bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16213: No Cardiac Benefit After Single Dose of Intramyocardial or Intravenous Mesenchymal Stem Cell-Derived Extracellular Vesicles Post-Myocardial Infarction Supports Need for Bioengineered Extracellular Vesicles With Non-Invasive Cardiac Uptake
Authors: Xu Cynthia M , Broadwin Mark , Faherty Patrick , Brinck Teixeira Rayane , Sellke Frank W , Abid Ruhul
Published: December 2023

Introduction:
In pre-clinical models, mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have benefits in ischemic CVD. We previously showed that only intramyocardial (IM) injection of MSC-EV, an invasive method of administration, and not intravenous (IV) injection, resulted in reliable cardiac uptake after acute MI. No prior studies have compared the functional outcome of IM versus IV injection after acute MI.

Hypothesis:
IM injection of MSC-EV will result in improved cardiac outcomes whereas IV injection will not.

Aim:
To demonstrate the long-term outcomes of IM versus IV MSC-EV after acute MI.

Methods:
MSC-EV were isolated and characterized. FVB mice underwent left anterior descending coronary artery ligation and subsequent injection of the following: 1) IM saline control (IM-C; n = 8), 2) IM 2*10
9
MSC-EV particles (IM-EV; n = 9), 3) IV saline control (IV-C; n = 8), and 4) IV 2*10
9
MSC-EV particles (IV-EV; n = 8). The mice underwent pre-operative, and post-operative weekly echocardiograms. On post-operative day 28, the mice were euthanized, and the hearts were harvested.

Results:
Preliminary data showed no significant differences in left ventricular ejection fraction (p = 0.6151) or fractional shortening (p = 0.1135) in the IM-EV and IV-EV groups compared to the controls IM-C and IV-C, respectively, at post-operative day 28 (Figure 1A). There were also no significant differences in infarct size (p = 0.05620) (Figure 1B) or anterior border zone fibrosis (p = 0.6333) (Figure 1C) on Masson-Trichrome staining.

Conclusions:
Preliminary findings demonstrate that a one-time IM or IV dose of MSC-EV given immediately after acute MI results in no observable effects. Additional MSC-EV doses after MI may produce beneficial effects. Results from our ongoing studies on the creation of stem cells bioengineered to produce MSC-EV with surface cardiac targeting peptides and immune-evasion properties will be presented in August 2023.
Abstract 16232: Life’s Essential 8 Cardiovascular Health Score and Cardiorespiratory Fitness in the Community
Authors: Ravichandran Sandhiya , Gajjar Priya , Walker Maura E , Shah Ravi , Xanthakis Vanessa , Lewis Gregory , Nayor Matthew G
Published: December 2023

Background:
Cardiorespiratory fitness (CRF) is a key indicator of cardiovascular health (CVH) and is inversely associated with cardiovascular disease (CVD) and mortality, but its relations with lifestyle behaviors and factors linked with CVH are incompletely elucidated.

Hypothesis:
Greater CVH, as assessed by a score comprising lifestyle and standard risk factors, is associated with greater CRF.

Aim:
To evaluate the cross-sectional relations of AHA’s Life’s Essential 8 (LE8) metrics with CRF in the community.

Methods:
Maximal cardiopulmonary exercise tests (CPET) were performed in the Framingham Heart Study (FHS). An LE8 score was constructed for each participant by averaging scores across all LE8 components (ranging 0-100). We related CRF and other CPET measures with total LE8 score, individual LE8 components as three-level variables (optimal/suboptimal/poor), and changes in LE8 score over an ≈8 year interval.

Results:
In 1838 FHS participants (age 54±9 years, 54% women, BMI 28±5 kg/m
2
), mean LE8 score was 76±12. In age- and sex-adjusted models, a higher LE8 score was associated with higher peak VO
2
, better ventilatory efficiency, lower resting heart rate, and favorable blood pressure response to exercise (p<0.0001 for all). A clinically meaningful 5-point higher LE8 score was associated with a 6.0% greater peak VO
2
(≈1.4 ml/kg/min at the sample mean). There was no evidence of effect modification by age, sex, or CVD status. The eight LE8 score components were statistically significantly associated with peak VO
2
in models adjusted for age and sex, but blood lipids, diet, and sleep health were no longer statistically significant after adjustment for all other LE8 components (
Figure
). Over an ≈8-year interval, a 5-unit increase in LE8 score was associated with a 3.7% higher peak VO
2
(p<0.0001).

Conclusion:
Higher LE8 score is associated with greater CRF in the community, highlighting the importance of CVH as assessed by LE8 metrics in maintaining and promoting CRF.
Abstract 16249: A Case of Myocarditis and Pneumonitis Associated With Pembrolizumab Therapy
Authors: Maragiri Sheetal R , Abdallah Wissam , Kemnic Tyler , Fermin David , Munoz Sherilyn , Koubek Richard , Franey Laura
Published: December 2023

Introduction:
Immune checkpoint inhibitors (ICI) are a novel therapy that activates antitumor immunity but can have varied immune-related adverse effects. As ICI therapy is used to treat malignancy, cases of autoimmune myocarditis and heart failure increase, thought to be due to PD-1 inhibition, which may be potentially fatal.

Case presentation:
A 37 yo female with history of autoimmune hepatitis and stage III melanoma on Pembrolizumab (ninth cycle 1.5 months prior) presented with chest pain, tachycardia, fatigue, dyspnea, and fever. Lab studies were notable for elevated troponin, lactic acidosis, and disseminated intravascular coagulation (DIC). CT thorax showed asymmetric ground glass opacities, concerning for ICI pneumonitis. Echocardiogram showed an LVEF of 15% with global hypokinesis. She was treated for severe sepsis, DIC, and respiratory failure, temporarily requiring intra-aortic balloon pump. Heart failure guideline-directed medical therapy (GDMT) was started. Clinical presentation was concerning for acute myocarditis related to ICI therapy as a cause for new cardiomyopathy. A cardiac MRI (CMR) revealed subepicardial late gadolinium enhancement (LGE) along the basal inferior/inferolateral wall segments concerning for myocarditis. Corticosteroids with a prolonged taper were started. Endomyocardial biopsy of the septum (EMB) was negative. Her clinical status improved and repeat echo showed LVEF recovery up to 45%.

Discussion:
Endomyocardial biopsy (EMB) provides definitive diagnosis of myocarditis and is recommended (Class I) for new-onset heart failure with hemodynamic compromise and/or arrhythmias. Although our patient’s EMB was negative (likely due to limitation of sample location), she met the 2013 ESC guideline diagnostic criteria for myocarditis with elevated troponin, functional and structural abnormalities on cardiac imaging.

With increased utilization of ICI therapy in the management of aggressive malignancies, it is important to monitor for potentially adverse effects such as autoimmune myocarditis. Standard treatment is prompt initiation of corticosteroids, though newer studies report successful treatment with immunomodulators, such as abatacept and ruxolitinib, if steroids are unsuccessful.
Abstract 16260: Children With Increased Native T1, Extracellular Volume and T2 Values on Initial Cardiac Magnetic Resonance Imaging for Acute Myocarditis Have Less Improvement in Late Gadolinium Enhancement on Follow Up Imaging: Risk Factor for Adverse Events?
Authors: Vaiyani Danish , Jones Andrea L , Harris Matthew A , Whitehead Kevin K , Biko David , Partington Sara , Restaino Kathryn , Lin Kimberly Y , Fogel Mark A
Published: December 2023

Introduction:
Late gadolinium enhancement (LGE) in pediatric patients with acute myocarditis has been shown to be a risk factor for adverse events. On follow up cardiac magnetic resonance imaging (CMR), some patients show improvement and/or resolution of LGE but others do not. Factors associated with residual LGE have not been described.

Hypothesis:
Measurements on initial CMR would be associated with degree of improvement of LGE on follow up CMR.

Methods:
We conducted a retrospective cohort study of patients <21 years with acute myocarditis who underwent initial CMR within 14 days of presentation and returned for follow up CMR. Those who suffered cardiac arrest or with autoimmune disease, known cardiomyopathy or congenital heart disease were excluded. LGE was defined as tissue with signal intensity 5 standard deviations above mean signal intensity of unaffected myocardium on viability imaging; this mass was measured and indexed to total left ventricular mass. Strain was measured using CMR feature tracking. Spearman’s correlation was used to determine associations between change in indexed LGE mass on follow up CMR to values from initial CMR.

Results:
We enrolled 36 patients aged 16.4 years (IQR 14.9-17.2 years) with median time to follow up CMR 229 days (IQR 171, 407). Native T1 (Figure 1), T2, peak T2 relaxation times and ECV on initial CMR inversely correlated with
change
in indexed LGE mass on follow up CMR while indexed right ventricular end diastolic volume (RVEDVi) on initial CMR positively correlated. (Table 1) Strain and ventricular function did not correlate with change in LGE mass on follow up CMR.

Conclusions:
Elevated T1 and T2 values and ECV on initial CMR in patients with acute myocarditis are associated with less improvement of LGE on follow up CMR; increased RVEDVi was associated with greater improvement. Further work is needed to determine which are the most useful predictors of residual LGE following myocarditis in children.
Abstract 16297: DPP-4 Inhibitor Sitagliptin Treatment Results in Altered Myocardial Metabolic Proteome and Oxidative Phosphorylation in a Swine Model of Chronic Myocardial Ischemia
Authors: Harris Dwight , Sabe Sharif A , Broadwin Mark , Bellam Krishna , Xu Cynthia , Li Janelle , Abid Ruhul , Sellke Frank W
Published: December 2023

Introduction:
Small animal models have shown increased cardiac function and decreased infarct size with DPP-4 inhibition, but many human studies have shown increased heart failure readmission or no benefits. We seek to bridge the gap from small animal models to humans by studying DPP-4 inhibitor sitagliptin in a swine model of chronic myocardial ischemia using proteomic analysis.

Methods:
Thirteen Yorkshire swine underwent placement of an ameroid constrictor on the left coronary circumflex artery to model chronic myocardial ischemia. Two weeks post-op, swine received either sitagliptin 100 mg daily (SIT, n=5) or no drug (CON, n=8). After five weeks of treatment, swine underwent functional measurements and tissue harvest. Myocardial tissue was sent for proteomic analysis or analyzed with immunoblot.

Results:
In the SIT group compared to CON, there was a strong trend towards decreased cardiac index (p=0.06), with decreased end-systolic and diastolic volumes (all p<0.05, Figure 1). Proteomics analysis identified 1,003 proteins in the non-ischemic and 728 proteins in the ischemic myocardium. The non-ischemic and ischemic myocardium had 396 and 166 significantly decreased proteins, respectively, in the SIT group compared to CON (all p<0.01). This included proteins involved in the citric acid cycle (TCA), fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS). Immunoblotting confirmed SIT was associated with decreased expression of several metabolic proteins including FAS, CPT1α, IDH1, and mitochondrial complexes I and II (all p<0.05).

Conclusions:
In a swine model of chronic myocardial ischemia, sitagliptin treatment resulted in a trend towards decreased cardiac index and decreased expression of proteins involved in OXPHOS, FAO, and the TCA in both ischemic and non-ischemic myocardium. These metabolic and functional changes may provide some mechanistic evidence for the increased heart failure readmission in clinical studies.
Abstract 16378: Adult Congenital Heart Disease Lesions Commonly Repaired at High-Quality Surgical Centers in Limited-Resource Settings Have Similar Outcomes as Pediatric Repairs
Authors: Wittenberg Rachel E , Gauvreau Kimberlee , Qi Liang , Caneo Luiz , sivalingam sivakumar , Jenkins Kathy J
Published: December 2023

Introduction:
Improved medical and surgical therapies have increased attention to congenital heart disease (CHD) across the lifespan. There are limited data on the global burden of adult CHD, which could guide treatment and program development in limited-resource settings.

Methods:
We analyzed all CHD surgeries from 2015-2020 at 33 programs in 16 countries, using audited data from the International Quality Improvement Collaborative for CHD. Demographic characteristics and outcomes (in-hospital mortality, major infection, and length of ICU stay) were compared for procedures with >100 cases in patients ≥18 years. Adult and pediatric CHD outcomes were compared.

Results:
Five procedures each contributed >100 cases, accounting for 56% of all adult CHD cases: atrial septal defect closure (ASD; 1061 cases), ventricular septal defect closure (VSD; 350 cases), tricuspid valvuloplasty (TV; 179 cases), tetralogy of Fallot repair (TOF; 141 cases), and pulmonary valve replacement (PVR; 118 cases). The distribution of adult CHD cases was relatively consistent from 2015-2020 (Figure 1A). Median age at surgery was 36 years (IQR 26-48) for ASD, 30 (23-41) for VSD, 39 (28-51) for TV, 26 (21-31) for TOF, and 23 (20-30) for PVR. Median BMI for TOF was 18.9 (IQR 16.7-21.4) compared to 21-22 for the other procedures. In-hospital mortality and major infection were higher for adult TOF (5.0% and 7.9%, respectively) and PVR (4.2%, 3.4%) compared to VSD (0.9%, 2.3%), TV (0.6%, 2.2%), and ASD (0.1%, 0.9%). Median duration of ICU stay was longer for TOF and PVR (77 and 72 hours, respectively) compared with the other procedures (41-48 hours). There was no significant difference in mortality or major infection between adult and pediatric patients for each procedure (Figure 1B).

Conclusions:
ASD, VSD, TOF, TV, and PVR are the most common adult CHD procedures at IQIC sites, accounting for over half of all adult cases. Adverse outcomes are low and similar among adult and pediatric patients.
Abstract 16410: Burden of Delirium on Mortality and Healthcare Resources Utilization in Geriatric Patients Hospitalized for Acute Coronary Syndrome: 5-years Retrospective Cohort Study
Authors: Al Ahmad Majd , Alhuneafat Laith , Al-Ahmad Anas , Hamza Mohammad , Satyavolu Bharadwaj , Waqar Hafiza Hareem , jabri ahmad , Al-Abdouh Ahmad , Alameh Anas
Published: December 2023

Introduction:
Acute coronary syndrome (ACS) and delirium are frequently observed in the geriatric population. Nevertheless, the precise impact of delirium on ACS outcomes and resource utilization remains inadequately elucidated.

Hypothesis:
We aim to investigate the burden of delirium on the outcomes of geriatric patients admitted for management of ACS.

Methods:
This is an analysis of the National Inpatient Sample of the years 2016 to 2020. We identified patients >= 65 years old who were admitted with a principal diagnosis of ACS. Outcome studied included mortality difference, and length of stay (LOS) and cost of care (COC) as indicatives of healthcare resources utilization. Regression analysis was performed to compare those that developed delirium vs. those that did not while adjusting for baseline characteristics and comorbidities

Results:
Out of 1,845,379 elderly patients admitted for ACS, 1.3% (24,090 patients) developed delirium. The delirium group did not experience higher rates of in-hospital mortality compared to the non-delirium group (aOR 1.022, p=0.69, 95% CI 0.916-1.140). However, elderly ACS patients with delirium had a longer length of stay (aMD 5.60 days, 95% CI 5.26-5.95, p<0.001) and higher cost of care (aMD $84,512, 95% CI $77,168-$91,857, p<0.001).

Conclusions:
Elderly patients hospitalized for ACS face extended hospital stays and higher costs of care when they develop delirium. These findings highlight the significant economic impact of delirium and emphasize the importance of preventive measures in elderly ACS patients
Abstract 16432: Screening for Cardiovascular Complications in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Hutchinson Zach , Smith Michael , Colglazier Elizabeth , Zinter Matt , Dvorak Christopher , Nawaytou Hythem
Published: December 2023

Introduction:
Hematopoietic stem cell transplantation (HSCT) carries a risk of cardiovascular morbidity, with reported incidences of pericardial effusion, pulmonary hypertension (PH), and reduced left ventricular ejection fraction (LVEF). Screening for cardiovascular complications in children undergoing HSCT may be essential, but its utility remains unexplored.

Hypothesis:
Screening HSCT children using echocardiography and brain natriuretic peptide (BNP) can detect cardiovascular complications associated with adverse outcomes in this population.

Methods:
This prospective single-center cohort study analyzed children undergoing HSCT over a 2-year period. Baseline, 7-day, and 30-day echocardiograms and BNP levels were obtained. Multilevel linear regression assessed changes in echocardiograms and BNP. Logistic regression determined associations between cardiac complications and outcomes.

Results:
The study included 43 patients, with a median age of 8.6 years (IQR 3.7, 14.6). Echocardiograms were obtained at baseline (n=43), day+7 (n=34), and day+30 (n=25). BNP levels were obtained at baseline (n=41), day+7 (n=34), and day+30 (n=12). Adverse outcomes included TMA (n=7), endothelial dysfunction (n=36), mechanical ventilation (n=8), and death (n=8). Pericardial effusion was the most common finding (n=2(6%) at day+7, n=4(16%) at day+30). Pericardial effusion at either day+7 or day+30 predicted death (OR 15.7, 95% CI 1.8-137, p=0.013) and TMA (OR 13.1, 95% CI 1.7-103, p=0.014). A 10% decrease in LVEF was observed in 6 (17%) of patients at day+7 and 2 (8%) at day+30, and was associated with reduced mortality (OR 0.1, 95% CI 0-0.6, p=0.009). The change in BNP level at day+7 was 7pg/mL (IQR 6, 66) and 5pg/mL (IQR 3, 20) at day+30. A 10 point increase in BNP carried an increased risk of endothelial dysfunction (OR 4.1, 95% CI 1.3-263, p<0.001). No patients developed PH.

Conclusions:
Cardiovascular complications are common after HSCT in children and carry diagnostic and prognostic significance. Further refinement of the screening protocol is necessary to determine the optimal timing of testing and assess its clinical utility.
Abstract 16438: Effect of Enzyme Replacement Therapy on Diastolic Function in Patients With Fabry Disease
Authors: Kim Minjeong , Seo Jiwon , Cho Iksung , Ha Jong-Won , Shim Chi Young Y , Hong Geu-Ru
Published: December 2023

Introduction:
The effects of ERT (enzyme replacement therapy) on cardiac manifestations in patients with Fabry disease (FD) are ambiguous. We aimed to investigate the response to ERT using diastolic stress echocardiography (DSE).

Hypothesis:
Diastolic function of FD would be improved after ERT.

Methods:
19 patients with FD who underwent ERT were analyzed. All patients had DSE prior to ERT and post ERT at 1 year follow-up. We measured early diastolic (e’) velocity of the mitral annulus at baseline, 25 Watt (W) and peak exercise. The difference of diastolic reserve (ΔDR) between pre and post ERT was calculated. Diastolic reserve is defined as the change of e’ from baseline to 25W or peak of exercise in DSE.

Results:
Overall diastolic reserve tends to be improved (ΔDR25W: 0.66±1.36, ΔDRpeak 1.47±2.61) after 1 year of the ERT. However, there was no significant change in left ventricular (LV) wall thickness and LV mass index before and after the ERT. When patients were classified into two groups according to ΔDRpeak (Group 1, n=6, ΔDRpeak ≤0; Group 2, n=13, ΔDRpeak >0), group 2 showed more higher pre-ERT MWE (93.6±3.2 vs 84.8±5.0, p<0.01). The pre-ERT longitudinal strain of LV was better in group 2 compared to group 1 (-14.6±2.6 vs -9.9±2.3m p<0.01). LAVI (44.0±12.9 vs 25.5±8.0, p<0.01), LVEDD (50.8±2.8 vs 46.5 ± 3.0, p<0.01) and LV mass index (204.5±57.5 vs 130.4±45.6, p=0.01) of pre ERT were higher in group 1.

Conclusions:
Diastolic function of FD was improved generally after ERT in FD patients FD patients who have relatively preserved chamber size and mechanical function before starting ERT showed a better response to ERT. In determining the ERT effect, evaluation of diastolic function is more useful than structural evaluation in patients with Fabry cardiomyopathy.
Abstract 16446: The Emergency or Non-Referral Admission Was Associated With the Poor Outcome in Adults Hospitalized for the Treatment of Severe Coronary Sequelae Following Kawasaki Disease: Analysis of the Nationwide Claim-Based Dataset From Japanese Registry of All Cardiac and Vascular Diseases- Diagnosis Procedure Combination
Authors: Mitani Yoshihide , Tsuda Etsuko , Tamura Toshihiro , Shiono Yasutsugu , Nakai Michikazu , Yokoi Hiroyoshi
Published: December 2023

Introduction:
Kawasaki disease (KD), first reported in 1967, is a risk for ischemic heart disease if complicated by coronary sequelae. However, limited information is available regarding the follow-up status and outcomes of adults hospitalized for severe coronary sequelae resulting from KD. Hypothesis: We hypothesize that emergency or non-referral admission is related to poor outcomes in adults with KD hospitalized for severe coronary sequelae.

Methods:
Using a nationwide claim-based dataset from Japan, we analyzed adult patients (aged 15 and above) with KD diagnosed according to ICD10 codes, who were hospitalized for the treatment of coronary artery sequelae between April 2013 and March 2020. Treatment groups included acute coronary syndrome (ACS), catheter intervention (PCI), coronary artery bypass grafting (CABG), or the heart failure/arrhythmia group (patients treated for heart failure or arrhythmia, excluding those in the other three groups). ACS was diagnosed based on ICD-10 codes, while other diagnoses were determined using specific procedures.

Results:
The study comprised 850 patients, predominantly male (74%), with a median age of 34 years (IQR:20-43) and a median body mass index of 22.5 (IQR:20.0-25.4). They were divided into four groups: ACS (n=112), PCI (n=86), CABG (n=92), and the heart failure/arrhythmia group (n=560). The overall patient cohort had emergency admissions (27%) and non-referral admissions (13%), as well as heart failure (46%) and arrhythmia treatment (84%). Outcome measures included intensive care unit care (24%), median hospitalization duration of 4 days (IQR:3-13), total hospital deaths (1%), and median direct medical fees (4932600 Japanese yen). A higher percentage of emergency or non-referral admissions in the ACS or the heart failure/arrhythmia group correlated with unfavorable outcome parameters (p<.05).

Conclusions:
The present nationwide claim-based dataset study of adults hospitalized for severe coronary sequelae following KD, characterized by young males with normal BMI, showed that emergency or non-referral admission is associated with poor outcomes in the ACS and heart failure/arrhythmia groups. These findings support the importance of healthcare transition for such patients with KD.
Abstract 16484: Utility of Steerable Sheaths and Intracardiac Echocardiography for Typical Atrial Flutter Ablation
Authors: Fry Levi , Deshmukh Amrish , Liang Jackson
Published: December 2023

Introduction:
Sheaths (SS) and intracardiac echocardiography (ICE) are being increasingly utilized to improve safety, efficacy, and efficiency of catheter ablation procedures for different arrhythmias. The utility of these tools to guide ablation of typical atrial flutter (AFL) are not well characterized.

Hypothesis:
The use of SS plus ICE during typical AFL ablation leads to improved procedural and long-term outcomes as well as shorter procedural, fluoroscopy, and total radiofrequency times.

Methods:
In this retrospective chart review, medical records were abstracted for patients undergoing typical AFL ablation alone between 7/2019-5/2023. Demographics, medical history, and baseline procedural data were collected. Procedural outcomes were achievement of bidirectional block and complications. Long term outcome was recurrence of typical AFL or unblocked cavotricuspid isthmus (CTI) at repeat ablation (for any arrhythmia). Data analyzed with intention-to-treat analysis.

Results:
197 patients were identified. The use of SS plus ICE had the shortest procedural time (69.81 ± 34.49 mins, p<0.001), total radiofrequency time (362.91 ± 502.62 secs, p=0.005), and fluoroscopy time (5.28 ± 3.34 mins, p<0.001) (Figure 1). When patients were divided based on SS alone, both procedural and radiofrequency times were shorter with the use of SS vs no SS (81.04 ± 40.37 vs 91.74 ± 37.67 mins, p<0.001; 370.02 ± 460.44 vs 602.27 ± 592.28 secs, p=0.001), however, fluoroscopy time was longer (8.25 ± 7.75 vs 6.60 ± 5.58 mins, p<0.001). There was no difference between acute procedural success rates. Those in SS group were less likely to have recurrent typical AFL or unblocked CTI on redo ablation (0 out of 49 [0%] vs 6 out of 148 [4%]).

Conclusion:
Typical AFL ablation using SS plus ICE resulted in shorter procedural, total radiofrequency, and fluoroscopy times with similar acute procedural success rates. The use of SS (regardless of ICE) is associated with increased long-term success rate.
Abstract 16485: Treatment With PCSK9 Inhibitors Influence miRNAs Expression and Changes of Arterial Wall Properties
Authors: Rehberger Likozar Andreja , Ugovšek Sabina , Levstek Tina , Trebušak Podkrajšek Katarina , SEBESTJEN Miran
Published: December 2023

Background and aim:
MicroRNAs (miRNAs) are involved in the synthesis of proprotein convertase subtilisin-kexin type 9(PCSK9), which is one of regulators of low-density lipoprotein cholesterol (LDL-C) metabolism. There is no data on whether changes in the expression of miRNAs involved in PCSK9 metabolism, could be related to arterial wall properties changes. The aim was to verify whether PCSK9 inhibitors (PCSK9i) treatment and the changes in the expression of miRNAs are associated with arterial wall properties in post-myocardial infarction (MI) patients with insufficiently regulated LDL-C levels and increased Lp(a) levels.

Methods:
Seventy-six participants after MI were enrolled and randomized to a placebo group or PCSK9i group. The treatment group received subcutaneous alirocumab 150 mg or evolokumab 140 mg, every 2 weeks. Blood for biochemical and genetic analysis was taken and ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed. All measurements were measured initially and after 6 months of treatment.

Results:
FMD improved from 10.9±6.3 to 14.4±5.7% in the PCSK9i group and 10.8±6.8 to 11.2±4.6% in the placebo group (p<0.001, p=0.584). PWV changed from 5.8±1.4 to 5.5±1.6 m/s (p=0.024) in the PCSK9i group and in the placebo group from 5.6±1.5 to 5.5±1.1 m/s (p=0.879), with better improvement in the treated group (p=0.007). c-IMT decreased in the PCSK9i group (from 0.65±0.10 to 0.63±0.10 mm; p=0.017), with no change in the placebo group (from 0.64±0.09 to 0.63±0.09 mm; p=0.482). The expression of miR-191-5p and miR-483-5p increased in the PCSK9i group (p=0.028, p=0.020; respectively). The expression of miR-191-5p significantly decreased in the placebo group (p< 0.001). A decrease in c-IMT was associated with a decrease in the expression of miR-224-5p (r=0.303; p=0.019), miR-337-3p (r=0.329; p=0.010) and miR-483-5p (r=0.367; p=0.004).

Conclusions:
Our results suggest that changes in selected miRNAs were associated with changes in the morphological properties of the arterial vessel wall. We have shown that the increase in miR-483-5p expression can be a good indicator of the regression of morphological atherosclerotic changes.
Abstract 16508: Use of Ultrasound Enhancing Agents in Echocardiography for Stroke Across Yale New Haven Health System
Authors: Jeyashanmugaraja Gini Priyadharshini , Alam Md Mashiul , McNamara Robert L , Shkolnik Evgeny
Published: December 2023

Background:
Transthoracic echocardiography (TTE) is routinely performed for evaluation of stroke. We examined patterns of ultrasound enhancing agent (UEA) use for stroke across Yale New Haven Health System (YNHHS) Hypothesis: Prevalence of left ventricular (LV) thrombus depends on LV function, wall motion and UEA use.

Methods:
15209 TTE studies with indication of cerebrovascular accident or transient ischemic attack were performed from January 2019 to December 2022 across YNHHS. UEA was used in 7578 studies (49.8%). We compared the prevalence of LV thrombus and frequency of UEA use stratified by location (community hospitals, university hospitals, and outpatient sites) and by LV function. Chi square was used to compare rates of LV thrombus as well as frequency of UEA use stratified by LV function and location.

Results:
UEA use varied from 2.6% in community outpatient sites, 23.3 % in community hospitals to 77% in a university hospital. LV thrombus was detected in 56 of 7578 UEA studies (0.74%). Increasing prevalence of LV thrombus was associated with decreasing LV function (p<0.0001). LV thrombus was detected only in 1/3716 UEA studies (0.027%) with normal LV function and normal wall motion. Increased frequency of contrast use in university hospital compared with community hospitals did not lead to overall higher rate of thrombus detection.When stratified by LV function, only subgroup with normal function had marginally higher rate of LV thrombus, but prevalence of LV thrombus in this subgroup was very low.

Conclusion:
Significant variability of UEA in TTE exists for evaluation of stroke across YNHHS with low prevalence of thrombus in hyperdynamic to normal LV function without wall motion abnormalities. Increased use of UEA was not associated with increased rate of LV thrombus detection, except group with normal function. Value of increased detection in this group with low prevalence of thrombus should be balanced against cost and risk of adverse reactions.
Abstract 16546: Impact of Hyperuricemia on 5-year Clinical Outcomes in Patients With Percutaneous Transluminal Angioplasty
Authors: Rha Seung-Woon , Ahn Woo Jin , An Seong Joon , Choi Byoung Geol , Choi Se Yeon , Byun Jae Kyeong , Cha Jinah , Hyun Sujin , Park Soohyung , Kang Dong Oh O , Park Eun Jin J , Choi Cheol Ung
Published: December 2023

Background:
Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA).

Methods:
A total of 943 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N=168) and the normal group (N=550). Hyperuricemia was defined as a uric acid level ≥7.0 mg/dL in men, and ≥6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). In addition, inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders.

Results:
After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with MACCE but associated with an increased incidence of MI (2.6% vs. 0.5%, p = 0.001), and coronary revascularization (6.7% vs. 3.9%, p = 0.018). Also, the hyperuricemia group was associated with higher incidence of MALE (45.3% vs. 28.9%, p < 0.001), including a target extremity revascularization (TER; 25.1% vs. 15.9%, p < 0.001), non-TER (11.5% vs. 5.6%, p < 0.001), and TES (22.8% vs. 16.2%, p = 0.002).

Conclusions:
In the present study, hyperuricemia was associated with worse clinical outcomes during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes.
Abstract 16553: Effects of Digital Yoga on Physical and Psychological Outcomes in Patients With Heart Failure: A Randomised Controlled Trial
Authors: Stromberg Anna , Klompstra Leonie , Papageorgiou Joanna-Maria , Hedbom Towe , Lundberg Marie , Orwelius Lotti , Thylen Ingela , Jaarsma Tiny
Published: December 2023

Objectives:
To determine effects of digitally delivered yoga on exercise capacity and patient-reported outcome measures.

Methods:
Two-arm randomised controlled study including participants with heart failure or conditions in need of intensive care from four hospitals in Sweden. Participants were randomised to a control group receiving individual exercise advice or to the intervention group (tele-yoga). The intervention lasted for 3 months and included live-streamed group-yoga via Zoom for 60 minutes twice/week and individual yoga for a minimum of 10 minutes/day using an app. The primary endpoint of the study was a combined endpoint consisting of change in functional capacity measured by 6 minute walk test (6MWT), health-related quality of life (EQ-5D index/VAS) and symptoms of anxiety and depression (hospital anxiety and depression scale - HADS). The primary end-point analysis after 3 months follow-up compared the change in the combined endpoint between the participants in the tele-yoga and control group. Secondary endpoints included separate analysis of functional capacity, health-related quality of life and symptoms of anxiety/depression.

Results:
311 participants were randomized to tele-yoga (n=156) and control (n=155), mean age 66 years, 30% women, 80% diagnosed with heart failure. There was a significant improvement in favor of the tele-yoga group in the combined primary endpoint consisting of physical function, quality of life and anxiety and depression (p=.006). When analysing them separately, there was a significant improvement in 6MWT (p=.008) and quality of life in EQ-5D VAS (p=.014), but not in EQ-5D index (p=.12), and a significant difference between the groups in symptoms of anxiety and depression (p=.03). Median attendance to yoga-sessions was 20 sessions (maximum 24) and 69% of the study participants were adherent to >18 tele-yoga sessions. There were no adverse events reported during yoga sessions or app usage.

Conclusion:
Digitally delivered mind-body training such as tele-yoga showed a significant improvement in the combined end-point consisting of physical function, health-related quality of life and mental health. Tele-yoga may be a promising new form of rehabilitation for patients with heart failure.
Abstract 16584: Spleen Tyrosine Kinase Inhibition Interferes With Platelet NLRP3 Inflammasome Activation in Sickle Cell Mice Leading to Reduced Platelet Aggregation
Authors: Vogel Sebastian , Kamimura Sayuri , Smith Meghann , Almeida Luis , Strich Jeffrey , Quezado Zena
Published: December 2023

Introduction:
The NOD-like receptor protein 3 (NLRP3) inflammasome is a critical inflammatory mechanism that has recently been found to be upregulated in platelets in sickle cell disease (SCD). Fostamatinib is a prodrug of the Spleen Tyrosine Kinase (Syk) inhibitor R406 that targets platelets and is approved for the treatment of immune thrombocytopenia. The effect of Syk inhibition on platelet NLRP3 inflammasome activation in SCD is unexplored.

Methods:
We used a SCD mouse model, the Townes strain, which expresses human sickle hemoglobin. NLRP3 inflammasome activation was assessed in isolated platelets with fluorescent labeled inhibitor of caspase-1 (FLICA) assay and immunofluorescence staining of intraplatelet NLRP3 and the adaptor apoptosis-associated speck-like protein containing a CARD (ASC) coupled with confocal laser scanning microscopy. Platelet aggregation and ATP secretion were studied with whole blood impedance aggregometry and luminescence. Isolated platelets or blood samples were treated with the Syk inhibitor R406 and/or the NLRP3 activator nigericin where indicated. Collagen was used as platelet agonist.

Results:
R406 markedly decreased platelet caspase-1 activation and NLRP3:ASC speck formation found in platelets from SCD mice (RFUs: 228 ± 25.3 vs. 450.2 ± 63, mean ± SD, R406 vs. vehicle, p<0.001). R406 had no effect in platelets from control mice, where only low levels of caspase-1 activity and NLRP3:ASC specks were detected in platelets. Platelet aggregation and ATP secretion were elevated in SCD mice, which was abrogated by R406 (AUC: aggregation, 39 ± 2.6 vs. 65.8 ± 4.7, mean ± SD, R406 vs. vehicle, p<0.001; ATP, 7.2 ± 1.5 vs. 13.9 ± 1.6, mean ± SD, R406 vs. vehicle, p<0.001). Strikingly, the NLRP3 activator nigericin reversed the inhibitory effect of R406 on platelet aggregation (44 ± 11.5% increase, p<0.001) and ATP secretion (48.9 ± 22% increase, p<0.01) in SCD mice, suggesting a functionally active link in platelets between Syk and NLRP3.

Conclusion:
Syk inhibition with R406 impairs NLRP3 inflammasome activation in platelets from SCD mice and interferes with platelet aggregation and ATP secretion in an NLRP3-dependent manner. Targeting Syk and NLRP3 in platelets might be a useful therapeutic approach in SCD.
Abstract 16590: Left Ventricular Remodelling Following Transcatheter Mitral Valve Replacement With the Innovalve System
Authors: Goitein Orly , Meerkin David , Guetta Victor , Schwammenthal Ehud , BUTNARU ADI , Avner Avi , Rihal Charanjit , Raanani Ehud
Published: December 2023

Introduction:
Transcatheter Mitral Valve Replacement (TMVR) using a trans-septal approach is a new therapeutic option for patients with severe mitral regurgitation (MR). However, both surgical as well as currently under-testing trans-catheter approach, are shown to cause decrease in LV function. The Innovalve TMVR is a novel self-expandable transcatheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intravalvular posterior position after subvalvular anchoring by rotation of 6 circumferential arms

Hypothesis:
TMVR procedure (Innovalve system) leads to LV anatomical and functional changes

Methods:
CT was performed before the Innovalve TMVR procedure, and after 3 to 6 months. CT protocol included retrospective ECG gating with full cardiac cycle coverage. LV end diastolic and end systolic diameters (LVEDD, LVESD) were measured in the left ventricular outflow tract orientation at the most basal level. Tip to tip papillary muscle distance was measured in the short axis orientation at the most basal slice demonstrating the papillary muscle tips. LV ejection fraction (LVEF) was calculated using the end systolic and end diastolic volumes. All measurements were performed at end systole and end diastole before MTVR and after 3-6 months using a dedicated platform (3Mensio).

Results:
Ten patients (7 males) average age 69+/-10 years, underwent the Innovalve TMVR procedure. Average LVESD decreased from 52±15 mm at baseline to 44±15mm (P=0.016) at 3-6 months. Similarly, LVEDD decreased from 60±14 mm at baseline, to 52±13mm at 3-6 months (P=0.039). Average papillary muscle tip to tip distance at end diastole (ED) decreased from 31.7±7mm at baseline to 28.4±6.5mm at 3-6 months (P=0.047).A trend of LVEF improvement was evident with an increase from 35%±12 average at baseline compared with 39%±12 average after 3-6 months (P=0.346).

Conclusions:
These preliminary results show that the TMVR procedure using the Innovalve system may result in favourable LV reverse remodelling changes including reduction of LVESD, LVEDD and ED papillary muscle distances, with improved LVEF. This encouraging data might suggest favourable postprocedural structural LV change.
Abstract 16592: Cancer as a New Risk Factor for Major Adverse Cardiovascular Events in Secondary Prevention
Authors: Melchiori Renzo , Diaz Saravia Sara , Szlaien Lucas , Rubio Pablo , Baratta Sergio , Hita Alejandro , Mouriño Romina , Rizzo Manglio M
Published: December 2023

Introduction:
The inflammatory mechanisms of cancer can be associated to the formation and progression of atherosclerosis. There is scarce evidence about the evolution of oncologic patients in secondary prevention after an Acute Coronary Syndrome (ACS).

Methods:
An observational retrospective study was done with 937 patients who underwent a PCI for Acute Coronary Syndrome (ACS) from 2008 to 2022. Patients with a prior history or Major Cardiovascular Events (MACE) were excluded, leaving a total of 787 patients. They were then divided into two subgroups according to the presence or absence of cancer: G1 non-oncologic, and G2 oncologic. The primary endpoint was a composite of MACE in secondary prevention within 3 years of STEMI.

Results:
G1 group consisted of 698 patients, and G2 of 89 patients. A total of 180 (22.9%) MACE were identified in the follow-up period in both groups combined, with a median follow-up time of 45 months [IQR= 14-72]. The cumulative incidence of MACE for G1 was 22.2% (155/698) and 28.4% (25/88) for G2. The median follow-up time for G1 was 48 months (IQR=15-84), and for G2 was 36 months (IQR=11-48). G2 presented a density index of MACE significantly superior compared to G1 (0.78 MACE/100 patients/month CI 95% [0.51-1.12] vs 0.48 MACE/100 patients/month CI 95% [0.37-0.50], p 0.01). Kaplan-Meier analysis showed a significantly higher probability of MACE in G2 compared to G1 (P = 0.0086). Multivariable Cox Hazard analysis showed that a history of cancer was an independent and significant predictor of MACE (HR 1.66, 95% CI [1.1-2.6], P = 0.025) adjusted for other risk factors (hypertension, diabetes, smoking history, sedentarism, obesity, age, sex, and family history).

Conclusions:
In our population, patients with cancer (G2) had a higher incidence of MACE during follow-up. History of cancer behaved as a significant and independent risk factor for MACE adjusted for other classical risk factors. Further studies are warranted to investigate this phenomenon.
Abstract 16593: The DEAD-Box RNA Helicase Ddx41 Contributes to Adverse Cardiac Remodeling During Pressure Overload Through Modulation of RNA Metabolism
Authors: Liu Wenhao , Higashikuni Yasutomi , Obana Takumi , Tanaka Yu , Hirata Yoichiro , Sata Masataka
Published: December 2023

Introduction:
RNA metabolism represents an essential biochemical process that governs protein biosynthesis, an operation that is modulated by RNA-binding proteins. Although shifts in RNA metabolism have been implicated in the pathogenesis of heart failure, the role of RNA-binding proteins in the heart remains largely unknown.

Methods:
Whole-genome CRISPRi screening was performed in HL-1 cardiomyocyte cell line transduced with dCAS9-KRAB. Phenylephrine, cobalt chloride and hydrogen peroxide were used as pathological stressors. Neonatal rat ventricular myocytes (NRVMs) were used for further in vitro experiments. DNA damage and mitochondrial function were assessed by phospho-H2AX detection and mitochondrial membrane potential assay, respectively. Transcriptome was assessed in NRVMs treated with Ddx41 or control siRNA. RNA Immunoprecipitation sequencing (RIP-seq) was performed by using NRVMs overexpressing FLAG-tag-labelled Ddx41. 8- to 12-week old wild-type and transgenic mice with cardiomyocyte-specific overexpression of Ddx41 were used for animal experiments. Pressure overload was induced by transverse aortic constriction (TAC). Cardiac phenotype was assessed by echocardiographic and histological analyses.

Results:
CRISPRi screening and validation experiment identified Ddx41, a DEAD-box RNA helicase, as one of molecules whose inhibition protects HL-1 cardiomyocytes against various pathological stressors. Knockdown of Ddx41 showed protective effect in NRVMs against doxorubicin stress with improvement of DNA damage, whereas overexpression of Ddx41 induced mitochondrial dysfunction. Transcriptome analysis using NRVMs demonstrated that Ddx41 knockdown alters expression levels of genes related to cardiac hypertrophy, energy metabolism, extracellular matrix formation and wound healing. RIP-seq analysis revealed that Ddx41 binds to mRNAs of genes related to inflammatory responses. Ddx41-Tg mice showed higher mortality and exacerbated adverse cardiac remodeling after TAC, compared with wild-type mice.

Conclusions:
Our results suggest that Ddx41 contributes to adverse cardiac remodeling during pressure overload through modulation of RNA metabolism. Ddx41 might be a novel therapeutic target for heart failure.
Abstract 16599: Deep Learning Prediction of Cardiac Chamber Enlargement on Chest Radiographs
Authors: Davila David M , Barnawi Rashid , Masoudi Samira , Mahmoodi Amin , Hsiao Albert , Hahn Lewis
Published: December 2023

Background:
Chest radiographs (CXRs) are the most commonly performed radiographic exam. The heart is routinely assessed on frontal CXRs using the cardiothoracic ratio (CTR) to identify cardiomegaly, but the predictive performance of CTR is limited by variability in patient position, lung volumes, and radiographic technique. Thus, CXR may miss a substantial proportion of patients with cardiac disease.

Hypothesis:
A deep learning (DL) algorithm can accurately identify cardiac chamber enlargement on CXRs and exceed the predictive performance of cardiothoracic ratio.

Methods:
Frontal CXRs (n=6,228 cases from unique patients, single-site, dated 2014-2022), obtained on the same day as transthoracic echocardiography (reference standard for cardiac chamber enlargement), were randomly grouped for DL model training (n=4,969), validation (n=627), and testing (n=634). A pre-trained EfficientNet-B6 convolutional neural network was modified to predict the presence of one or more enlarged cardiac chambers. The DL model's performance was benchmarked against manual CTR measurements by two radiologists on a random subset of 150 anteroposterior CXRs from the test set.

Results:
The DL model demonstrated an AUROC (Area under the Receiver Operating Characteristic curve) of 0.78 in the validation set and an AUROC of 0.79 in the unseen test set. The model achieved 73% accuracy, 77% sensitivity, and 67% specificity on the validation set and showed similar results on the test set with 72% accuracy, 77% sensitivity, and 64% specificity. The model outperformed manual CTR measurements for identification of chamber enlargement on the random subset of test set CXRs (AUROC of 0.85 vs. 0.75; p < 0.006, Figure 1).

Conclusion:
The DL model significantly outperformed traditional CTR assessment for cardiac chamber enlargement on CXR. DL models may improve radiologist identification of cardiac disease on CXR and prompt formal cardiac evaluation.