bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15216: Right Ventricular Dysfunction Predictors and Prognostic Value in Ischemic and Non-Ischemic Cardiomyopathies: A Cardiac Magnetic Resonance Study
Authors: Wang Tom Kai Ming K , Kocyigit Duygu , Chan Nicholas , Bullen Jennifer , Popovic Zoran B , Tang Wai Hong W , Griffin Brian P , Flamm Scott D , Kwon Deborah H
Published: June 2023

Background:
Cardiac magnetic resonance imaging (CMR) is the reference standard for right ventricle (RV) quantification, however predictors and prognosis of RV dysfunction in cardiomyopathy patients, including differences between ischemic (ICM) and non-ischemic (NICM) cardiomyopathies, remain not well understood. We evaluated the factors and outcomes associated with CMR-derived reduced RV systolic function, and compared by type of cardiomyopathy.

Methods:
Adult cardiomyopathy patients undergoing CMR with RV quantified during 2002-2017 were retrospectively studied. Multivariable linear and Cox regression were used to identify factors associated with reduced RV ejection fraction (RVEF) and the primary endpoint (all-cause death, heart transplant or LVAD) during follow-up.

Results:
Amongst 771 ICM and 624 NICM patients (mean ages 62.3±11.2 and 52.8±15.9 years, 190 (24.6%) and 253 (40.5%) were female respectively), mean RVEFs were 43±14% and 43±13% respectively. The primary endpoint occurred in 455 (59.0%) ICM and 113 (18.1%) NICM patients over mean follow-up of 5.3±4.5 years. Predictors of lower RVEF in ICM were younger age, lower eGFR, lower left ventricular ejection fraction, higher right ventricular end-diastolic volume indexed and higher mitral regurgitant fraction; and in NICM were male sex, NYHA class III-IV, right bundle branch block, lower left ventricular ejection fraction, higher right ventricular end-diastolic volume and higher mitral regurgitation fraction. Reduced RVEF was associated with the primary endpoint in univariable analysis in both ICM and NICM, but only remained so for NICM in multivariable analysis of the primary endpoint as shown in the table.

Conclusion:
Reduced RVEF is associated with adverse prognosis, however was only independently associated with the primary endpoint in NCIM but not ICM. Key predictors of RV dysfunction in both ICM and NICM were identified, with some similar and some different predictors between them.
Abstract 15228: Manganese-Enhanced MRI (MEMRI) Determines the Mechanistic Efficacy of Exosome Therapy in a Porcine Myocardial Infarction Model
Authors: Takashima Hiroyuki , Ikeda Gentaro , Zhao Chunli , Bayardo Nathan , O'Brien Connor , Yang Phillip C
Published: June 2023

Introduction:
Transplantation of exosomes from mesenchymal stem cells (MSCs) and induced pluripotent stem cell derived cardiomyocytes (iCMs) improves heart function after myocardial infarction (MI). However, imaging methods have not been established to assess the mechanism of these treatments. Contrast imaging with gadolinium delayed-enhancement MRI (DEMRI) allows non-specific quantification of myocardial fibrosis. In contrast, MEMRI demonstrates active uptake of manganese into intracellular space by the viable cardiomyocytes via L-type calcium channel. MEMRI delineates the level of cellular metabolism and identifies the recovery of the injured but viable cardiomyocytes in the peri-infarct region (PIR).

Hypothesis:
MEMRI reflects the mechanistic efficacy of cell therapy.

Methods:
Yorkshire swine were subject to percutaneous proximal left anterior descending artery occlusion for 1 hour. Ten 500ul injections containing 5 x 10
11
exosomes isolated from MSCs and iCMs were delivered transendocardially to the PIR. Four weeks after injury, left ventricular ejection fraction (LVEF), and myocardial scar/viability were measured. DEMRI and MEMRI delineated the PIR to quantify the effects of exosomes.

Results:
The LVEF of PBS (control), MSC-exosome, and iCM-exosome groups was 18.66% ± 4.23, 27.46% ± 6.16, and 29.5% ± 3.96*, respectively (*p<0.05). The % contrast enhancement by DEMRI over total LV volume were 29.38% ± 4.86, 28.76% ± 5.02, and 29.58% ± 5.55, respectively. Meanwhile, the % contrast nulling (CN, non-viable) by MEMRI were 20.51% ± 3.86, 9.53% ± 1.99, and 7.31% ± 2.62*, respectively (*p<0.01). mRNA seq of the porcine myocardium and subsequent gene ontology and KEGG analyses demonstrated significant differential gene expression of iCM-exosome group related to calcium regulation (adenylate cyclase 7, 3.30-fold change) and sarcoplasmic reticulum calcium ion transport (chemokine receptor 5, 3.15-fold change).

Conclusions:
The % CN reduction of MEMRI reflects improved cardiomyocyte metabolism and calcium handing by exosome therapy. The underlying mechanism and functional improvement are identified by MEMRI.
Abstract 15241: Mixed Meal Tolerance Test Elicits Distinct Metabolite Kinetics for Individuals With and Without Diabetes
Authors: Mi Michael Y , Whitlock Mark , shi xu , Farrell Laurie A , Bhambhani Victoria M , Quadir Juweria , Blatnik Matthew , Wald Kyle P , Tierney Brendan , Kim Albert , loudon peter , Chen Zsu-Zsu , Roth Flach Rachel J , Gerszten Robert E
Published: June 2023

Introduction:
Branched chain amino acids (BCAA) are strongly associated with incident diabetes and CVD, and drugs that target their metabolism, especially in the context of a meal, are emerging treatments for diabetes given supportive genetic data. However, little is known about how BCAA, their breakdown metabolites—branched chain ketoacids (BCKA), and other metabolites change after a meal.

Hypothesis:
BCAA and BCKA levels are higher in individuals with diabetes after a mixed meal tolerance test (MMTT) than in those without diabetes, and a MMTT will uncover additional metabolites involved in dysregulated metabolic pathways secondary to diabetes.

Methods:
We administered a MMTT to 13 adults with diabetes treated by metformin alone and 11 age and sex matched controls. We measured BCKA, BCAA, and 194 metabolites at 8 timepoints across 6 hours. We used a mixed model for repeated measurements to compare between group differences at each timepoint with adjustment for baseline levels.

Results:
Across the participants (57 ± 8 years, 71% female, BMI 28 ± 4 kg/m
2
), adjusted BCAA levels were similar at all timepoints between groups, but adjusted BCKA levels were higher in those with diabetes at 120 minutes (Figure). An additional 9 metabolites had 4 or more timepoints with significant between group differences (Figure). Acylcarnitine, palmitic acid, and linoleic acid showed slower rates of decrease and recovery in those with diabetes, altogether supportive of impaired fatty acid uptake and oxidation. Glycocholic acid showed no increase in those with diabetes, a finding that requires further study given growing recognition of bile acids’ paracrine effects on the liver.

Conclusions:
In contrast to BCAA, BCKA remained elevated after a MMTT in those with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the link between BCAA and diabetes. Other metabolites with different kinetics after a MMTT may be markers of dysmetabolism and impaired nutrient handling.
Abstract 15243: Incidence and Predictors of Chemotherapy-Induced Cardiomyopathy in African Americans: A Single-Center Experience
Authors: Abduljabar Hamzah N , Grewal Udhayvir S , Babbili Akhilesh , Andrus Victoria , Dhaliwal Lovekirat S , Dominic Paari
Published: June 2023

Introduction:
African Americans (AA) have largely been under-represented in randomized clinical trials investigating chemotherapy-induced cardiomyopathy (CICM) associated with doxorubicin and trastuzumab. Limited and conflicting evidence has linked higher incidence of CICM among AA patients to a higher prevalence of underlying co-morbidities.

Hypothesis:
African Americans have a higher incidence of CICM which is associated with higher prevalence of underlying co-morbidities in these patients.

Methods:
We retrospectively identified and included AA patients who underwent treatment with doxorubicin and trastuzumab at our institution. CICM was defined as a decline in ejection fraction (EF) to <50% OR >/=10% decline in baseline EF post-treatment. A univariate analysis was performed to study the association of common co-morbidities with CICM. JMP software (SAS v 9.4) was used for statistical analysis.

Results:
A total of 121 patients were included for analysis, out of which, 52.1% (63/121) and 47.9% (58/121) were treated with trastuzumab and doxorubicin respectively. Majority (85.1%, 103/121) were females and the mean age was 62.4±5.2 years. Median EF pre- and post-treatment were 65% (IQR 60%,65%) and 60% (IQR 55%,65%) respectively. The cumulative incidence of CICM in our cohort was 24% (29/121). There was no statistically significant association of CICM with female sex [OR=0.79 (0.25-2.99), p=0.68], age [OR=0.99 (0.96-1.02), p=0.88], pre-treatment EF [OR=1.09 (0.96-1.94), p=0.27], hypertension [OR=1.27 (0.51-3.18), p=0.60], diabetes [OR=1.91 (0.89-4.95), p=0.13], hyperlipidemia [OR=1.19 (0.44-2.92), p=0.78] or coronary artery disease [OR=1.93 (0.68-5.93), p=0.21].

Conclusions:
Per existing literature, the incidence of CICM in our cohort of AA patients is higher than general population. As historically postulated, CICM was not found to be associated with pre-existing co-morbidities. Further clinical and translational research is needed to study genetic and pathophysiological mechanisms driving CICM in AA patients.
Abstract 15258: An Unobvious Benefit of the Coexistence of Arterial Hypertension and Atrial Fibrillation - Results of Nationwide Cross-Sectional Study From Central and Eastern Europe
Authors: Zieleniewicz Piotr , Kalarus Zbigniew , Opolski Grzegorz , Sredniawa Beata , Stokwiszewski Jakub , Wierucki Lukasz , Kazimierczak Jaroslaw , Grodzicki Tomasz , Zdrojewski Tomasz
Published: June 2023

Introduction:
Poland represents the region of Central and Eastern Europe with high cardiovascular risk and a rapidly aging population with an ever-increasing prevalence of arterial hypertension (AH) and atrial fibrillation (AF). Our study describes the epidemiology of these conditions and factors associated with AF in the elderly.

Methods:
In a representative sample of 3014 Poles aged 65 years and over (mean age 77.5 years old, 49.1% women) questionnaire data, blood pressure measurements and blood samples were taken. Hypertension was defined as mean SBP ≥140mmHg or DBP ≥90mmHg or treatment of hypertension. Each patient was screened for AF by continuous ECG monitoring for up to 30 days using a validated ECG vest.

Results:
Overall prevalence of AH was 80.9% and overall prevalence of AF was 19.2%. Both conditions coexisted in 16.7% of participants and AF with no AH was observed in only 2.5% of participants. Hypertension was significantly more common in patients with AF than in these without AF (87.1% vs 79.4%, p<0.05). Mean systolic blood pressure and pulse pressure were significantly lower in the AF population (139.7 mmHg vs 142.6 mmHg, p<0.05, 61.3 mmHg vs 63.9 mmHg, p<0.05 respectively). In hypertensive patients the AF was more often paroxysmal than persistent/permanent (11.9% vs 8.8%, p<0.05), but the episodes of paroxysmal AF lasted longer than in patients without AH (14.9 hours vs 7.6 hours in men, p<0.05; 11.2 hours vs 3.5 hours in women, p<0.05). Participants with coexisting AF and AH were more often aware of both AF (79.9% vs 69.2%, p<0.05) and AH (88.9% vs 84.1%, p<0.05). Significant factors associated with AF occurrence in hypertensive patients were heart failure (OR 2.91), male gender (OR 1.94), elevated NT-proBNP level (OR 1.73), diabetes (OR 1.44), hyperthyroidism (OR 1.44), obesity (OR 1.34), chronic kidney disease (OR 1.32), ischemic heart disease (OR 1.31) and age (OR 1.04).

Conclusions:
Hypertension and atrial fibrillation are widespread in the elderly population and coexist in one in six people aged 65 years and older. This coexistence is associated with better blood pressure control and disease awareness.
Abstract 15274: Pediatric Valved Conduit From Biological Engineering in the Growing Lamb Model
Authors: Syedain Zeeshan , Lahti Matt , Haynie Bee , Berry James , Bianco Richard W , MacIver Robroy , Tranquillo Robert
Published: June 2023

Introduction:
A valved conduit with growth potential for pediatric patients remains an unmet need. Here we present a novel valved conduit with growth potential based on initial data in a growing lamb model. The valve is constructed from three biologically-engineered tubes of acellular collagenous matrix possessing somatic growth potential (Syedain et al., Nat Comms, 2016) using resorbable suture with each tube contributing to create a “leaflet” (Syedain et al, Sci Transl Med, 2021). This tri-tube valve previously demonstrated growth over 52 weeks when implanted interpositionally in the pulmonary artery.

Methods:
In this study, a fourth tube of the same matrix is placed around the tri-tube valve to create a tubular valved conduit. The inlet segment is cut diagonally to allow for direct attachment to the myocardium, emulating a clinical repair (see figure).

Results:
The first two lambs to date implanted in this study exhibited normal leaflet function, a pressure gradient less than 5mmHg without regurgitation or dilatation of the conduit at 12-week echocardiography (see figure). During this time the animal’s weight increased from 34±2kg to 48±1kg. The inflow pattern with this myocardial implantation was more uniform than in the previous study that used a pulmonary artery interposition implant of the just the valve (with no conduit).

Discussion:
Demonstrating integration of the conduit’s matrix to the myocardium is a key step toward a clinical trial. Previous pulmonary interposition implants of the valve, while achieving integration with the adjacent artery prior to dissolution of the Maxon suture (50% loss of tensile strength in ~3 weeks, complete by ~26 weeks), did not establish this clinically relevant point of myocardial integration.

Conclusion:
The preliminary finding is that the valved conduit exhibits excellent function at 12 weeks in the growing lamb and integration of the conduit’s matrix with the valve annulus-myocardium will likely occur.
Funding:
R01 HL107572
Abstract 15276: Polygenic Susceptibility to Dilated Cardiomyopathy Underlies Peripartum, Alcoholic, and Chemotherapy-Induced Cardiomyopathies
Authors: Maamari Dimitri J , Biddinger Kiran J , Jurgens Sean J , Gaziano Liam , Rämö Joel T , Gongora Carlos A , Hayes Dolphurs , Choi Seung H , Sarma Amy , Neilan Tomas G , Khera Amit V , Ellinor Patrick T , Aragam Krishna G
Published: June 2023

Introduction:
Rare (monogenic) variants linked to dilated cardiomyopathy (DCM) are enriched among individuals with peripartum (PPCM), alcoholic (ACM), and chemotherapy-induced cardiomyopathies (CCM), but are present in <15% of cases. Whether a common-variant (polygenic) susceptibility to DCM is also shared across these secondary cardiomyopathies is unknown.

Methods:
Cases of DCM, PPCM, ACM, and CCM were adjudicated using hospital billing codes only (in UK Biobank), or with additional chart reviews conducted by 2 medical doctors blinded to the genetic data (in Mass General Brigham [MGB] Biobank). A DCM polygenic score predicated on imaging-based measures of left ventricular structure and function was tested for association with each condition. In a subset of MGB Biobank participants with whole exome sequencing data, we determined the proportion of cases with a monogenic variant and/or a high (≥90
th
percentile) polygenic score.

Results:
In MGB Biobank (n=30,837) and UK Biobank (n=304,687), 193 cases of PPCM (n=18), ACM (n=127) or CCM (n=48) were identified. A DCM polygenic score comprising 2.3 million common genetic variants associated comparably with DCM and all three secondary cardiomyopathies (meta-analyzed p<0.001 for all) (
Figure
). Among chart-validated phenotypes in MGB Biobank, cases had higher median polygenic score percentiles than controls (Controls=50; DCM=68; PPCM=86; ACM=70; CCM=59), and a high polygenic score conferred 3.3-fold odds of any secondary cardiomyopathy (p<0.001). In the whole exome sequencing subset (N=21,378; n=65 secondary cardiomyopathy cases), 9.2% of secondary cardiomyopathy cases harbored a monogenic variant, while 21.5% had a high polygenic score (including 1.5% who had both).

Conclusion:
Individuals with PPCM, ACM, and CCM are enriched for a high DCM polygenic score, further suggesting that these conditions arise from unique, extrinsic insults acting in the context of a common, underlying genetic susceptibility.
Abstract 15289: Association Between Liver Stiffness and Prevalence of Stroke: Analysis of the National Health and Nutrition Examination Survey 2017 - 2020
Authors: Lopimpisuth Chawin , Lalitnithi Pakin , Thimphitthaya Chanattha , Pangkanon Watsachon , Wannaphut Chalothorn , Wattanachayakul Phuuwadith , Tantisattamo Ekamol
Published: June 2023

Introduction:
While cirrhotic patients increase risk of hemorrhagic and thrombotic events, association of liver stiffness with stroke remaines unclear.

Hypothesis:
Severity of liver stiffness is associated with higher prevalence of stroke.

Methods:
A cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) 2017 to March 2020 included adult participants aged 21 to 79 years. Association between prevalence of self-reported stroke and liver stiffness stratified for 4 fibrosis scores measured by Fibroscan
™
were analyzed by multivariate logistic regression.

Results:
A total of 8,416 patients with Fibroscan results were identified (mean age 49
+
16 years old; 52% female; 32% white). Overall, 377 patients (4.5%) had a stroke. The number of participants stratified by 4 fibrotic stages of mild (F0F1), moderate (F2), severe fibrosis (F3), and cirhosis (F4) were 6,243 (74.2%), 826 (9.8%), 122 (1.4%), and 155 (1.8%) patients, respectively. In multivariate logistic regression, after controlling for age, race, gender, diabetic status, body mass index (<25 vs
>
25 kg/m
2
), and high systolic blood pressure (
<
130 vs >130 mmHg), individuals with severe fibrotic liver (F3 and F4) were significantly more likely to have a stroke (adjusted odds ratio (OR) 1.64; p= 0.044; 95% confidence interval (CI) 1.01, 2.65; Figure 1). Furthermore, we found that patients with cirrhosis (F4) were the most at risk to have a stroke (adjusted OR 1.91; p= 0.037; 95% CI 1.04, 3.49; Figure 1).

Conclusions:
In this cross-sectional data, there is a graded association between severe fibrotic liver disease measured by Fibroscan
™
and elevated prevalence of stroke. Longitudinal studies including additional risk factors of stroke such as hyperlipidemia, hypertension and atrial fibrillation need to be further evaluated.
Abstract 15307: Change in Cardiovascular Health, Cardiovascular Disease, and Mortality in Patients With Diabetes
Authors: Isiozor Nzechukwu , Lloyd-Jones Donald , Valentin Eugenie , Joseph Joshua J , Lassale Camille , Jouven Xavier , Gaye Bamba
Published: June 2023

Aim:
To describe patterns of change in cardiovascular health (CVH) measured by the Life’s Simple 7 (LS7) over 6 years in participants with diabetes, and assess the association of these patterns of change with subsequent CVD and all-cause mortality.

Methods:
We conducted a long-term prospective cohort analysis (median follow-up 19 years) using the ARIC study, a community-based, biracial cohort with participants aged 45-64 years at baseline in 1987-1989. Seven markers of LS7 were collected at baseline and 6 years later: smoking, body mass index, physical activity, diet, total cholesterol, blood glucose, and blood pressure. At both time points, participants were classified as low, moderate, and favorable CVH, corresponding to presenting 0-2, 3-4, and 5-7 metrics at ideal levels.

Results:
The majority (62.2%) of participants with diabetes at baseline had a stable low CVH at both visits, whereas 12.1% had stable moderate and 0.4% stable favorable, 14.9% improved, and 10.5% worsened. Compared to those with stable low LS7, CVD and mortality risk was lower for those who showed improvement 6 years later, or started moderate and remained so, or even who deteriorated to low CVH. This was driven by favorable changes in blood pressure, cholesterol, physical activity and smoking. Compared to participants free of diabetes with a stable favorable CVH trajectory, participants with diabetes had a higher CVD and mortality risk regardless of their CVH trajectory. However, those with a favorable LS7 trajectory displayed the same excess risk as participants without diabetes with constantly low CVH.

Conclusions:
Among individuals with diabetes, maintaining or reaching ideal levels of LS7 metrics can help reduce the excess CVD incidence and mortality. A favorable CVH trajectory in people with diabetes carried approximately the same excess CVD and mortality risk than an unfavorable CVH trajectory in people free of diabetes.
Abstract 15310: Impact of Peripheral Artery Disease on Outcomes in High-Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention
Authors: Cohen Rebecca M , Spirito Alessandro , Sartori Samantha , Snyder Clayton , Nicolas Johny , Vogel Birgit , Thapi Roja , Bedel-Franklin Kayla , Beerkens Frans , Cao Davide , Sharma Samin K , Dangas George , Kini Annapoorna , Mehran Roxana
Published: June 2023

Introduction:
Peripheral artery disease (PAD) has been shown to be related to worse outcomes after percutaneous coronary intervention (PCI). Little is known about the prognostic impact of PAD in patients with concomitant high bleeding risk (HBR) undergoing PCI.

Hypothesis:
The aim of this study was to assess ischemic and bleeding complications at 1 year after PCI in HBR patients with or without concomitant PAD. We hypothesized that in HBR patients with PAD, the risk of ischemic and, to a lesser extent, bleeding complications would be higher than in non-PAD patients.

Methods:
Consecutive patients undergoing PCI with drug-eluting stent implantation (DES) at a large tertiary-care center (Mount Sinai Hospital, New York, USA) between 2012 and 2019 and fulfilling the Academic Research Consortium HBR criteria were included. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI) and stroke 1 year after PCI. The key secondary outcome was major bleeding, according to a study specific definition.

Results:
Out of 7,192 HBR patients, 975 (13.6%) had concomitant PAD. Compared to non-PAD patients, PAD patients were more likely to have cardiovascular risk factors and comorbidities and to undergo a complex PCI. MACE occurred in 93 (11.4%) patients with PAD and 382 (7.3%) without PAD. The increased risk of MACE (HR 1.59, 95% CI 1.27-1.99, p<0.001) was mainly driven by an excess of all-cause death and MI in PAD patients (
Figure 1
). Bleeding was observed in 80 (8.5%) PAD and 410 (6.9%) non-PAD patients (HR 1.25, 95% CI 0.98-1.59, p=0.066).

Conclusions:
Among HBR patients undergoing PCI with DES implantation, PAD was associated with a higher risk of MACE and a borderline increase in bleeding events.
Abstract 15341: Persistent Fifth Arch as an Aortopulmonary Connection in a Case of Tetralogy of Fallot
Authors: Negron Garcia Lianela C , Fraint Hannah , Spevak Philip C , Ravekes William J
Published: June 2023

Persistent fifth aortic arch is a heterogeneous vascular anomaly with variable anatomical presentations and physiological consequences. This unusual embryological remnant represents a management challenge, particularly in critical right sided obstructive heart lesions where accurate delineation of sources of pulmonary blood flow is essential.

This is a newborn 2 kg premature male born at 34 weeks of gestation with prenatally diagnosed tetralogy of Fallot. Post-natal echocardiogram confirmed diagnosis with evidence of moderate-to-severe pulmonary stenosis, restrictive ventricular septal defect, and a right aortic arch. CT angiogram ordered to delineate the head and neck vessel anatomy showed an exceedingly rare finding of an isolated connection of the left subclavian artery (LSCA) to the main pulmonary artery (MPA) via a left sided ductus arteriosus. Blood flowed from the common carotid arteries, through the circle of Willis, and, in a retrograde direction, into the LSCA. Prostaglandin E was initiated due to concern for ductal dependent pulmonary blood flow, but after clinical observation it was discontinued without subsequent onset of cyanosis. Repeat echocardiograms were reassuring in showing persistence of the left ductus arteriosus. The patient was discharged home at 5 weeks-old and at 4 months-old he underwent complete repair after developing progressive desaturations and worsening sub-valvar and valvar pulmonary stenosis. The surgical repair included ventricular septal defect closure, transannular patch, extensive right ventricular myomectomy and reimplantation of LSCA onto the left common carotid artery. The post-operative course was uncomplicated. This rare case of persistent fifth aortic arch with retrograde flow to the LSCA demonstrates the complementary roles of noninvasive imaging modalities in guiding medical therapy and surgical management. This unusual blood flow pattern and initial concern for duct dependent pulmonary blood flow complicated early management, but a conservative approach with repeat imaging allowed for eventual complete repair.
Abstract 15350: In-Hospital Outcomes of Transcatheter Aortic Valve Implantation in Patients With Peripheral Arterial Disease: Insights From the Nationwide Readmissions Database
Authors: Ullah Waqas , Sana Muhammad Khawar , Satti Danish Iltaf , DiMeglio Matthew , Munshi Aditya
Published: June 2023

Introduction:
Peripheral arterial disease (PAD) is associated with higher inpatient mortality among patients undergoing endovascular procedures. There is a paucity of data on the impact of PAD on clinical outcomes among patients undergoing transcatheter aortic valve implantation (TAVI).

HypothesisPAD does not alter the clinical outcomes among patients undergoing TAVI.

Methods:
The National Readmission Database (NRD) from 2015-2019 was utilized to select patients with PAD undergoing TAVI. The adjusted odds ratio (OR) of net adverse cardiovascular events (NACE), its components (mortality, stroke), and major post-procedure complications were compared using a propensity-score-matched (PSM) analysis.

Results:
Using PSM, a total of 14,925 TAVI patients, 7,386 with PAD and 7,539 with no PAD were selected. At index admission, patients with PAD had significantly higher odds of NACE (5.10% vs 3.30% OR 1.60, 95% CI 1.36 to 1.88), and in-hospital mortality (2.10% vs. 0.50% OR 4.10, 95% CI 2.88-5.83) compared with patients without PAD. However, the odds of stroke (OR 1.00, 95% CI 0.74 to 1.35), major bleeding (OR 1.15, 95% CI 0.91-1.45), acute kidney injury (OR 0.98, 95% CI 0.90-1.08), cardiac tamponade (OR 0.88, 95% CI 0.59-1.32), valvular complications (OR 1.15, 95% CI 0.78-1.69), and cardiogenic shock (OR 1.62, 95% CI 0.97-2.70) were not significantly different between the two groups. Contrary to the index admission, there was no significant difference in the 30-day outcomes of patients with PAD and without PAD undergoing TAVI.

Conclusion:
TAVI in patients with PAD might be associated with a higher risk of NACE, and in-hospital mortality during the hospitalization of the index procedure. However, these complications attenuated at a follow-up of 30-days. The risk of other post-procedure complications remained similar between the two groups.
Abstract 15366: Identifying Factors Associated With In-Hospital Mortality in Patients With Takatsubo Cardiomyopathy Utilizing a Machine Learning Algorithm
Authors: Abraham Sonu , Mathew Don , Rajendran Aiswarya , Saji Anu , Mishra Ajay K , Sherif Akil A
Published: June 2023

Introduction:
Takatsubo cardiomyopathy (TTS), also known as stress induced cardiomyopathy has a reported in-hospital mortality as high as 5% in the US. While overall risk factors have been previously reported, data regarding in-hospital contributors of mortality in TTS is lacking. In our study, we have utilized a Machine Learning (ML) algorithm to identify predictors of in-hospital mortality in patients with TTS.

Hypothesis:
Machine learning algorithms may be used to identify factors associated with in-hospital mortality in patients with TTS.

Methods:
We identified all unweighted hospitalizations with a primary diagnosis of TTS from 2016-2019 using International Classification of Diseases, Tenth Revision, diagnosis codes from the National Inpatient Sample (NIS). This is the largest publicly available database of US hospitalizations comprising a 20% stratified sample of all discharges. Data regarding demographics, hospital characteristics and associated diagnoses were abstracted and analyzed using a decision-tree ML algorithm.

Results:
We identified 7,517 patients who were hospitalized with a primary diagnosis of TTS. In this cohort, in-hospital mortality was noted to be 1.5%. 4 branches, 5 leaves and 8 nodes were identified by the decision-tree algorithm. In our model, the identified covariates associated with high in-hospital mortality were sudden cardiac arrest (p<0.001), cardiogenic shock (p<0.001), sepsis (p<0.001) and Charlson Comorbidity burden (p<0.001) in hierarchical order.

Conclusions:
ML based algorithms are being increasingly used to analyze clinical data. Our decision-tree ML algorithm was able to identify sudden cardiac arrest, cardiogenic shock, sepsis and Charlson comorbidity burden to be statistically significant predictors of in-hospital mortality amongst 77 other covariates.
Abstract 15414: Impact of Frequency and Duration of Atrial Fibrillation Events on Outcomes in Patients Undergoing Catheter Ablation
Authors: Younis Arwa , Wazni Oussama M , Yavin Hagai D , Sroubek Jakub , Hussein Ayman
Published: June 2023

Introduction:
Catheter ablation is a well-established treatment option for patients with atrial fibrillation (AF). We aimed to evaluate the impact of baseline AF events frequency, duration, and symptoms severity on AF recurrence

Methods:
The study included patients with first time AF ablation at a tertiary US center between 2013 and 2021. Patients prospectively completed a baseline and follow up survey (12 months) for patients reported outcomes assessing AF frequency, duration, and severity (AF symptom severity scale). The duration and frequency scores ranged between 0 and 9 (no AF to continuous). Patients were grouped into quartiles (Q1-Q4) based on their baseline scores. The quartile with the lowest score was used as the reference group. AF recurrence was assessed during follow up

Results:
A total of 2150 patients (age 65±9 yrs, 75% male, and 65% paroxysmal AF). At one year, only 17% of patients had AF recurrence. Frequency score: The risk for AF recurrence was similar between Q2/Q3 when compared with Q1 (Q2: HR=0.82, p=0.15, Q3: HR=0.98, p=0.91; Figure Upper), whereas patients in Q4 (score of 10) had a significant risk increase compared to Q1 (HR=1.28, p=0.047; Figure Left). Duration score: The risk for AF recurrence (Figure Middle) was similar between Q2 and Q1 (HR=0.97, p=0.83), was higher for Q3 (score ≥6 and <9; HR=1.39, p=0.015), and highest for Q4 (score ≥9; HR=1.46, p=0.002). Severity score: The baseline severity score did not predict or correlate with AF recurrence during FU. Ablation resulted in a significant reduction (≥10%) in each score category. The highest benefit was seen among the Frequency category (96% of the patients had an improvement in their score at one year), followed by duration (90%) and severity (89%)

Conclusions:
Patients’ reported high frequency, and/or high duration were associated with increased risk for AF recurrence. Following ablation, improvement in all patients’ reported outcomes was significantly higher than reported AF free survivals
Abstract 15415: Left Ventricular Unloading Reduces Right Ventricular Preload and Afterload in Patients With Acute Decompensated Heart Failure and Cardiogenic Shock
Authors: Everett Kay D , Jain Pankaj , Lee Aaron , Miyashita Satoshi , Esposito Michele , Botto Richard , Reyelt Lara A , Kawabori Masashi , Kapur Navin K
Published: June 2023

Background:
Use of the Impella 5.5 trans-valvular axial flow pump is increasing among patients with heart failure and cardiogenic shock (HF-CS) as a bridge to advanced therapies or myocardial recovery. The effect of trans-valvular left ventricular (LV) unloading on biventricular hemodynamics remains poorly understood.

Methods:
Seven patients with HF-CS underwent Impella 5.5 placement. A conductance catheter was placed first in the right ventricle (RV) then the LV to record pre-support pressure-volume loops. After insertion of the Impella 5.5, LV then RV loops were recorded within 15 minutes of device activation. Pulmonary artery catheter indices were recorded before and after Impella 5.5 activation.

Results:
Compared to baseline values, Impella 5.5 activation significantly decreased LV systolic and diastolic pressures as well as LV dP/dt(max) (Figure and Table). Impella 5.5 also significantly decreased right atrial, pulmonary (systolic/diastolic/mean) and RV diastolic pressures. Both LV and RV pressure-volume area and stroke work were not significantly changed with acute LV unloading.

Conclusions:
Trans-valvular unloading with an Impella 5.5 decreases biventricular filling pressures and reduces pulmonary pressures. These findings suggest that percutaneous LV unloading in patients with acute decompensated heart failure and cardiogenic shock may improve RV performance.
Abstract 15424: The Toxic Tango: Tyrosine Kinase Inhibitors (TKI) and Immune Checkpoint Inhibitors (ICI) Toxicities
Authors: Del Cid Fratti Juan D , Garg Rimmy , Requeña Carlos , Bhardwaj Chetan
Published: June 2023

Introduction:
ICI and TKI have several cardiotoxicity side effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that was treated with high-dose steroids and PCI.

Case Presentation:
72-year-old man presented with acute SOB and inferior STEMI. He complains of severe DOE for the past 3 months, chronic diarrhea, and altered mental status. PMH of renal cell carcinoma (RCC) limited to kidney s/p nephrectomy. Follow-up CT scan with 4cm inferior left adrenal gland mass avid for FDG-PET and IR-biopsy positive for RCC. He was started on Pembrolizumab 200mg IV q3 weeks and axitinib 5mg PO q12h for the past 5 months.

Investigation:
LHC showed a thrombotic lesion in RCA with normal rest of coronaries without evidence of atherosclerosis or bystander plaque with successful PCI-DES. TTE with inferior wall hypokinesis and moderate pericardial effusion with organized material. Elevated CRP/ESR. Despite PCI, he is unable to walk 200ft due to DOE and needs supplemental O2. VQ scan low % for PE, PFT mild obstructive disease with severe reduction DLCO, and HRCT moderate emphysema, bronchial/ septal thickening, and normal hemodynamics in RHC. CMR demonstrated moderate pericardial effusion with internal debris, LVEF 38%, myocardial edema, and delayed gadolinium enhancement from base to apical inferior wall.

Treatment:
Empirical trial of IV-methylprednisolone 500mg IV q12 was started with drastic improvement of shortness of breath, resolution of AMS, ESR/CRP, and discontinuation of oxygen. Follow-up TTE with normal LVEF and resolution of pericardial effusion.

Conclusions:
ICI-Myocarditis is a severe irAE. The diagnosis requires clinical suspicion and exclusion of other cardiac conditions due to the high fatality rate. Early recognition and prompt treatment are needed to improve mortality. TKI-related arterial-thromboembolic events is not common but if present different therapy options should be offered.
Abstract 15427: Reduction of Epicardial Fat, Clinical Risk Factors & Symptomatology in Paroxysmal AF Patient With Severe Aortic Stenosis and Metabolic Syndrome via Mobile Cardiometabolic Health & Weight Loss Program
Authors: Barnes Jessica , Dembrowski Gerald , Vallurupalli Srikanth , Malkawi Abdallah , Devabhaktuni Subodh , Paydak Hakan , Balogh Julius , Mounsey John
Published: June 2023

Atrial fibrillation (AF) is dependent on epicardial fat (EpF) accumulation and infiltration. Complementary therapeutic strategies specifically targeting EpF present an opportunity for slowing progression and reversing the course of AF. A 73-year-old man with a history paroxysmal AF (managed by rate control/anticoagulation), severe aortic valve stenosis (AVS, area 1cm
2
, EF 55%), controlled hypertension, diabetes, and obesity (BMI 37.9) completed a 2-month cardiometabolic health program (CHP). The ‘tech plus touch’ CHP, delivered via a smartphone, utilized a comprehensive approach with physiological, nutritional, and behavioral components. Along with patented dietary regimens and nutritional supplementation implemented with personalized treatment algorithms, the CHP included direct daily engagement (messaging & telehealth) with a staff clinician via the HIPAA compliant mobile app. Patient data visible to both the patient and staff clinician was synced automatically via Bluetooth-linked devices. EpF dropped by 25.5% over 9w (transthoracic echo, Fig1). BMI, visceral adiposity, and body fat were significant reduced, while lean body mass (LBM), muscle mass (MM) and intracellular fluid (ICF, a validated surrogate of chronic inflammation) improved (Fig1). Encouragingly, LBM, MM, and ICF improvements were unusual and particularly large in this older, physically inactive patient. Other clinical risk factors improved including diabetes, kidney function and inflammation. The patient reported resolution of chest pain and dyspnea, improved cardiorespiratory fitness, and began aerobic exercise. Our data demonstrate a nonpharmacologic complementary approach produces significant reductions of EpF and modifiable risk factors linked to hypertension, diabetes, and chronic inflammation in an AF patient with AVS and metabolic syndrome. Whether this will lead to a reduction in AF burden or conversion to persistent AF, remains to be determined.
Abstract 15432: Post-Operative Systolic Dysfunction Following Aortic Root Replacement Surgery in Patients With Marfan Syndrome
Authors: Connor Brynn S , Algaze Claudia , Miller D C , Liang David , Collins Ronnie T
Published: June 2023

Introduction:
Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients requiring prophylactic aortic root surgery for management of progressive aortic dilation. Given evidence for intrinsic myocardial dysfunction in MFS, patients may be at an increased risk of developing post-operative dysfunction and related cardiovascular complications following cardiac surgery. Our aim was to determine the prevalence, persistence, and long-term outcomes of post-operative ventricular dysfunction in MFS following aortic root replacement surgery.

Methods:
All adult patients with a confirmed diagnosis of MFS who underwent aortic root replacement surgery at Stanford from January 1995 to December 2021 were included. Post-operative systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) <55% on transthoracic echocardiography at hospital discharge. Potential genetic, operative, and cardiac risk modifiers were also recorded.

Results:
There were 274 patients with MFS (64% male, 71% White) who underwent aortic root replacement surgery, followed over a median duration of 11 years (IQR 5, 16). Post-operative systolic dysfunction was present in 93 patients (33.9%), with a median LVEF of 46.9% (IQR 42.0, 50.5), median decrement in LVEF of 10.9% (IQR 5.5, 19.0), and median duration of persistence of 22 months (IQR 8.0, 57.3). There was no significant association with traditional operative nor cardiovascular risk variables. Patients with a reduced pre-operative LVEF were three times more likely to have worsened post-operative systolic function (OR=3.6, 95% CI=1.2-10.8, p=0.02), demonstrated more severe systolic impairment (LVEF <30%: OR 1.8, 95% CI=1.4-26.1, p=0.02), and exhibited persistent dysfunction (≥5 years: OR 1.6, 95% CI=1.8-14.6, p=0.002).

Conclusions:
Post-operative systolic dysfunction is common in patients with MFS following aortic root replacement surgery. A reduced pre-operative LVEF is associated with more severe and protracted post-operative impairment, and therefore may be an important consideration for surgical timing.
Abstract 15464: Mitochondrial Function of Adventitial Fibroblasts in Pulmonary Hypertension is Regulated Through Sirt3 Deacetylase Activity
Authors: Li Min , Dobrinskikh Evgenia , Zhang Hui , Hu Cheng-Jun , Stenmark Kurt R
Published: June 2023

Introduction:
Pulmonary hypertension (PH) is a heterogeneous and life-threatening cardiopulmonary disorder in which mitochondrial dysfunction drive pathogenesis. Although metabolic changes in PH draw attention of extensive investigation, the underlying mechanisms remain unclear.

Hypothesis:
Decreased Sirt3 mitochondrial deacetylase activity leads to increased mitochondrial enzyme acetylation level and mitochondrial dysfunction in pulmonary artery adventitial fibroblast cells isolated from IPAH patients (PH-Fibs).

Methods:
1) qPCR and western blot to examine Sirt3 gene and protein levels in PH-Fibs and CO-Fibs, 2) western blotting of isolated mitochondrial protein acetylation level to examine the Sirt3 deacetylase activity, 3) immunostaining of mitochondrial SOD2 (direct target of Sirt3) acetylation level in lung tissues from PAH patients to examine Sirt3 deacetylase activity in vivo, 4) respiratory analysis and fluorescent lifetime imaging microscopy (FLIM) to analyze the glycolytic and mitochondrial function in cells, 5) overexpressing Sirt3 and supplement NAD
+
to investigate the therapeutic potential of regulating mitochondrial enzyme acetylation level and mitochondrial function in PH-Fibs.

Results:
PH-Fibs have decreased Sirt3 mRNA and protein levels compared to CO-Fibs. NAD
+
, a Sirt3 co-factor, is also decreased in PH-Fibs. Increased mitochondrial protein pan-acetylation levels and mitochondrial specific Sirt3 target (MnSOD2) were identified in cultured PH-Fibs, as well as lung vasculatures of IPAH patients, indicating the decreased mitochondrial deacetylase activity of Sirt3 in vitro and in vivo. We demonstrated increased glycolytic capacity and impaired mitochondrial function in PH-Fibs compared to CO-Fibs. Finally, by overexpressing Sirt3 level and at the same time increase NAD
+
availability, we proved that Sirt3 and NAD
+
can serve as therapeutic methods to synergistically improve mitochondrial function by regulating mitochondrial enzyme acetylation level in PH-Fibs.

Conclusions:
This study demonstrated that the mitochondrial deacetylase activity of Sirt3 as a critical mechanism regulating mitochondrial protein acetylation and mitochondrial function of fibroblast cells in IPAH patients.
Abstract 15469: Activation of Sting Pathway Promotes Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Wall
Authors: Chakraborty Abhijit , Li Yanming , Zhang Chen , Li Yang , Rebello Kimberly , Zhang Lin , Chen Kaifu , Vasquez Hernan , Coselli Joseph S , LeMaire Scott A , Shen Ying H
Published: June 2023

Introduction:
Smooth muscle cell phenotypic alteration is a prominent feature of aortic aneurysms and dissections (AAD) that causes the loss of functional, contractile, smooth muscle cells (SMCs) and subsequent aortic dysfunction. However, SMC phenotypic alteration in AAD and the underlying mechanism is poorly understood.

Hypothesis:
Stress on the aorta induces a phenotypic switch in SMCs from a contractile role to a pro-inflammatory role that promotes cell dysfunction and death.

Methods:
We performed single-cell RNA and ATAC sequencing (scRNA-seq, scATAC-seq) of ascending aortic tissues from patients with sporadic ascending AAD and organ donor controls, alongside murine aortic tissues from a sporadic AAD model and wild-type mice. The role of the STING pathway in SMC phenotypic alterations was studied in human aortic SMCs. Chromatin immunoprecipitation assays were used to study epigenetic regulation

Results:
Significant SMC transformation from a contractile phenotype to a pro-inflammatory, pro-fibroblast, and pro-death phenotype was seen in scRNA-seq of aortic tissues from AAD patients and a sporadic AAD murine tissue. Our sc-ATACseq indicated that SMC transformation was partially controlled by chromatin remodeling of these genes, and IRF3 was identified as a key transcriptional factor for the reduction of chromatin accessibility of contractile genes, but induction of chromatin accessibility of inflammatory genes. In cultured SMCs, cytosolic DNA, through STING-TBK1 signaling, activated IRF3, which directly bound cis-elements of contractile genes, and recruited EZH2 to induce repressive H3K27me3 modification, leading to SMC gene suppression. Activated IRF3 also induced inflammatory gene expression. SMC-Sting deficiency prevented proinflammatory phenotypic switch in the sporadic AAD mouse model and restored contractile phenotype.

Conclusion:
We highlight an epigenetic pathway responsible for SMC dysfunction that induced SMC gene suppression and SMC phenotype changes and identified STING-TBK-IRF3-EZH2 as key signaling that suppresses SMC genes. To the best of our knowledge, this is the first study reporting that the STING pathway contributes to AAD development by SMC transition from a contractile to an inflammatory phenotype.
Abstract 15476: Methadone-Related Sudden Death in the Community
Authors: Seifer Madison , Norby Faye L , Sargsyan Arayik S , Uy-Evanado Audrey , Dizon Bernadine , Bhanji Ziana , Hurst Sean , Young Christopher , Jui Jonathan , Reinier Kyndaron , Chugh Sumeet S
Published: June 2023

Introduction:
Non-toxic levels of methadone have been associated with ventricular dysrhythmias and sudden death, but current community-based data are lacking. We studied demographics and resuscitation circumstances at the time of cardiac arrest in these individuals.

Methods:
We prospectively ascertained all residents of Multnomah Co., OR (2002-18) and Ventura Co., CA (2015-21) who suffered out-of-hospital cardiac arrest and had toxicology reports available. We excluded individuals under age 18 or with evidence of recreational drug use or drug overdose. Methadone levels were captured on toxicology reports from the medical examiner and resuscitation variables were obtained from emergency medical services. We used logistic regression to compare demographics and resuscitation features in those with and without methadone.

Results:
Of the 789 subjects who met criteria, the mean (SD) age was 49 (13) years, 34% were females, and 85 (11%) had therapeutic levels of methadone (Table). After adjusting for age, females were 2.26 times more likely to have methadone on their toxicology report (1.42-3.57; p-value=0.0005). Subjects with methadone-related deaths were younger and 3.5 times more likely to suffer cardiac arrest in a home setting compared to those without methadone. Although the prevalence of night-time arrest was similar in those with and without methadone, those with methadone were more likely to have an unwitnessed event or no resuscitation attempted. When resuscitation was attempted, 97% of those with therapeutic methadone levels had a non-shockable presenting rhythm.

Conclusion:
Although males account for 66% of overall sudden death events, females were twice as likely to have a methadone-related sudden death compared to males. Methadone-related cardiac arrests are difficult to resuscitate. These findings highlight the need to enhance primary prevention of methadone-related sudden deaths, and a renewed investigative focus on higher risk in women.