bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14214: Visualization and Quantification of Autogenic Cardiac Mechanical Waves
Authors: Moore Cooper , McCrary Andrew , LeFevre Melissa , Barker Piers , Von Ramm Olaf T
Published: April 2024

Introduction:
We have developed a visualization technique, High Speed Difference Imaging (HSDI) that has revealed many rapidly propagating phenomena throughout the cardiac cycle. We observed diastolic and systolic waves in adult volunteers and measured their velocities to determine the nature of the waves. We hypothesize from these early observations that these waves are autogenic shear waves that will propagate at higher velocities in systole.

Methods:
High frame rate ultrasound images were acquired using the T5 System with synchronous EKG. T5 is the Duke University Phased Array Research Ultrasound Scanner that can be configured to acquire real time, live images at rates up to 1000 B-Modes per second for adult cardiac applications. HSDI were generated in 10 volunteers in the AP4 view. A late diastolic shadow that propagated from apex to base in the lateral wall was characterized in all volunteers. A distinct early systolic shadow was able to be isolated in the lateral wall of five volunteers. The velocity of these shadows was calculated by measuring the length of the lateral wall along during its appearance and by counting calibrated timed frames while the shadow was visible.

Results:
The diastolic propagating shadow was observed in all ten volunteers in multiple cardiac cycles. The late diastolic shadow was measured propagating apex to base at an average velocity of 2.5 ± 0.5 m/sec. In the five volunteers with distinct systolic shadows, the propagating velocity was measured to be 4.8 ± 0.7 m/sec. The average ratio of systolic shadow propagation velocity to diastolic in the five patients was 1.95. These propagation velocities are comparable to published myocardial shear wave velocities in humans.

Conclusions:
The propagation velocity of these waves doubles in systole when the myocardial tissue is stiffened, and the velocities measured are within the range of reported shear wave velocities in myocardium. We conclude that high frame rate ultrasound imaging may allow for the visualization and quantification of autogenic cardiac shear waves.
Abstract 14216: Mitochondrial Dysfunction in Aged Hearts: Role of Mitochondrial Calpain Activation
Authors: Chen Qun , Thompson Jeremy , Hu Ying , Lesnefsky Edward J
Published: April 2024

Introduction:
Mitochondrial function is impaired in aged hearts. Calpain 1 (CPN1) is a calcium-dependent cysteine protease located in cytosol (cCPN1) and mitochondria (mCPN1). Activation of CPN1 contributes to mitochondrial dysfunction during ischemia-reperfusion. Induction of acute ER (endoplasm reticulum) stress causes CPN1 activation in adult hearts. We find that aging leads to increased ER stress that may favor CPN1 activation.

Hypothesis:
ER stress induced CPN1 activation leads to mitochondrial dysfunction during aging.

Methods:
Male adult (3 mo.) and aged (24 mo.) mice were provided by NIA. 4-PBA (1g/kg/day) was dissolved in drinking water with sucrose (0.2 g/100 ml) as sweetener. Sucrose water was used as vehicle control. Mice were treated for two weeks with 4-PBA or vehicle followed by the isolation of cardiac cytosol, SSM (subsarcolemmal mitochondria) and IFM (interfibrillar mitochondria).

Results:
Oxidative phosphorylation was decreased in IFM from 24 mo. compared to 3 mo. when glutamate + malate was used as complex I substrate (Fig A). The 4-PBA treatment improved oxidative phosphorylation in aged IFM (Figure A). The cCPN1 was activated in 24 mo. as shown by increased spectrin cleavage (Figure B). The α1 subunit of pyruvate dehydrogenase (PDH) is a substrate of mCPN1. The content of the PDH α1 subunit was decreased in 24 mo. compared to 3 mo., indicating that the mCPN1 was activated during aging (Figure C). The 4-PBA treatment decreased the activation of cCPN1 and mCPN1 in aged mice. SSM function is also impaired during aging (data not shown).

Conclusions:
Aging increased the activation of both cCPN1 and mCPN1. Attenuation of ER stress in 24 mo. mice using 4-PBA decreased cCPN1 and mCPN1 activation. Decreased CPN1 activation was accompanied by improved mitochondrial function . The results support that activation of calpain 1, most likely mCPN1, is a likely cause of increased mitochondrial dysfunction during aging.
Abstract 14230: Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity
Authors: Alves De Souza Rodrigo W , Gallo David , Levy Howard , Gomperts Edward , Young Mark , Gomperts Andrew , Otterbein Leo E
Published: April 2024

Introduction:
Doxorubicin (DOX) and other anthracyclines comprise important anticancer drugs. However, anthracycline treatment-related cardiotoxicity is a major clinical problem for which there are currently no effective treatments. Low-dose carbon monoxide (CO) presents an exciting and promising approach to preventing anthracycline cardiotoxicity. Endogenous CO is generated in the body by heme oxygenase enzymes during the degradation of heme. There is a literature precedent that supports low-dose CO in providing cardioprotection without reducing DOX efficacy.

Hypothesis:
the present study aimed to test an oral formulation of CO (HBI-002) to attenuate DOX-induced cardiotoxicity.

Methods:
Male C57BL/6, 10 to 12-week-old mice were subjected to acute (single dose, 20mg/kg, i.p.), and chronic (ten doses, 2mg/kg, i.p., every other day) DOX regimens in combination with HBI-002 (10ml/kg) or vehicle (10ml/kg). Animals were sacrificed after one hour of single DOX injection to evaluate serum tissue damage markers, such as creatine kinase (CK), lactate dehydrogenase (LDH), and heme. Moreover, cardiac function was evaluated after seven days of single DOX injection and after a chronic DOX regimen by echocardiography.

Results:
Here, we show that after DOX injection, HBI-002 can prevent a rapid and early release of excess serum CK (Vehicle: 2547 ± 260 U/L vs. HBI-002: 1122 ± 168 U/L;
p<0.05
), LDH (Vehicle: 1390 ± 103 U/L vs. HBI-002: 1122 ± 168 U/L;
p<0.05
), and heme (Vehicle: 47.5 ± 6.7 uM vs. HBI-002: 5.3 ± 2.7 uM;
p<0.05
) levels. Moreover, we observed that HBI-002 prevented a decrease in the ejection fraction after seven days of a single dose of DOX (Vehicle: 54.3 ± 1.3% vs. HBI-002: 64.7 ± 7.5%;
p<0.05
), as well as after DOX chronic regimen (Vehicle: 44.5 ± 3.6% vs. HBI-002: 61.6 ± 5.4%;
p<0.05
). Finally, HBI-002 attenuated DOX-induced mortality compared to the vehicle-treated group.

Conclusions:
Collectively, these findings support HBI-002 as a promising cardioprotective agent against DOX toxicity and warrant further development as a therapeutic.
Abstract 14234: Stroke Center Volume, Not Accreditation Status, is Associated With Outcomes of Stroke Patients Treated by Mechanical Thrombectomy
Authors: Waqas Muhammad , Patel Tatsat Rajendra R , Cappuzzo Justin , Levy Bennett R , Davies Jason M , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H , Tutino Vincent M
Published: April 2024

Introduction:
In the USA, endovascular capable stroke centers (ECC) that perform mechanical thrombectomy (MT) for large vessel stroke can be accredited by a number of agencies. However, there remains little evidence on recommendations for minimum case volume required for centers to maintain competency.

Hypothesis:
Clinical outcomes (namely hospital mortality and home discharge disposition) of stroke patients treated by MT are associated with center volume but not accreditation status.

Methods:
We obtained nationwide MedPAR data from the Center for Medicare and Medicaid Services (CMS) for 2017 and 2018. Endovascular MT cases were identified using ICD 10 codes. A list of ECCs was obtained from the Joint Commission, HFAP, DNV, and State Health Departments and was cross-referenced with a list of accredited centers. Independent t-tests were used to compare the mean rates of mortality and home discharge between accredited and non-accredited centers. Pearson’s correlation was used to test the association of annual case volume (in 10 groups in logarithmic increments from minimum to maximum) with the rates of mortality and home discharge.

Results:
In 2017 and 2018, we identified 29,536 cases of MT that were performed at 847 centers (of which 354 were accredited) across the USA. There was no significant difference between accredited and non-accredited centers with regard to hospital mortality (14.8% vs. 14.5%, p-value=0.34) and home discharge disposition (12.1% vs. 12.0%, p-value=0.78). Hospital mortality was significantly negatively correlated with center volume (r=-0.83, 95%CI=-0.96 to -0.44, p-value=0.003), whereas home discharge disposition was significantly positively correlated with center volume (r=0.68, 95%CI=0.09 to 0.92, p-value=0.030).

Conclusions:
Accreditation showed no correlation to clinical outcomes. However, increasing volume of MT cases in ECCs correlated to increasing mortality and decreasing rate of home discharge.
Abstract 14237: Myocardial Work Indices by Pressure-Strain Loop Analyses Predict Cardiovascular Outcome in the General Population
Authors: Olsen Flemming J , Skaarup Kristoffer G , Lassen Mats H , Johansen Niklas , Schnohr Peter , Jensen Gorm B , Marott Jacob , Sogaard Peter , Aalen John , Remme Espen W , Smiseth Otto A , Mogelvang Rasmus , Biering-Sørensen Tor
Published: April 2024

Introduction:
A novel tool to assess myocardial work by echocardiography has recently become available through pressure-strain loop (PSL) analyses. We sought to evaluate the prognostic value of non-invasive myocardial work indices in the general population.

Methods:
This was an echocardiographic substudy based on a prospective community-based cohort study (n=4,466). PSL analyses were performed to acquire myocardial work index (MWI), global constructive work (GCW), global wasted work (GWW), and myocardial work efficiency (MWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD) at 5-years of follow-up. Multivariable logistic regression was applied to adjust for SCORE chart risk factors. Spline curves were constructed with Poisson regression.

Results:
A total of 3,896 participants were included in this analysis (mean age: 56 years, 43% men). Of these, 232 (6%) experienced the outcome within 5 years. Participants who experienced HF/CVD had reduced MWI (2202 vs. 2295mmHg%, p=0.001), reduced MWE (95.8 vs. 96.9%, p<0.001), and higher GWW (95 vs. 73mmHg%, p<0.001), whereas GCW was similar between outcome groups. In addition, decreasing MWI and MWE as well as increasing GWW was associated with a higher risk of HF/CVD in univariable analyses. After multivariable adjustments, however, all work parameters were associated with HF/CVD (MWI: OR=1.15 (1.10-1.19), per 100mmHg% decrease; GCW: OR=1.14 (1.10-1.19), per 100mmHg% decrease; GWW: OR=1.19 (1.05-1.34), per 50mmHg% increase; MWE: OR=1.14 (1.08-1.19), per 1% decrease). The risk of HF/CVD was curvilinear for MWI and GCW, whereas there was a linear association for GWW and MWE (figure).

Conclusions:
Myocardial work indices by PSL analysis are associated with 5-year risk of HF/CVD in a large-scale general population independently of clinical risk factors.
Abstract 14249: Response to Cardiac Resynchronization Therapy in Cancer Patients With Heart Failure
Authors: Schubert Scott R , Karimzad Kaveh
Published: April 2024

Introduction:
Heart failure is associated with poor clinical outcomes in cancer patients. Cardiac resynchronization therapy (CRT) provides a therapeutic avenue to improve left ventricular function and decrease symptoms. Historically, CRT has been underutilized in cancer patients. We assessed the hypothesis that cancer patients have a similar response to cardiac resynchronization therapy as the general heart failure population.

Methods:
This study included 37 patients with cancer who underwent CRT implantation between 2012 and 2020. The primary endpoints were response to CRT as measured by an improvement in left ventricular ejection fraction (LVEF) by >=10% or decrease in left ventricular end systolic volume index (LVESVi) by >=15% over 3 to 24 months. Secondary endpoints were change in LVEF, LVESVi, and New York Heart Association (NYHA) class.

Results:
Of 37 patients, primary and secondary endpoints were available for 34 patients (mean [SD] age, 68 [9] years; 24 men (71%); 26 nonischemic cardiomyopathy (76%), 8 ischemic (24%); mean QRSd 152 ms; 10 patients with NYHA II symptoms (29%), 24 NYHA III (71%)). 20 patients met the primary endpoint (65% [46%-80%]). This response rate is not significantly different than published response rates to CRT of 70% in the general heart failure population. The average improvement in LVEF was 12.9% ([9.4%-16.4%], p<0.001). The average decrease in LVESVi was 25.4% ([17.2%-33.5%], p<0.001). 23 of 34 patients had an improvement in NYHA classification (20 by one class, 3 by two), whereas 9 patients had no improvement and 2 patients had worsening symptoms (mean improvement 0.7 [0.46-0.96], p<0.001). 2 of 37 patients had a complication (one late device infection, one right atrial lead dislodgment requiring reimplantation). 4 of 37 patients (10.8%) died within 12 months of primary oncologic cause. 4 of 34 (11.7%) CRT-D patients had received appropriate therapies on device interrogation at time of submission.

Conclusions:
CRT improves left ventricular function, reverses left ventricular remodeling, and improves exertional dyspnea in patients with cancer. Response rate is similar to that of a general heart failure population. Oncologic prognoses of over 12 months life expectancy at time of implant were reasonably accurate.
Abstract 14250: Innovative Model-Based Algorithm for Non-Invasive Estimation of Pressure-Volume Loops in Patients With Cardiogenic Shock
Authors: Sacchi Stefania , Sabatini Antonella , VENUTI ANGELA , cinel elena , Gattari Bianca , Baldetti Luca , Calvo Francesco , Gramegna Mario , Pazzanese Vittorio , Cappelletti Alberto Maria
Published: April 2024

Introduction:
Cardiogenic shock (CS) pathophysiology may be well explained through the left ventricular pressure-volume (PV) loops.

Hypothesis:
We developed an innovative model-based algorithm to derive non-invasive left ventricular PV loops and we assessed its ability to provide information in CS patients.

Methods:
We conceived and implemented a simple, intuitive and practical model-based algorithm for the non-invasive left ventricular PV loop diagram visualization and analysis. This model is based on the quantitative numerical calculation of the product of two time-varying curves, namely the LV volume V(t) multiplied by the time varying LV elastance function, in order to obtain the time varying LV pressure curve, according to the well-known relation: P(t) = E(t) * V(t) [formula F1] [Seeman et al. 2019]. The algorithm works as follows: 1) Input parameters: HR, EDV, ESV, Estimated LV elastance value for healthy (control) and for pathologic subjects. 2) Picked qualitative illustrations exhibiting time-varying dynamics of:a. Normal LV Elastance b. Normal LV Volume 3) Digitized, appropriately scaled, and adapted to input, curves in step (2).4) P(t) obtained by applying formula (F1) in Excel spreadsheet.5) Construction of the PV Loop diagram in Excel spreadsheet.

Results:
To test the algorithm, non-invasive input parameters were collected in a patient with CS due to acute myocarditis and in a normal subject. In the CS patient, HR, ESV, EDV were 83bpm, 228 ml and 200 ml, respectively; while in the normal subject, they resulted as 86 bpm, 110 ml, and 45 ml, respectively. In the CS patient, the non-invasive derived PV diagram was significantly different from that assessed in the control subject and exhibited an abrupt reduction of ventricular contractility.

Conclusions:
This novel model-based algorithm provides reliable non-invasive left ventricular PV diagrams in CS patients.
Abstract 14266: Outcomes of Chest Pain Patients Following Application of a Validated High Sensitivity Troponin Algorithm: Comparison of 30 Day Death/ MI of Algorithm Concordant vs Discordant Discharges
Authors: Khan Ayesha , Saleem Muhammad Sabih S , Willner Keith , Sullivan Luke , Matsumura Martin E
Published: April 2024

Introduction:
High sensitivity troponin (hsTn) assays effectively risk stratify patients with chest pain when a validated serial algorithm is utilized. Most of these algorithms require multiple draws for initial values in an intermediate range below a cutoff considered unequivocally consistent with MI. Little is known regarding outcomes of patients who are discharged following deviation from these algorithms.

Hypothesis:
Minor deviation from a validated hsTn algorithm may yield unacceptable outcomes in chest pain patients.

Methods:
Retrospective review of outcomes in patients presenting with chest pain to Geisinger Health System emergency departments and discharged based on application of a validated 0/1/3 hour hsTroponinT (hsTnT) algorithm over a 2-year period. We compared 30-day death/MI in patients who had hsTnT results that were consistent with “ruling out” (algorithm concordant) vs those who were discharged despite either equivocal hsTnT results or incomplete application of the algorithm (algorithm discordant). Patients who were admitted or met criteria for MI based on a peak hsTnT
>
52ng/L were excluded.

Results:
Out of 10,342 patients discharged after hsTnT algorithm, 1,166 (11.3%) were algorithm-discordant. Thirty-day death/MI occurred in 13 (0.14%) of patients managed protocol concordant and 16 (1.37%)of patients managed protocol discordant (p<0.001). The 16 discordant pts with death/MI were algorithm-discordant due to either having only a single hsTnT draw (12) or a 0-1hr delta
>
5ng/L (4). Comparing all patients with vs without 30day death/MI, univariate predictors included median age (66 vs 50yr, p<0.0001), prior CAD history (41.4 vs 17.5%, p=0.002), hyperlipidemia (44.8 vs 21.8%, p=0.006) and hsTnT algorithm discordance (55.2 vs 11.1%, p<0.001). A multivariable logistic regression model found that among univariate predictors only algorithm discordance was an independent predictor of 30-day death/MI (OR 6.42, p<0.001).

Conclusions:
Deviation from an hsTnT algorithm was associated significantly with increased 30 day cardiac events. This study highlights the importance of maintaining concordance with algorithm details when using hsTnT assays to triage chest pain patients.
Abstract 14271: TLR3 as a Potential Target to Prevent Aortic Valve Stenosis
Authors: Willemsen Nicola , Niepmann Sven , Boucher Ann Sophie , Zimmer Sebastian , Nickenig Georg
Published: April 2024

Aortic stenosis (AS) is the most common valvular disease in the western world and is associated with severe morbidity and mortality. Our current concept of disease development suggests that local chronic inflammation drives fibrosis and calcification of the valve cups. It has recently been proposed that activation of pattern recognition receptors may be critical in this context. In a preliminary screening, we found Toll-like receptor 3 expression increased in human AS samples.

Aim of this study was to investigate the role of TLR3 in the pathogenesis of AS.

Isolated human valvular interstitial cells (VICs) were cultured and stimulated with the TLR3 agonist Poly I:C. To inhibit TLR-3 activation, a knockdown was performed using TLR3 small interfering RNA (siRNA) as well as the TLR3/ RNA Complex inhibitor C4a. Calcification was induced by changing the culturing media. RNA was isolated for gene expression analysis. Calcification was visualized by alizarin red staining. Wild type as well as TLR3 knockout mice underwent an ultrasound guided wire injury. After surgery, C4a was injected in WT mice to suppress TLR3 signaling. Valves were explanted and stained with hematoxylin/eosin or anti CD68. Upon stimulation of TLR3 with PolyI:C, TLR3 expression was consistently upregulated in VICs while incubation of VICs with the TLR3/ RNA complex inhibitor C4a resulted in a downregulation of TLR3. These results suggest that TLR3 may be subject to a potential detrimental positive feedback loop in these cells. Importantly, activation of TLR3 led to a marked increase in expression of the pro-osteogenic markers BMP-2 and RUNX2. TLR3 inhibition or knockdown blunted this response.TLR3 deficient mice revealed a significantly smaller aortic valve leaflet area as well as a reduced intravalvular infiltration with monocytes compared to WT. C4a treatment resulted in lower trans-aortic valve peak velocity levels. Further, C4a mice failed to develop AS upon injury.

These findings not only support the endogenous role of TLR3 in the development of AS but suggest that specific TLR3 inhibition might be beneficial for the treatment or prevention of AS. Further studies are required to test this hypothesis and to decipher the exact mechanisms how TLR3 contributes to AS.
Abstract 14283: Metabolic Adaptations of the Maternal Heart During Pregnancy and Postpartum
Authors: Collins Helen E , Fulghum Kyle , McNally Lindsey , Foster Mallory Z , Brittian Kenneth , Chariker Julia , Uchida Shizuka , Lorkiewicz Pawel , Jones Steven P , Hill Bradford G
Published: April 2024

During pregnancy, the maternal heart undergoes reversible, physiologic growth, which supports cardiac output and maintains the physiologic demands of the growing fetus and mother; however, the molecular processes underlying pregnancy-induced cardiac growth are unclear. It is well known that changes in metabolism influence cardiac remodeling, and reductions in pyruvate dehydrogenase activity and cardiac glucose oxidation have been associated with cardiac growth during pregnancy. Therefore, the goal of this study was to examine the underlying metabolic processes that contribute to the structural and functional adaptations of the heart to pregnancy. Timed pregnancy studies in 12-week-old female FVB/NJ mice showed that heart weight to tibia length (HW:TL) was increased throughout the duration of pregnancy with HW:TL being higher in mid-pregnancy (MP, 8 d pregnant), late-pregnancy (LP, 16 d pregnant), and in 1-week post birth (PB) mice versus non-pregnant, diestrus controls (NP). This hypertrophic phenotype was associated with increased myocyte cross sectional area and with significant increases in end systolic and diastolic LV volumes
.
Of note, we found that blood glucose levels (115 ± 4 v 151 ± 6 mg/dL;
p
<0.0001) were reduced at LP versus NP. RNA-seq analyses and downstream immunoblot validation revealed changes consistent with reduced cardiac glucose catabolism at LP. Specifically, we found that
Pdk4
transcript and protein expression (1.00 ± 0.22 v 1.68 ± 0.08; LP v NP;
p
<0.03) were significantly increased at LP and phosphorylation of PFK2 was significantly reduced at LP (1.00 ± 0.12 v 0.48 ± 0.06;
p
<0.01) versus NP. Because inhibition of cardiac glucose oxidation may spare glucose-derived carbon for synthesis of cellular building blocks to facilitate cardiac growth using stable isotope resolved metabolomics, we found that pregnancy increased
13
C-glucose-derived carbon allocation to glycerophospholipids and amino acids suggesting that demand for biosynthetic pathway end products during pregnancy is met in part by ancillary biosynthetic pathways of glucose metabolism. Together, these findings support the hypothesis that changes in metabolism contribute to structural and functional adaptation of the heart during and after pregnancy.
Abstract 14286: Crosstalk Between Methylglyoxal and Acetylation Modifications on Actin, Myosin, and Myosin Light Chain Proteins Affects Sarcomere Functionality
Authors: Delligatti Christine E , Papadaki Maria , Martin Thomas , Kirk Jonathan A
Published: April 2024

Diabetes affects ten percent of Americans. Risk of developing heart failure in these patients is doubled, independent of coronary artery disease and hypertension. However, the mechanistic connection between these two diseases is poorly understood. We have shown one connection is likely due to methylglyoxal (MGO), a highly reactive glycolysis product that can irreversibly modify lysine and arginine residues, a process called glycation. Moreover, we found MGO glycation of the myofilament decreased both calcium sensitivity and maximum calcium activated force (Fmax). Here, we hypothesized that MGO may also negatively impact function by competing for lysine residues that would otherwise be targets for acetylation, which has been shown to be beneficial to cardiac function. Using non-failing human left ventricular (LV) myocardial tissue that had been exposed to acute treatment of MGO (500 μM) or vehicle and subsequently treated with a high dose of acetic anhydride in acetonitrile (300μM) overnight, we found that compared to the vehicle treated samples, MGO inhibited overall acetylation, suggesting that these two PTMs do compete for a subset of lysine residues in the heart. Next, we compared mass spectrometry data sets from diabetic humans, MGO treated mouse myocytes, and acetylated myocytes to identify the specific overlapping residues that acetylation and glycation compete for. This analysis identified multiple sites of crosstalk on actin, myosin, and myosin light chains - proteins essential for normal contractile function. Our preliminary data support a contractile consequence to this crosstalk. Incubation of mouse LV isolated skinned myocytes with acetic anhydride in acetonitrile (300μM, overnight) increased both calcium sensitivity and Fmax. However, exposure to MGO first (500μM) blocked these beneficial functions acetylation (300μM, overnight) in mouse myocytes. Together, we believe these data demonstrate that glycation and acetylation do compete for residues in the myofilament, and that glycation is capable of blocking the beneficial functional effects of protein acetylation. If these results are confirmed and extended
in vivo,
they could have important consequences in diabetes and in the utility of using HDAC inhibitors clinically.
Abstract 14287: Outcomes of Sudden Cardiac Arrest in Liquid vs Solid Cancers. A Nationwide Inpatient Sample Analysis
Authors: sattar yasar , Song David , Syed Fawaduzzaman , Murtaza Fatir , Latchana Sharaad , Zghouzi Mohamed , Ullah Waqas , Alraies M C
Published: April 2024

Background:
The comparative outcomes of Liquid and Solid cancer in Sudden cardiac arrest (SCA) population is not well studied in literature.

Methods:
The National inpatient sample database from the year 2015-2018 was used to compare liquid cancer and Solid cancer patients that underwent sudden cardiac arrest (SCA). Means and medians were calculated for continuous variables,
p
-value (<0.05), and Pearson chi-square used to calculate weighted outcomes.

Results:
A total of 7,695.00 SCA patients (solid cancer n= 475.0 ; liquid cancer n=7,220.0) were included in our study analysis. Among participants, male and female percentages in Solid (65.3 % and 34.7%) and liquid cancers (61.9% and 38.1%) respectively. The median age of solid cancer with SCA was 67 years (IQR 51-77) while median age for liquid cancer with SCA was 70 years (IQR 58-79). The median length of stay of solid cancer with SCA is 8 days (IQR 3-20) whereas liquid cancer with SCA is 5 days (IQR 1-13). There was no statistical significant difference among solid or liquid cancer with SCA in terms of in-hospital mortality (76.6% vs 78.1%,
p =
0.742), acute kidney injury (55.8% vs 61%,
p =
0.319), major bleeding

(5.3% vs 10.7%,
p =
0.098), transfusion requirement (82.1% vs 81.2%,
p =
0.837), and cardiogenic shock (3.2% vs 3.6%,
p=
0.824) in sudden cardiac arrest (SCA) patients respectively. There was higher prevalence of cerebrovascular accidents (3% vs 7.4%,
p=
0.024) and mechanical circulatory support use including ventricular assist devices (VAD) and Extracorporeal membrane oxygen (ECMO) in liquid cancer patients as compared to solid cancers in SCA (1.1% vs 3.3%,
p =
0.001).

Conclusion:
Liquid cancers with SCA can have higher prevalence of stroke and mechanical circulatory support requirement as compared to solid cancers with SCA
Abstract 14290: Implementation of a Comprehensive STEMI Protocol Improves Key Process Metrics for Transfer STEMI Patients
Authors: Zinoviev Radoslav , Kumar Anirudh , Huded Chetan , Johnson Michael , Kravitz Kathleen A , Reed Grant W , Krishnaswamy Amar , Kralovic Damon M , Hustey Fredric M , Brown Abigail S , Kapadia Samir R , Khot Umesh N
Published: April 2024

Introduction:
Despite improvements in STEMI door-to-balloon time (D2BT), the majority of patients who present to US hospitals without PCI capability do not achieve the national goal D2BT of ≤ 120 minutes for transfer STEMI patients. We sought to determine the impact of a comprehensive STEMI protocol (CSP) on key process and outcome metrics in transfer STEMI patients.

Methods:
The CSP is a 4-step STEMI protocol aimed at minimizing STEMI care variability. The protocol streamlines STEMI care by (1) allowing catheterization lab activation by emergency physicians without cardiology consultation, (2) standardizing early administration of guideline-directed medical therapy (GDMT), (3) ensuring immediate transfer to a PCI-capable facility, and (4) implementing a radial artery-first approach (RAFA). We evaluated outcomes in 499 STEMI patients transferred to our hospital from January 1, 2011 to July 14, 2014 prior to implementation of CSP (control group) and 775 patients presenting from July 15, 2014 to July 15, 2019, after implementation of the CSP.

Results:
Compared to the control group, after implementation of CSP there was a significant increase in the number of STEMI patients transferred to our hospital who received GDMT (84.6% vs 93.9%, p<0.001). There was a significant increase in the use of RAFA (19.0% vs 77.7%, p<0.001). The median D2BT decreased from 114 minutes prior (IQR 94.0-146.0min, p<0.001) to 97 minutes (IQR 82.0-115.0min) after CSP implementation, with substantially more patients reaching the target D2BT of 120 minutes (55.7% vs 80.1%, p<0.001). There was a trend towards lower in-hospital mortality after CSP implementation (4.4% vs 2.8%, p=0.180) though the results were not powered to show statistical significance.

Conclusion:
The CSP significantly improved STEMI care key process metrics (GDMT, RAFA, and D2BT) with a trend to lower mortality for patients presenting with STEMI to outside facilities who are transferred to a CCF PCI-capable hospital.
Abstract 14294: Quantification Correction for Rapid Myocardial T1ρ Mapping in Mice Using the T1ρ* Relaxation Pathway
Authors: Gram Maximilian , Gensler Daniel , Winter Patrick , Arias-Loza Anahi-Paula , Jakob Peter M , Nordbeck Peter
Published: April 2024

Introduction:
Cardiac MRI offers detailed tissue characterization and high sensitivity to macromolecules using T
1ρ
based imaging. However, fast and accurate T
1ρ
mapping in the myocardium is still a major challenge in small animal models. The sequence design based on prospective triggering and breath gating causes a corruption of T
1ρ
relaxation leading to quantification errors in the in vivo experiment. In this study, we present a T
1ρ
quantification correction using the T
1ρ
*
relaxation pathway.

Methods:
A new signal equation was derived by analytical means describing spin-lock prepared fast gradient echo readouts: S(t
SL
) = S
0
/ [ exp(t
SL
/T
1ρ
) - cos(α)
NR
exp(-(N
R
T
R
+T
rec
)/T
1
) ] The equation was validated in phantom experiments and used in vivo for corrected T
1ρ
mapping in mice. Here, the correlation of T
1ρ
and the breath dependent spin recovery time T
rec
was examined. The results were compared to the conventional monoexponential T
1ρ
fitting.

Results:
In the phantom study, the novel signal equation provided improved quantification accuracy compared to monoexponential fitting. The mean quantification error could be reduced from -7.4% to -0.97%. In vivo, a correlation of T
1ρ
with the respiratory cycle was observed for monoexponential fitting (PCC=0.804). Using the new correction method, this correlation was reduced (PCC=0.495) and the standard deviation was decreased from ±4.2% to ±1.3%.

Conclusions:
Our corrected formalism enables fast and accurate T
1ρ
quantification for small animals and can improve the comparability of study results. The new technique thus offers a reasonable tool for assessing myocardial diseases. Besides, the derived signal equation could be used for sequence optimization or for subsequent correction of study results.
Abstract 14295: Exploratory Findings Of A Quality Improvement Collaborative To Optimize Care Provided To Heart Failure Patient In A Network Of Heart Failure Clinics In Argentina
Authors: Garcia-Elorrio Ezequiel , Jorro-Barón Facundo , De la Vega Bibiana , Ditata Fernanda , Facta Alvaro D , Flores David , Fernández-Nievas Simón , Fernández Alberto , Mastantuono Cristian , Saa Raquel , San Damaso Esteban , Vega Gustavo , Suarez-Anzorena Inés , Vita Tomás
Published: April 2024

Introduction:
The in-patient management of heart failure (HF) in Argentina has shown profound gaps in performance. Measurement and feedback as well benchmark comparisons showed increase in the use of evidence-based therapies, adherence to performance measures, and shortened lengths of stay in patients hospitalized with HF. Quality improvement collaboratives (QICs) have been used to improve health care for several decades. Our aim was to adopt a HF discharge bundle of care in 50% of enrolled subjects on discharge will reduce readmission by 10%.

Methods:
we are conducting a learning QIC, evaluated through a before-after design, from august 2020 to may 2021 (interim analysis), in 8 HF clinics of Argentina, where patients with newly diagnosed or known HF (LVEF <40%) were enrolled when their discharge process was started after an hospital admission. We implemented a HF bundle of care based on four categories that comprised 12 specific interventions: medication, continuum of care, lifestyle habits, pre-discharge exams. Local hospital teams were trained in improvement and change facilitation. The implementation of the bundle was laid out along 8 learning sessions and periods of action using Plan-Do-Check-Act-cycles and an online platform to register interventions and performance.This an ongoing collaborative to be ended in July 2021. IRB approval was granted in all sites.

Results:
we enrolled 84 patients during baseline (BP) and 96 patients so far after the start of the intervention (IP). No differences were observed related to age, sex, morbidities and left ventricular ejection fraction (LVEF) between periods. Few more patients had history of stroke in the IP period (BP 3.6% vs IP 9.3%, p<0.001). There wasn’t a statistical difference in the accomplishment of all the items of the intervention -all or nothing approach- (BP 10.7% vs IP 17.7%, p=0.183). However, there was a difference in the continuum of care category (BP 27.4% vs IP 53.6%, p<0.001). No differences were observed in the rate of readmissions (BP 8.3% vs IP 3.8%, p=0.231).

Conclusions:
Initial results of a QIC to improve care before discharge of in-patients with HF NYHA class II-III showed an increase in the adoption of an evidence based practices bundle and no changes were observed in the rate of readmissions.
Abstract 14302: Noninvasive Detection of Cardiotoxicity Induced by Chemotherapeutic
Authors: Afrin Humayra , Nurulhuda Md , Islam Tamanna , Nurunnabi Md
Published: April 2024

Introduction:
Cardiac toxicity is one of the most common side effects of many anticancer drugs. Heart damage due to chemotherapy-induced cardiotoxicity can increase the risk of death from cardiac-related causes and reduce quality of life.

Hypothesis:
We hypothesize that Vascular Cell Adhesion Molecule 1 (VCAM1), a biomarker overly expressed within heart when a someone treated with doxorubicin (DOX) due to induction of inflammation within the epithelial cells. In this study we aimed to develop a Vcam1 peptide-based imaging nanoprobe to detect and visualize the cardiotoxicity induced by DOX.

Method:
PLGA-VCAM1-RhB nanoprobe was synthesized using oil in water emulsion method. Size, zeta potential and stability of the probe was measured both in PBS, and PBS with 10% FBS. For in-vitro study Human Cardiomyocyte Cell (HCM) were treated with 0.5μM of DOX for different time period (24 , 48 and 72 hr) to create the inflammation. Toxicity was confirmed by MTT, live dead assay, western blotting, and morphological changes. For in-vivo study 5 mg/kg DOX was injected via tail vain once a week for 3 weeks. After one week of the last dose 100 μg of PLGA-VCAM1-RhB and RhB was injected via tail vain and images were taken at 4 hour of post administration.

Results:
The nanoprobe was found to be stable both in PBS and in 10% FBS solution. Selective binding and higher accumulation of nanoprobe was detected in DOX treated cell compared to the untreated cell and accumulation content was directly proportional to the duration of treatment. In in-vivo study we found higher fluorescent signal in the DOX treatment group than control (RhB and healthy). We also confirmed the results, by measuring the fluorescence intensity of homogenized cardiac tissue by UV-spectrophotometry.

Conclusion:
VCAM1-linked nanoprobe was able to detect Vcam1 expression in inflamed cardiac muscle cell. Hence, we can conclude that Vcam1 is overexpressed in DOX induced cardiotoxicity and our nanoprobe is a potential tool to visualize the damaged area of heart in real time.Abbreviation: PLGA - poly(lactic-co-glycolic acid), RhB- Rhodamine B
Abstract 14305: Diastolic Dysfunction and Activation of Ventricular and Atrial Unfolded Protein Response in a Novel Gottingen Miniswine Model of Heart Failure With Preserved Ejection Fraction
Authors: Sharp Thomas E , Blackwood Erik A , Scarborough Amy L , Glembotski Chris C , Lefer David J , Goodchild Traci T
Published: April 2024

Introduction:
During cardiac hypertrophy, the unfolded protein response (UPR) is activated which includes upregulation of chaperones to assist with protein folding and protein ubiquination for proteolytic degradation. We investigated the expression level of a key chaperone Hspa5 (heat shock protein A5) and ubiquinated protein levels in left ventricular (LV) and atrial (LA) tissue obtained from a preclinical porcine model heart failure with preserved ejection fraction (HFpEF) involving obesity and hypertension.

Methods:
Female Gottingen minipigs were fed standard or western diet (WD) for 20 weeks to induce obesity and metabolic syndrome and subsequent HFpEF. Those fed WD were also administered 11-deoxycorticosterone acetate (DOCA) (50 mg/kg, SQ) to induce hypertension. LV functional assessment was performed via transthoracic echocardiography and invasive hemodynamics at 20 weeks. In addition, UPR and proteasomal function were assayed following 20 weeks of HFpEF in ventricular and left atrial extracts via RT-qPCR and immunoblot.

Results:
Minipigs fed WD+DOCA demonstrated hypercholesterolemia, hypertension, LV hypertrophy and increased LVEDP. LVEF was >50% in HFpEF and control groups. We observed significant LV diastolic dysfunction as measured by E/e’ and LA dysfunction as decreased LA fractional area of change (LAFAC) at 20 weeks. LV extracts from HFpEF swine demonstrated a marked increase in Hspa5 without measurable increases in standard fetal genes (e.g.
Myh7
). LA extracts from HFpEF swine exhibited robust accumulation of ubiquitylated proteins compared to control swine. There was a positive correlation between Hspa5 and E/e’ ratio, and the inverse for LA ubiquitylated proteins and LA function.

Conclusions:
Coordinate with myocardial stiffening, hypertrophy and functional decline, HFpEF robustly augments proteostasis in both LV myocardium and LA recapitulating the clinical presentation of HFpEF patients.
Abstract 14306: Sex Differences in GC1-cGMP Related Cardioprotective Mechanism for Right Heart Failure in Mice Subjected to Right Ventricular Pressure Overload
Authors: Fukuma Nobuaki , Russo Ilaria , Tzimas Christos , Dun Wen , Tsai Emily
Published: April 2024

Introduction:
Right ventricular dysfunction and failure are independently associated with worse clinical outcomes, regardless of left ventricular EF. The molecular pathophysiology of right ventricular failure and its sex differences are poorly understood. The recent success of cGMP enhancing drugs in HF clinical trials indicated potential right heart benefits by activating cGMP signaling. However, details how myocardial cGMP signaling regulates right heart failure remain to be elucidated.

Hypothesis:
GC1α-cGMP signaling confers anti-remodeling benefits to RV with improvement of LV diastolic function after RV pressure overload.

Method:
Adult male and female constitutive GC1α knockout mice (GC1α KO) were subjected to pulmonary artery banding (PAB, 25G needle) and serial echocardiography were performed at 3- and 6-weeks post-surgery. Age and sex-matched wild type C57B6/J mice were used as controls.

Results:
Survival at 6wks post-PAB was worse in GC1αKO compared to WT controls (100 % of WT vs 38.5 % of GC1αKO, p<0.05; Gehan-Breslow-Wilcoxon-test) indicating the exacerbated heart failure by GC1α ablation. RV systolic function at 3 weeks post-surgery was deteriorated in GC1αKO male, assessed with RV FAC (%) (WT vs GC1αKO: 58.0 vs 35.6 p<0.05; t-test) and TAPSE (mm) (WT vs GC1αKO: 0.94 vs 0.64 p<0.05; t-test). Female showed limited RV systolic dysfunction and worse LV diastolic dysfunction at 3 weeks post-surgery compared to male, assessed with TAPSE (mm) (WT vs GC1αKO: 0.85 vs 0.63, p<0.05; t-test) and mitral IVS E/E’ (WT vs GC1αKO: 18.3 vs 29.3, p<0.05; t-test). Interestingly, the impact of GC1α ablation to RV systolic function is bigger in male, but that to LV diastolic function is bigger in female, indicating sex differences of GC1-cGMP regulated cardio-protective effects to right heart failure. The fetal gene expressions(
nppb
and
Myh7
) in right heart also showed worse right heart remodeling by GC1α ablation especially in male at 6 weeks post-surgery.

Conclusions:
Inactivation of GC1α-cGMP signaling induced right heart remodeling after PAB. Female mice showed LV diastolic dysfunction with limited right heart remodeling compared to age-matched male, indicating sex differences in GC1-cGMP related right heart protective mechanism.
Abstract 14308: Lamotrigine Inhibits the Inward Fast Sodium Current (I
Na
) in Epileptic Rat Cardiomyocytes
Authors: Contreras Vite Juan Antonio , Dumaine Robert
Published: April 2024

Introduction:
Lamotrigine (LTG) is widely prescribed to treat neurological disorders such as migraine, neurophatic pain, and epilepsy. Recently, LTG has been linked to Brugada síndrome (BrS) ECG associated with a reduction in sodium current (I
Na
) amplitude. Experimental studies have revealed that LTG blocks voltage gated sodium channels (VGSC).

Hypothesis:
Therefore, disrupting the depolarizing fast sodium inward current is a potential cause for arrhythmias. Recently our laboratory has shown that epilepsy induces molecular remodeling of the cardiac ventricle characterized by neuronal sodium channels overexpression, so it would be very plausible that LTG can cause important alterations on I
Na
in epileptic individuals.

Methods:
We used Patch-Clamp technique to test the effect of LTG on I
Na
in sham and epileptic rat ventricular cardiomyocytes.

Results:
We found that LTG inhibited I
Na
in a single dose-response manner with an IC
50
=326.35μM in sham rats. In epileptic rat cardiomyocytes the inhibitory effect was biphasic way with an IC
50
(1)=8.09 μM, which is close to the therapeutic range (between 12 and 50 μM), and a IC
50
(2)=333.66 μM. Moreover, LTG also altered sodium channels availability in biphasic manner with Vh(1)=-76.36 ± 0.31 mV and Vh(2)=-121.42 ± 1.38 mV, suggesting that LTG reduced the number of ion channels contributing to I
Na
.

Conclusions:
These findings may explain in part how LTG induce a Brugada pattern on the ECG of epileptic patients.
Abstract 14335: Abnormal Left Atrial Conduit Function in Obstructive Hypertrophic Cardiomyopathy is Mediated Through Elevated Left Ventricular Filling Pressure
Authors: Fohtung Raymond B , Mital Rohit , Lu Dai-yin , Ramsis Ramsis , Bibby Dwight , Schiller Nelson B , Beutner Katherine , Abraham Maria R , Abraham Theodore
Published: April 2024

Introduction:
Elevated left ventricular outflow tract (LVOT) gradient occurs in a majority of HCM patients and is associated with diastolic dysfunction, heart failure, atrial fibrillation and death. These adverse outcomes are also commonly associated with Left atrial (LA) dysfunction. Yet, the nature and extent of the relationship between LVOT gradient and LA function remains ill-understood.

Methods:
HCM patients were classified as obstructive (rest gradient ≥ 30 mmHg), labile (rest gradient < 30 mmHg, provoked gradient ≥ 30 mmHg) and non-obstructive (rest and provoked gradient < 30 mmHg). In addition to conventional analysis, LA reservoir, conduit and contractile strain were measured (TomTec Imaging Systems).

Results:
Of 135 patients, 34 (44% male) were obstructive, 36 (75% male) labile and 65 (63% male) non-obstructive HCM. Large LA volume index and elevated E/e’ was associated with elevated LVOT gradient at rest (r 0.17; p 0.04 and r 0.40; p<0.001, respectively) and with Valsalva (r 0.19; p 0.03 and r 0.33; p<0.001, respectively). Low LV strain was associated with elevated LVOT gradient with exercise (r -0.22, p 0.04). LA conduit strain (but not reservoir or contractile strain) was lower in patients with obstructive HCM compared to patients with non-obstructive HCM (13.1 ± 5.4 vs 11.0 ± 3.9%, p = 0.03, Figure 1). There was no significant difference in all LA strain parameters across all the other HCM types.

Conclusions:
Measures of elevated LV filling pressure (large LA volume index, elevated E/e’ and low LV strain) were associated with elevated LVOT gradient. LA conduit strain was lower in obstructive compared to non-obstructive HCM. Our data suggest that elevated LVOT gradient is associated with abnormal LA conduit function most likely mediated via elevated LV filling pressure.
Abstract 14339: Disparities in Transcatheter Mitral Valve Repair in Racial Minorities - From the National Inpatient Sample
Authors: Khan Muhammmad Zia , Khan Muhammad U , Zahid Salman , Ullah Waqas , balla Sudarshan
Published: April 2024

Introduction:
Racial disparities in cardiovascular diseases and interventions have been widely reported in previous studies, Whether the racial disparities exist with transcatheter mitral valve repair (TMVr) is largely unknown.

Hypothesis:
The purpose of this study is to assess racial disparities in the utilization and outcome of TMVr procedure in the United States using the National Inpatient Sample (NIS) database.

Methods:
We analyzed NIS data from January 2013 to December 2017 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes and International Classification of Diseases, 10th Revision, Clinical Modification ICD-10-CM codes. Multivariable analysis was done by using logistic regression model to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to determine variability in mortality, home discharges, vascular complications, cardiac complications, pulmonary complications, post op stroke and acute kidney injury by race.

Results:
A total of 13,410 weighted hospitalizations for TMVr procedure were included in our analysis. Multiple logistic regression analysis showed no significant difference in hospital mortality among the three racial groups. Pulmonary complications were more likely in the African American (adjusted Odds Ratio [aOR], 1.326[95% CI, 1.03-1.706], p-value= 0.03) and Hispanic population (aOR, 1.362[95% CI, 1.034-1.794], p-value= 0.03) (Figure).

Conclusions:
No significant difference in hospital mortality was noted among Caucasian, African American and Hispanic patients undergoing TMVr, however, we report a higher rate of post procedure respiratory complications in the minority races compared to Caucasian race.