanding of which measured fats are most commonly abnormal are limited.

Question:
Among a diverse group of C-AYAs, what is the prevalence of dyslipidemia and which fats are most contributory?

Methods:
Individuals diagnosed with cancer at age ≤39 years and treated with anthracycline based chemotherapy between 2010-2022 were identified. Depending on age at time of collection, post-treatment lipid panels were analyzed according to AAP (<20 years) or ACC/AHA (≥20 years) guidelines. Non-fasting panels were included, in accordance with ACC/AHA guidelines. The prevalence of dyslipidemia and median values for measured fats were determined. Non-parametric testing was used to examine associations between dyslipidemia, age, and race.

Results:
Among a diverse (40% Black, 52% White) cohort of C-AYAs (227 total) with a median current age of 25 years (interquartile range (IQR) 20-36 years) and median total doxorubicin isotoxic equivalents of 200mg/m
2
(IQR 120-300 mg/m
2
), the prevalence of dyslipidemia was 55%. Prevalence of dyslipidemia was not associated with race (Black 55%, White 64%, Other 44%, p=0.281) or age (<20 years 51%, ≥20 years 64%, p = 0.055). Among Black and White subjects, HDL was most commonly abnormal (Black 42%, White 38%), followed by triglycerides (TG) (Black 29%, White 41%). Median TG levels were significantly lower among Black individuals ≥20 years compared with White individuals (117 mg/dL vs 143 mg/dL, p = 0.030).

Conclusions:
Among a diverse group of C-AYAs, dyslipidemia was highly prevalent even at a younger age (<20 years). Race was not associated with prevalence of dyslipidemia. Dyslipidemia was primarily driven by HDL and TG abnormalities, fats associated with metabolic syndrome.
Abstract 17074: Development and Multinational Validation of a Machine Learning-Based Optimization for Efficient Screening for Elevated Lipoprotein(a)
Authors: Aminorroaya Arya , Dhingra Lovedeep S , Saadatagah Seyedmohammad , Spatz Erica S , Oikonomou Evangelos K , Khera Rohan
Published: December 2023

Background:
Lipoprotein(a) [Lp(a)] is associated with an increased risk of major adverse CV events even among those receiving optimal lipid-lowering therapy. However, <1% of patients with or without ASCVD undergo Lp(a) testing. We developed a machine learning model to optimize screening for high Lp(a) using structured clinical elements.

Methods:
We included 456,815 participants of UK Biobank (UKB), the largest cohort of people who underwent protocolized Lp(a) testing regardless of indication. Potential features spanned demographics, medication history, diagnoses, procedures, vital signs, and lab values from UKB and linked EHR to predict high Lp(a) (≥150 nmol/L). The dataset was split into train and test sets (80:20). We trained multiple extreme gradient boosting models using all available features and selected the best model by prioritizing high AUROC while minimizing the number of features using cross-validation. Pooled cohort equation (PCE) was used as a comparator to predict high Lp(a). We externally validated the model in well-established CV cohorts of ARIC, CARDIA, and MESA (Fig A).

Results:
The best model used features of LDL-C, statin use, triglycerides, HDL-C, ASCVD, and antihypertensive medication use, and outperformed the PCE score for predicting high Lp(a) (AUROC 0.66 vs 0.52, P<0.001). The model performed comparably across ARIC, CARDIA, and MESA cohorts (Fig B). To find 1 person with high Lp(a), the model reduces the number needed to test (NNT) by up to 62% depending on the probability threshold, which can be tailored to different use cases (Fig C). The relative reduction in NNT is higher among those without vs with ASCVD (49% vs 26%, for optimized specificity with a threshold of 0.2).

Conclusions:
Our model optimizes Lp(a) testing strategies using commonly available clinical features, which can be leveraged in EHR and other settings for efficient Lp(a) screening. The model can encourage greater Lp(a) testing and optimize case finding for future studies.
Abstract 17080: Subcutaneous Implantable Cardioverter Defibrillator in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Oliveira Vinicius M , Oliveira Izadora C , da Silva Menezes Junior Antonio
Published: December 2023

Background:
The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to transvenous implantable cardioverter-defibrillator (TV-ICD), mitigating the risks associated with transvenous leads. However, the effects of S-ICD in hypertrophic cardiomyopathy (HCM) remains uncertain. Thus, we performed a systematic review and meta-analysis to assess the efficacy and safety of S-ICD in treating patients with HCM.

Methods:
We systematically searched PubMed, Embase and Scopus on April 2023 for studies comparing S-ICD to TV-ICD in patients with HCM. Key endpoints of interest included incidence of appropriate shocks (AS), inappropriate shocks (IAS), and device-related complications. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed using a random-effects model. Heterogeneity was assessed with I
2
statistics, and a p-value of <0.05 was considered statistically significant.

Results:
We screened 1070 records. Six studies comprising 3,820 patients were included, of whom 2,497 (65.4%) were male. Mean age ranged from 39.1 to 49.4 years. Our pooled analysis indicated that device-related complications were significantly less frequent in the S-ICD group compared with the TV-ICD group (OR 0.39; 95% CI 0.18 to 0.82; p=0.01; Figure 1A). However, the incidences of AS (OR 0.56; 95% CI 0.20-1.57; p=0.27) and IAS (OR 1.26; 95% CI 0.61 to 2.59; p=0.54; Figure 1B) were not significantly different between the two groups.

Conclusions:
These findings suggest that S-ICD are associated with fewer device-related complications as compared with TV-ICD, among patients with HCM. Appropriate and inappropriate shocks are not significantly different between the two strategies.
Abstract 17087: Novel Machine Learning Models to Enhance and Automate Cardiovascular Outpatient Triage for Patients With Atrial Fibrillation
Authors: Kowlgi Gurukripa N , Schaeferle Gavin , Huang Yu-Li , Kuster Lezli , Jensen Maribeth , Madhavan Malini
Published: December 2023

Introduction:
Atrial fibrillation (AF) is the most prevalent arrhythmia, placing a substantial burden on the healthcare system. Patients with AF are cared for in a variety of settings including primary care and cardiology clinics, while some require cardiac electrophysiology (EP) clinics offering specialized drugs or procedures. Appropriate triage of AF referrals to these specific clinics will lead to timely and appropriate care and reduce inefficiency in the health system.
Goal:
To develop a machine learning (ML) model to triage AF referrals to a large Cardiology center to either the Cardiology or EP clinic based on likelihood of requiring an invasive EP procedure or initiation of antiarrhythmic drug.

Methods:
We retrospectively analyzed 6,755 patients who were referred to CV with referral diagnosis of AF (mean age 70 ± 11 years, 66% male). We employed multiple input variables to predict the suitability for EP clinic defined as need for initiating an antiarrhythmic drug or an invasive EP procedure. These encompassed patient demographics, relevant comorbidities, medications, prior procedures, medical notes analyzed using natural language processing (NLP), and Holter monitoring data.

Results:
For internal referrals, XG boost model performed the best with AUC at 79%, accuracy at 72%, and F1 score at 68%. This model produces true positive (TP) at 68% and true negative (TN) at 74%, which was better in comparison with triaging using NLP only (AUC = 69%, TP = 58%, TN = 61%), Holter only (AUC = 52%, TP = 51%, TN = 77%), and NLP/Holter (AUC = 67%, TP = 60%, TN = 60%). When supplementing ML model with Holter readings on average HR ≥ 100 and maximum HR ≥ 150, the results can be improved to TP at 70% and TN at 73%.

Conclusions:
Our model effectively identifies patients who are more likely to require specialized EP care, enabling the automation and increased efficiency of the AF referral triage process. Prospective validation studies are paramount in determining the true value of this tool.
Abstract 17090: Prognostic Value of Creatinine versus Cystatin C-Based Estimation of Glomerular Filtration Rate for Mortality in Heart Failure
Authors: Roehm Bethany , Gordon Jonathan , McAdams Meredith , Grodin Justin L , Hedayati Susan
Published: December 2023

Introduction:
Serum creatinine and cystatin C are filtration markers used to calculate estimated glomerular filtration rate (eGFR). Lower eGFR using both is associated with increased mortality in heart failure with reduced ejection fraction (HFrEF). Cystatin C may be more accurate in advanced HFrEF with sarcopenia. Prognostic ability of each (eGFRcr or eGFRcys) or their weighted average (eGFRcr-cys) has not been compared.

Hypothesis:
eGFRcr-cys is more predictive of mortality in HFrEF than eGFRcr or eGFRcys.

Methods:
We analyzed data from 310 participants from Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with baseline serum creatinine and cystatin C. Primary outcome was all-cause mortality. Cox models were adjusted for age, sex, race, diabetes mellitus, and NYHA class.

Results:
Median eGFR by cr, cys and cr-cys were 60, 58 and 60 ml/min/1.73m
2
. During 2-year follow-up, 45 participants died. Within each patient, the difference of eGFRcr and eGFRcys varied from -49 to 50 ml/min/1.73m
2
. Among all estimates, those with baseline eGFR <60 ml/min/1.73m
2
had worse survival (Figure). Lower baseline eGFRcr [HR 0.97, 95% CI (0.96-0.99), P =0.008, C= 0.67], eGFRcys [HR 0.98 (0.97-0.99), P= 0.006, C= 0.68], and eGFRcr-cys [HR 0.98 (0.96-0.99), P= 0.004, C= 0.68] were associated with higher mortality. C-statistic comparison did not show a significant difference for predictive ability: eGFRcr vs. eGFRcys, P=0.7; eGFRcr vs. eGFRcr-cys, P=0.9; eGFRcys vs. eGFRcr-cys, P=0.3).

Conclusions:
Using all three estimates, lower eGFR was associated with higher mortality, although all had relatively poor predictive performance. eGFRcys was expected to be similar to or lower than eGFRcr due to decreased muscle mass, yet at the individual level there was wide variability between estimates which could in part explain their poor predictive abilities. There is need for more specific kidney filtration markers for prediction of mortality in HFrEF.