bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11240: Capillary Rarefaction and Right Ventricular Dysfunction in Advanced HFrEF: Human Tissue Histomorphometry Analysis
Authors: Melenovsky Vojtech , Kucera Tomas , Mracek Tomas , Havlenova Tereza , Kaplanova Vilma , Cunatova Krystina , Benes Jan , Pierzynova Aneta , Å rÃ¡mek JaromÃr , Kautzner Josef
Published: March 2022

Introduction:
Right ventricular dysfunction (RVD) limits survival in heart failure (HF). Besides pulmonary hypertension (PH), load-independent mechanisms may contribute to RVD. In experimental PH, loss of myocardial capillary density (rarefaction) was implicated in the faster decline of RV function.

Hypothesis:
To elucidate the role of rarefaction in development of RVD in HFrEF.

Methods:
We examined RV fractional area change (RV FAC%) prior heart Tx (median -57 days) in 124 consecutive HTx candidates (non-LVAD) and harvested RV free wall at HTx from patients in the bottom (Q1: 10-17%) and top (Q4: 32-42%) quartiles of pre-HTx RV FAC%. As controls (Con), we obtained RV samples from 20 unused heart donors. Quantitative histomorphometry and mRNA gene expression were studied.

Results:
HF (65% non-ischemic) and Con were matched by similar age, gender and BMI. HF patients had larger and more dysfunctional RV (RVD1 46 vs 32 mm, p<0.001, RV FAC 25±10%). Compared to Con, RV from HF displayed significant upregulation of genes for PDK4 (Pyruvate Dehydrogenase Kinase4), NPPA (Natriuretic peptide A), BDH1 (β-OH-butyrate dehydrogenase), and downregulation of MYH6 (Myosin Heavy Chain 6). In HF vs Con, RV CM diameter was increased (25±6 vs 15±4 μm, p<0.001), but RV capillary density was lower (939±474 vs 1457±670 n/mm
-2
, p=0.007), even if adjusted to CM diameter (39 vs 102 mm
-1
, p=0.0005) or area (Fig). HF patients from Q1 and Q4 RV FAC differed by higher PH (mPA 37 vs 31 mmHg, p=0.01), larger RV size (48 vs 43 mm, p=0.01) and higher PCWP (27 vs 22, p=0.002), but there was no difference in capillary density (unadjusted or per CM diameter/area, Fig) or gene expression profile, HF etiology or comorbidities.

Conclusions:
Compared to Con, RV of HF patients shows reduced capillary density, metabolic and myofilament remodeling. Yet, HF patients with lower RV FAC% do not differ from those with less impaired RV function, suggesting that capillary rarefaction
per se
does not explain progression of RVD in HF.
Abstract 11251: Warfarin versus Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus; A Multicenter Retrospective Observational Study
Authors: Al-abcha Abdullah , Clay Shannon , Wang Ling , Prasad Rohan M , Salam Mohammad F , Srivastava Shaurya , boumegouas manel , Abela george , Essa Essa M M
Published: March 2022

Introduction:
Left Ventricular (LV) thrombus formation is seen in some patients with severely reduced ejection fraction. Current guidelines recommend the use of warfarin in patients with LV thrombus. However, safe and effective warfarin use is often inconvenient and burdensome to some patients.

Hypothesis:
Direct oral anticoagulants (DOACs) are as effective as warfarin in the treatment of LV thrombus.

Methods:
We performed a multicenter retrospective analysis of adults admitted between January 2015 and December 2021 and diagnosed with LV thrombus. The primary outcome was thrombus resolution. Secondary outcomes included all-cause mortality, bleeding events and stroke or systemic embolism (SSE). Chi-square test was used to compare categorical variables. T-test was used for continuous variables comparison. Logistic regression was used to evaluate primary and secondary outcomes to control confounding factors such as demographic and comorbidity information.

Results:
A total of 194 patients were included, 48 (24.7%) of whom were treated with DOACs. The mean age was 61.6 ±13.3 years and 46 (23.7%) of the population were females. The two arms had no significant differences in age, sex, BMI, CHA2DS2-VASc score, history of DM, HTN, atrial fibrillation or ischemic cardiomyopathy. The rate of thrombus resolution (DOACs 58.3% vs warfarin 66.4%, p=0.309) and bleeding events (DOACs 14.6% vs warfarin 13.7%, p=0.878) were similar in both arms. The rate of SSE was numerically lower in the DOACs arm without statistical significance (DOACs 8.3% vs warfarin 15.07%, p=0.309). All-cause mortality was significantly higher in the DOACs arm (DOACs 22.9% vs warfarin 10.3%, p=0.026). In multivariate analysis, there was no significant effect of using warfarin on thrombus resolution, all-cause mortality, bleeding evens, and SSE (Figure).

Conclusions:
In our retrospective analysis, DOACs had similar efficacy and safety when compared to warfarin in the treatment of LV thrombus.
Abstract 11254: Lin28a Promotes Persistence of Mononucleated Diploid Cardiomyocytes and Cardiac Regeneration After Injury
Authors: Rigaud Vagner O , Hoy Robert , Kurian Justin , Zarka Clare , Behanan Michael , Khan Mohsin
Published: March 2022

Developmental cardiac tissue holds a remarkable capacity to regenerate after injury and consists of regenerative mononuclear and diploid cardiomyocytes (MNDCMs). Upon maturation, MNDCMs become binucleated or polyploid and exit the cell cycle. Interestingly, CM metabolism undergoes a profound shift that coincides with the cessation of regeneration in the postnatal heart. However, whether reprogramming metabolism promotes persistence of regenerative MNDCMs enhancing cardiac function and regeneration after injury is unknown. Here, we identify a novel role for RNA-binding protein LIN28a, a master regulator of cellular metabolism, in cardiac regeneration following injury. LIN28a was found as primarily active during cardiac developmental stages and rapidly decreases after birth. LIN28a reintroduction at P0, P3, P5, and P7 decreased maturation-associated polyploidization, nucleation, and cell size enhancing CM cell cycle activity (Ki67+, pHH3+, and AurB+ cells) in LIN28a transgenic pups compared to WT littermates. Moreover, LIN28a overexpression extended CM cell cycle activity beyond P7 concurrent with increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression attenuated CM apoptosis, enhanced CM cell cycle activity, cardiac function, and survival in mice 12 weeks after myocardial infarction compared to WT littermate controls. Alternatively, LIN28a small molecule inhibitor attenuated the pro-regenerative effects of LIN28a on the heart. Mechanistically, Neonatal rat ventricular myocytes (NRVMs) overexpressing LIN28a showed increased glycolysis, ATP production, and activity of metabolic enzymes compared to control. Collectively, LIN28a reprograms CM metabolism and promotes persistence of regenerative MNDCMs in the injured heart enhancing pro-regenerative processes thereby linking CM metabolism to the regulation of ploidy/nucleation and regeneration in the heart.
Abstract 11256: Longitudinal Changes of Left Ventricular Hemodynamics and Geometry After Myocardial Infarction in a Chronic Swine Model with Functional Mitral Regurgitation
Authors: Onohara Daisuke , Silverman Michael , Corporan Daniella , Xu Dongyang , Sreerangathama Suresh Kirthana , Padala Muralidhar
Published: March 2022

Introduction:
Ischemic mitral regurgitation (IMR) is a frequent complication of left ventricular (LV) pathological remodeling after myocardial infarction (MI), which doubles morbidity and mortality. Longitudinal LV remodeling after an MI is not fully understood, therefore large animal studies are needed. In this study, we developed a chronic swine model with IMR and investigated temporal changes of LV remodeling with transesophageal echo (TEE) and pressure-volume (PV) loops.

Methods:
Yorkshire swine (n=14) underwent induction of a lateral MI through ethanol injection percutaneously into the left circumflex artery (LCX) distal to the first obtuse marginal branch. The animals were survived for 3 months with monthly follow-up TEE. PV loops were performed at baseline, immediately after MI induction, and 3 months post-MI (
Fig.A
).

Results:
12 animals survived the MI procedure and developed IMR (average MR grade was 2.6±1.0). LCX occlusion was confirmed with coronary angiogram at 3 months post-MI. EDV and ESV were significantly increased at 3months compared to baseline (156.5±53.0 vs 63.3±7.2ml, p<0.0001, and 83.2±31.4 vs 25.5±5.1ml, p<0.0001, respectively). EF decreased 39.7±7.2% just after infarction compared to 59.4±4.3% at baseline (p=0.0001) and increased at 1 and 2 months, then decreased again at 3 months (53.6±8.1, 55.9±6.3, and 46.7±7.6%, respectively) (
Fig.B
). In invasive hemodynamics, end-systolic elastance, preload adjusted dP/dt
max
, and end-diastolic pressure-volume relationship significantly decreased at 3 months indicating both systolic and diastolic dysfunction. Arterial elastance at 3 months was significantly lower than baseline indicating a reduction of afterload due to MR (
Fig.C
).

Conclusions:
A lateral MI resulted in an acute reduction in EF, followed by development of IMR, chronic LV dilation, and decreased systolic and diastolic function over 3 months. Temporary improvement of EF after MI may indicate reduced afterload due to MR.
Abstract 11258: Engaging Diverse Patients, Caregivers, and Clinicians as Partners to Identify Disease Management Related Challenges in Atrial Fibrillation:
A Qualitative Study Utilizing Human-Centered Design Methodology
Authors: Isakadze Nino , Molello Nancy , Spragg David D , Gao Yumin , Spaulding Erin , MacFarlane Zane , Michos Erin , Marine Joseph E , Berger Ronald D , Calkins Hugh G , Martin Seth S
Published: March 2022

Introduction:
Despite advances in atrial fibrillation (AF) management, patients with AF continue to experience poor quality of life and adverse outcomes. Engagement of patients, caregivers, and clinicians to identify challenges in AF management can inform strategies to improve quality of life and improve AF related outcomes.

Methods:
We conducted virtual Human Centered Design (HCD) sessions with a) patients with AF and their caregivers to understand challenges in living with AF, and b) clinicians caring for patients with AF to identify difficulties encountered in AF management. During HCD sessions, we engaged participants to answer open-ended questions. Transcripts of audio recorded sessions were coded and emerging themes were identified.

Results:
8 patients (25% African American, 13% Asian), 3 caregivers, and 7 clinicians participated in HCD sessions. Median (interquartile range) patient age was 69 years (58 - 78). Major themes from the patient and caregiver perspective included inadequate education on AF, lack of guidance on AF risk factor modification, lack of support networks, and absence of systems to guide patients when experiencing recurrent AF episodes. Major themes from the clinician perspective were complementary to patient and caregiver input. Themes included inadequate patient education due to limited time clinicians can spend with patients, lack of AF risk factor modification programs, and lack of streamlined services to allow timely communication with patients without increasing the administrative burden for physicians (Figure 1).

Conclusions:
A diverse group of patients, their caregivers, and clinicians identified lack of adequate education, guidance on AF risk factor modification as well as poorly structured patient-clinician communication as major challenges in AF care. Our findings are informing development of mobile health application addressing identified challenges with a goal to improve quality of life and adverse AF outcomes.
Abstract 11265: Sex-Specific Response to Endothelin-1 Overexpression Mediates Thoracic Aortic Aneurysm Development
Authors: Lee-Kim Vivian , Atri Deepak , Vellarikkal Shamsudheen , Paradis Pierre , Schiffrin Ernesto L , Gupta Rajat
Published: March 2022

Introduction:
Thoracic aortic aneurysms (TAAs) are common diseases associated with high morbidity and mortality. Although TAAs are more common in men, women have worse outcomes and dissect at smaller aortic diameters. Endothelin-1 (ET-1) is the most potent vasoconstrictor in humans, and an important mediator of vascular stiffness and tone. ET-1 levels are increased in patients with TAA, and genetic variants that affect ET-1 production and receptor expression are associated with vascular diseases. Though ET-1 levels do not differ between men and women with TAA, it is unknown if response to ET-1 mediates sex-specific differences.

Hypothesis:
ET-1 has different effects on vascular stiffness and aortic dissection risk in men and women.

Methods:
Angiotensin-II (AngII) was delivered subcutaneously at 1 ug/kg/min dose and rate using osmotic pumps for 28 days in endothelial cell-specific ET-1 transgenic (eET-1) and matched WT control mice. We measured blood pressure, aortic stiffness, and aortic size at the end of the study.

Results:
We observed marked sex-specific ET-1 effects on TAA. Despite elevated blood pressure in all animals that received AngII (Fig1A), we observed increased aortic stiffness in male eET-1 mice (+1.5 m/s eET-1 vs. +0.74 m/s WT) but decreased aortic stiffness in female eET-1 mice (-1.9 m/s eET-1 vs. +0.69 m/s WT), measured by pulse wave velocity (Fig1B). Consistent with these results, aortic diameter was only increased in male eET-1 mice (+0.61 mm eET-1 vs. +0.11 mm WT) but not in female eET-1 mice (+0.06 mm eET-1 vs. +0.11 mm WT) (Fig1C). Significantly, 2 of 3 male eET-1 animals died before 28 days from dissected TAAs, whereas all females survived the length of the study.

Conclusions:
In the AngII-TAA model, there is a sex dimorphic effect of ET-1 overexpression. Male mice have greater vascular stiffness and develop TAA in response to the same level of ET-1 as in matched female mice. This difference may explain the increased incidence of TAA in men.
Abstract 11266: Murine Adult Epicardium Requires Hypoxia for Progenitor and Multipotency Ability
Authors: Sayed Angeliqua , Turoczi Szimonetta , Soares-da-Silva Francisca , Marazzi Giovanna , Hulot Jean S , Sassoon David , Valente Mariana
Published: March 2022

Introduction:
The epicardium is a source of the coronary vasculature and stroma during heart development. Although quiescent in the physiological adult heart, increasing evidences indicate the potential epicardium activation and differentiation into its progeny after cardiac injury; however, this remains debated.

Hypothesis:
We hypothesize that in vivo hypoxia exposure can mimic the embryonic cardiac profile and prime the adult epicardial progenitor cell to a more immature profile.

Methods:
Perinatal and adult BL6 and

Pw1
nLacz

hearts were used to track the expression of PW1 - progenitor cell marker - together with cell surface proteins. In vivo hypoxia (10% O
2
) exposure was used to stimulate the adult heart. Histology, protein expression profiles and single cell analysis were assessed. Freshly FACS isolated Gp38
+
PW1
+
epicardial cells were cultured to determine their progenitor cell potential (clonogenicity, self-renewal and cell fate potential).

Results:
Here, we report that PW1 expression decreases during postnatal life, but is maintained in the cardiac hypoxic niche epicardium and subepicardium. Adult mice exhibit increased PW1 expression in epicardial/subepicardial cells and endothelial cells in response to hypoxia. The epicardium and subepicardium are activated to undergo cell proliferation and re-express a subset of embryonic genes in response to hypoxia. We established a new in vitro model to study purified PW1
+
/Gp38
+
epicardial cells, and we found properties of clonogenicity, self-renewal and multipotency (fibroblast, smooth muscle and endothelial cells) at single cell level in the developing epicardial cells. Cell fate potential towards an endothelial profile is dependent upon low levels of oxygen, and the in vitro ability to grow in culture is restore after in vivo priming of the adult heart.

Conclusions:
In conclusion our data support that the resident PW1
+
/Gp38
+
epicardial cells are a reminiscent progenitor population in adult mammalian heart that can be reactivated by exposure to hypoxia, highlighting the potential therapeutic role of hypoxia in regenerative medicine.
Abstract 11272: Barriers and Enablers of Rheumatic Heart Disease Care in a Resource Limited Setting
Authors: Pulle Jafesi , Nalubwama Hadija , ATALA JENIFER , Namara Rebecca , Sarnacki Rachel , Ndagire Emma , beaton andrea , Sable Craig A , Watkins David , Okello Emmy
Published: March 2022

Introduction:
Rheumatic heart disease (RHD) has nearly been eradicated in wealthy nations but remains a significant public health concern in low-resource countries like Uganda. Many people living with RHD is these settings have not been diagnosed and many who are diagnosed have late-stage disease requiring surgery, an expensive intervention.

Objectives:
To explore the barriers and enablers to RHD care in a resource limited setting.

Methods:
This was a qualitative study. We held in-depth interviews among 36 RHD patients randomly selected from a computer-generated list of patients enrolled in the RHD registries in the Northern, Central, and South-western regions. The selected participants were interviewed by trained qualitative research staff. All interviews were tape recorded and transcribed verbatim. Data were analyzed by thematic content analysis and useful codes were generated by both inductive and deductive approaches. Generated codes were collapsed into themes. Coding was done by 3 independent researchers who compared their results and agreed on one codebook which was updated iteratively.

Results:
Barriers to care included financial constraints, high cost of medicines, poor access to RHD diagnostics, misdiagnosis, poor access to drugs, high cost of cardiac medicines and high costs of travel to health facilities. Enablers of RHD care included the desire to live, availability of drugs, diagnostics and healthcare workers at RHD clinics, good attitude, counseling and education by health workers, subsidised costs of services at RHD clinics, reminder systems and access to RHD services at nearer facilities.

Conclusion:
Enhancing enablers and mitigating barriers may improve access to RHD care in resource limited settings and significantly reduce the burden of disease.
Abstract 11274: All-Cause Mortality Association of Right Ventricular Free Wall Longitudinal Strain and Strain Rate in Acute Pulmonary Embolism Patients
Authors: Jain Vaibhav , Quintero-Martinez Juan , Madera Sandra C , Vlazny Danielle , Wysokinski Waldemar E , Houghton Damon , Villarraga Hector R
Published: March 2022

Introduction:
Right ventricle (RV) dysfunction linked with acute Pulmonary embolism (PE) is associated with significant mortality. Several studies have documented use of RV free wall strain (RVS) for assessing mortality, but RV free wall systolic (RVSRs) and early diastolic strain rate (RVSRe) have not been explored.

Hypothesis:
The study aims to assess the RV function in longitudinal domain of contractility using 2 D speckle tracking echocardiography and evaluate if it was able to predict all-cause mortality at 30 days.

Methods:
This is a single center prospective study done between November 2012 to June 2020. 293 adult patients with acute PE having echocardiogram performed within 24 hours were enrolled and baseline comorbidities were recorded. 2 D Speckle tracking echocardiography was performed offline. Multiple logistic regression analyses and ROC were performed to evaluate if RV Strain (RVS) and strain rate (systolic-SRs, early diastolic-SRe) were able to predict all-cause mortality at 30 days.

Results:
Mean age was 65 ± 15 years, 60.7 % males and 41% had coronary artery disease, 29% had cancer and 11% had COPD. Mean free wall (FW) RVS was -19.7±7.7%, FW RV SRs was -0.9±0.4 s
-1
, FW RV SRe was 0.8±0.3 s
-1
. (Figure A) All-cause mortality was present in 11 patients (3.8%) at 30 days, 17 (5.8%) at 3 months and 29 (9.9%) at 6 months. In the Univariate analysis, FW RVS and FW RVSRs were significantly associated with 30 days all-cause, but after adjusting for age, cancer, and COPD, only FW RVSRs remains significant (p=0.02) with an AUC to predict 30-day all-cause mortality of 0.73 (95% CI 0.54-0.88) a cut-off value of -0.7 had a sensitivity of 73% and specificity of 64% (Figure B)

Conclusions:
The study demonstrated that RV Free wall SRs measured by 2 D STE is a good prognostic indicator for 30 days all-cause mortality in patients with acute PE. This novel modality could be used for risk stratification in the setting of acute PE.
Abstract 11276: Safety and Tolerability of ALN-AGT, an RNA Interference Therapeutic Targeting Hepatic Angiotensinogen Synthesis, in Hypertensive Patients During Sodium Depletion or Irbesartan Coadministration
Authors: Huang Stephen , Taubel Jorg , Desai Akshay S , Cheng Yansong , Habtemariam Bahru
Published: March 2022

Introduction:
We have recently reported that ALN-AGT, a subcutaneous (SC) investigational RNA interference therapeutic targeting hepatic angiotensinogen (AGT) synthesis, reduced BP and was generally well tolerated in a single ascending dose study of hypertensive patients. To further assess its safety profile, additional studies have been initiated to test the effects of peak ALN-AGT pharmacology during salt depletion or irbesartan add-on treatment.

Methods:
As part of a Phase 1 program, hypertensive patients (mean seated SBP of >130 and ≤165 mm Hg after washout of antihypertensive medication) were given a single dose of ALN-AGT 800 mg SC that has been shown to reduce serum AGT by ≥95%. At Day 43 (corresponding to expected peak serum AGT reduction), these ALN-AGT-treated patients were admitted to receive interventions of a 7-day sodium restricted diet (10 mmol sodium day) or a 14-day add-on treatment regimen with the angiotensin receptor blocker irbesartan 300 mg by oral administration daily.

Results:
In the salt depletion cohort, 12 patients (mean age 56 years, 75% male, 25% black, mean baseline 24-h SBP 141+/- 8 mm Hg) have been dosed 2:1 with ALN-AGT or placebo SC in advance of the sodium restricted diet. In the irbesartan add-on cohort, 10 patients (mean age 55 years, 30% male, 30% black, mean baseline 24-h SBP 147 +/- 8 mm Hg) have received ALN-AGT in advance of irbesartan add-on. The study has completed patient enrollment and interventions with no patient discontinuations due to AEs. The data analysis is ongoing at the time of abstract submission.

Conclusions:
This ongoing study will provide insight into ALN-AGT tolerability during potential augmented pharmacology, using salt restriction to test ALN-AGT’s effects during reduced extracellular fluid volume and irbesartan coadministration to assess the effects of ALN-AGT’s liver-specific AGT silencing during angiotensin II receptor blockade. Data on tolerability, laboratory safety monitoring, serum AGT reduction, RAAS-related biomarkers, and blood pressure will be presented.
Abstract 11280: Effect of Homelessness on Incidence of Autopsy-Defined Causes of Presumed Sudden Cardiac Death: Insights from the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) Study
Authors: Ramakrishna Satvik , Salazar James W , Siegel Emily , Olgin Jeffrey E , Moffatt Ellen , Tseng Zian H
Published: March 2022

Introduction:
Prior studies report higher cardiovascular mortality in persons experiencing homelessness (PEH), but presume cardiac cause of death (COD) from EMS records or death certificates. The effect of homelessness on autopsy-defined SCD is unknown. In this prospective postmortem study of all SCDs in San Francisco (SF) County, we hypothesized a greater incidence of presumed SCD in PEH, but more non-cardiac COD on autopsy.

Methods:
Between 2/2011 - 3/2014, all incident World Health Organization-defined (presumed) SCDs ages 18-90 were autopsied via active surveillance of out of hospital deaths in the POST SCD Study. A multidisciplinary committee adjudicated COD. Autopsy-defined SCDs had no extra-cardiac COD (e.g., overdose, pulmonary embolism, stroke). Homeless status was determined from medical records; rates of presumed and autopsy-defined SCD were compared to those for housed individuals. The countywide homeless population was determined from the 2013 SF Homeless Count and Survey.

Results:
We identified 525 presumed SCDs over 37 months: 36 (7%) were PEH and 489 (93%) were housed. Presumed SCDs in PEH were younger than housed subjects (56.5 ± 9.9 v. 63.2 ± 14.6 years), more often male (97% v. 67%), less likely to be Asian (0% v. 22%) or have dyslipidemia (3% v. 32%), but more likely to have alcohol (58% v. 21%) and substance use disorder (44% v. 13%, p<0.01 for all). The presence of psychiatric disorders was similar between groups. Among presumed SCDs, PEH had a lower proportion of autopsy-defined SCDs than housed individuals (9/36 [25%] v. 306/489 [63%]), with more non-cardiac COD including aspiration, aortic dissection, occult overdose, and infection (p<0.05 for all). Observed incidence rates for presumed SCD were 181.4 v. 22.7 per 100,000 person-years (IRR 8.01, p<0.01) in PEH v. housed individuals, and 45.4 v. 14.2 per 100,000 person-years (IRR 3.20, p<0.01) for autopsy-defined SCD.

Conclusion:
In this 3-year comprehensive postmortem study of all incident SCDs in a diverse urban setting, homelessness was associated with >3-fold higher risk of autopsy-confirmed SCD and 8-fold higher risk of sudden mortality overall. Only one-fourth of presumed SCDs in PEH were autopsy-confirmed SCDs, while one-third of non-cardiac causes were due to occult drug overdose.
Abstract 11283: Prevalence of Metabolic Syndrome and Associated Risk Factors in Women Living with HIV
Authors: Arrais Claudia , Pires Nilviane , Azoubel Luana M , Lima Cindy , Barros Allan Kardec K
Published: March 2022

Introduction:
The presence of Metabolic Syndrome (MetS) increases the risk of developing cardiovascular diseases and diabetes. People living with HIV (PLHIV) using antiretrovirals (ART) have a higher cardiometabolic risk and, consequently, a higher risk of presenting MetS. Thus, the present study evaluated the prevalence of MetS in PLHIV women.

Methods:
This is a cross-sectional study, carried out with 123 PLHIV women who use ART, aged 21 to 55 years, from a city in the Northeast of Brazil. Were evaluated clinical variables such as age, body mass index (BMI), waist circumference (WC) and neck circumference (NC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), HDL-cholesterol (HDL), triglycerides (TG) and fasting blood glucose (FBG), for the classification of MetS, the criterion of the International Diabetes Federation (IDF) was used. The present study is approved by the research ethics committee, according to the opinion no CAEE: 2.781.461.

Results:
The prevalence of MetS was 39% (n = 48) in the sample evaluated, the group with MetS had the highest mean / median of the variables age (42.8 years; p = 0.012), BMI (29 kg/m
2
; p <0.001), NC (35 cm; p <0.001), SBP (130 mmHg; p <0.001), DBP (89 mmHg; p <0.001), CT (186 mg/dL; p <0.001) and TG (157 mg/dL; p <0.001) compared to the group without MetS, moreover 58.15% (n = 82) of the individuals in the group with MetS were overweight.

Conclusions:
There was a high prevalence of MetS in the sample evaluated, in addition to risk factors. Patients on ART can demonstrate metabolic changes such as dyslipidemia, atherosclerosis, among others, so it is essential to prevent and control the presence of risk factors in order to avoid the development of chronic and consequently cardiovascular diseases.
Abstract 11290: Mechanical Loading Enhances the Ability to Predict Hypertrophic Cardiomyopathy Phenotypes with Human Induced Pluripotent Stem Cell Derived Cardiac Micro-Tissues
Authors: Guo Jingxuan , Jiang Huanzhu , Moreno Jonathan , Bhagavan Druv , Li Allie , Damiano Ralph , Silva Jonathan R , Cresci Sharon , Huebsch Nathaniel
Published: March 2022

Introduction:
Modeling hypertrophic cardiomyopathy (HCM) with human induced pluripotent stem cell (hiPSC) derived cardiomyocytes is challenging because of the immaturity of hiPSC-derived cardiomyocytes along with the need to recapitulate non-genetic factors that contribute to HCM pathogenesis. We assessed the effects of mechanical loading on the action potential waveform morphology of hiPSC-derived micro-heart muscle. We benchmarked these results against action potential morphology measured in primary human cardiomyocytes from HCM patients.

Hypothesis:
Mechanical loading is necessary for expression of HCM phenotypes in genotype-positive hiPSC cardiomyocyte engineerd tissues

Methods:
Control and MYBPC3
+/-
iPSC were differentiated into cardiomyocytes which were used to form micro-heart muscle atop soft silicone rubber substrates with rigidity matching healthy (15 kPa) or fibrotic heart (65 kPa) muscle. Micro-tissues were stained with voltage sensitive dye to assess action potential duration (APD) under field pacing. Contractility was measured by monitoring the motion of fluorescent beads embedded into the substrates. Freshly isolated surgical specimens from HCM patients were enzymatically digested into single ventricular myocytes and compared to discarded WT donor hearts as controls. Adult cardiomyocytes were stained with the same voltage sensitive dye to measure APD.

Results:
MYBPC3
+/-
micro-tissues had similar action potential waveforms to controls when the tissues worked against a 15 kPa substrate, although the MYBPC3
+/-
tissues had higher contractility. On 65 kPa substrates, the degree of hypercontractility in MYBPC3
+/-
tissues was less substantial. However, the action potential duration (APD) of these tissues was significantly longer than controls. This increase in APD of hiPSC-cardiomyocytes with an HCM-causing mutation was consistent with an increase in APD observed in primary HCM cardiomyocytes as compared to controls.

Conclusions:
Mechanical loading may be required to induce electrophysiological aspects of HCM phenotypes in genotype-positive cells to facilitate modeling this disease with iPSC-derived heart tissues.
Abstract 11297: Longitudinal Lipidomics Profiling of Risk for Hypertension in American Indians: The Strong Heart Study
Authors: Zeng Wenjie , Miao Guanhong , Chen Mingjing , Ying Zhang , Umans Jason , Cole Shelley , Lee Elisa T , Howard Barbara , Fienhn Oliver , Zhao Jinying
Published: March 2022

Background:
Dyslipidemia is an important risk factor for hypertension (HTN). Routine clinical tests cannot capture all molecular lipid species in blood (i.e., lipidome). Moreover, a longitudinal lipidomic profiling of risk for HTN is still lacking in any racial/ethnic groups.

Objective:
Identify novel lipid species and lipidomic signatures associated with risk of HTN in American Indians, independent of traditional risk factors (TRFs).

Methods:
Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,916 fasting plasma samples from 1,958 American Indians attending two clinical examinations (~5.5 years apart) in the SHS. Elastic net was used to select baseline lipids associated with risk of HTN. Longitudinal associations between changes in lipidome and changes in blood pressure measures, e.g., SBP, DBP, mean arterial pressure (MAP), were examined by mixed-effect linear model, adjusting for TRFs and baseline lipids. Multivariate and network analysis was used to identify lipidomic signatures and differentially co-regulated lipid pairs associated with risk of HTN.

Results:
Of 905 normotensive participants at baseline, 276 developed HTN after 5-year follow-up. After adjusting for TRFs (age, age
2
, sex, center, BMI, smoking, and diabetes), higher baseline levels of 144 lipids (38 known), including glycerophospholipids, glycerolipids, acylcarnitines, sphingolipids, and fatty acids, were significantly associated with increased (HRs:1.03- 2.07) or decreased (HRs: 0.80 - 0.94) risk of HTN. A lipid score comprising 38 baseline lipids significantly improved risk prediction beyond TRFs (ROC increases from 0.678 to 0.725, P<0.001). Longitudinal change in plasma lipidome explains up to 3.2% variability in changes of BP measures. Multivariate and network analysis identified lipidomic signatures and differentially regulated lipid networks associated with risk of HTN.

Conclusion:
We identified novel molecular lipids and lipidomic signatures associated with risk of HTN, independent of TRFs. If replicated, the newly identified molecular lipids may serve as novel biomarkers for risk stratification and provide therapeutic targets for early intervention tailored to American Indians.
Abstract 11298: Tablet-Based Echocardiography is a Valuable Tool to Effectively Evaluate Patients with Sars-Cov-2 While Limiting Sonographer Exposure
Authors: Leone David M , Ghiroli Stephen , Karnik Ruchika , Faherty Erin , Ferdman Dina
Published: March 2022

Background:
The SARS-Cov-2 virus and the associated Multi-System Inflammatory Syndrome in Children (MIS-C) can cause myocardial injury, cardiac dysfunction, and coronary dilation. This makes echocardiography a key component during clinical evaluation. To improve technician safety, we implemented a protocol utilizing a tablet-based echocardiography (TBE) system to evaluate patients who had active COVID-19 or whose testing was pending. We hypothesized that appropriate clinical evaluations could be completed with TBE while having a shorter exposure time for personnel.

Methods:
We retrospectively evaluated 35 patients at a tertiary, pediatric hospital between March 2020 and May 2021 who underwent TBE. We compared the TBE findings and duration to comprehensive echocardiograms done on average two weeks later with a traditional machine. A complete study included evaluation of ventricular function, coronary artery diameter, and pericardial fluid assessment. Pro-brain natriuretic peptide (pro-BNP) and troponin-T levels were reviewed. Subjects were divided into two groups based on an elevation in troponin-T as a surrogate for myocardial injury (Trop
+
and Trop
-
).

Results:
Eight subjects had cardiac dysfunction with 6/12 being from the Trop
+
group and 2/23 in the Trop
-
group. The mean troponin-T elevation was 0.32 ng/mL. Pro-BNP levels were elevated in all but 1 of the 35 subjects but were ten times higher in the trop
+
group (mean 18,055 vs 1,888 pg/mL; p = 0.001). Three subjects with MIS-C had coronary dilation noted by TBE (2 in Trop
+
and 1 in Trop
-
) with one persistently dilated at follow up. TBE findings such as coronary dilation or cardiac dysfunction guided medical therapies and no clinically relevant findings were missed when compared to studies at follow up. TBE was on average 29 minutes shorter (41 ± 18 vs 12 ± 5 min; p < 0.001). One patent ductus arteriosus was found by TBE and this was confirmed on repeat imaging.

Conclusions:
TBE allows for experienced sonographers to limit exposure time to potentially contagious patients and easier decontamination while not compromising essential clinical information. This study shows TBE is a useful tool to effectively evaluate patients during highly contagious viral respiratory outbreaks.
Abstract 11299: Ablation of Persistent Atrial Fibrillation Abolishes Fibrotic Substrate for Rotors Perpetuation but Creates Substrate for Macro-Reentrant Flutter: Insights from Patient-Specific Computational Modeling
Authors: Bifulco Savannah , Macheret Fima , Scott Griffin , Akoum Nazem W , Boyle Patrick M
Published: March 2022

Introduction:
Arrhythmia recurrence after ablation in persistent AF (PsAF) is common, often presenting as atrial flutter (AFL). Fibrotic remodeling is known to exacerbate arrhythmic activity in PsAF and can play a key role in sustaining rotors, but the synergy between non-conductive ablation-induced scar and native fibrosis is poorly understood.

Hypothesis:
We used computational simulations in left atrial models reconstructed from late gadolinium enhanced (LGE)-MRI to test the hypothesis that ablation in PsAF abolishes fibrotic substrate for rotor perpetuation, but also creates new substrate conducive to macro-reentrant AFL (MRs).

Methods:
LGE-MRI was performed on 24 PsAF patients pre- and 3-6 months post-ablation. Post-ablation scar was mapped into pre-ablation models (Fig A). A standardized approach was used to test inducibility. Arrhythmia episodes were classified as MR (i.e., conduction around vein, lesion, or mitral valve) or rotor-driven (i.e., rotational sources localized to compact areas of fibrotic substrate). Summary data are presented as median[IQR].

Results:
For many 13/24 pre-ablation models in which induced arrhythmias were predominantly rotor-driven, activity in the corresponding post-ablation models was primarily sustained by MR (Fig B; left and right panels, respectively). There were significantly more unique rotor sites in pre- vs. post-ablation models (Fig C, P<0.05; 1[2] vs. 0[1]) in contrast, we saw significantly more episodes of MR in post- vs. pre-ablation models (Fig D, P<0.01; 1[0.5] vs. 1[1]).

Conclusions:
In this modeling study, pre-ablation arrhythmias sustained by native fibrosis alone were more likely to be rotor-driven. In contrast, MRs were more common in models incorporating both scar from ablation and residual fibrosis. This suggests PsAF ablation may transform substrate that favors rotor perpetuation into one that is more conducive to AFL. Comparing these findings to recurrence outcomes is a crucial next step.
Abstract 11304: Association Between Somatic and Mental Health Chronic Conditions with Major Adverse Cardiac Events in Patients Enrolled in Cardiac Rehabilitation
Authors: Chacin Suarez Audry , Medina-inojosa Jose , Chamberlain Alanna M , Bonikowske Amanda R , Olson Thomas P
Published: March 2022

Introduction:
The presence of chronic somatic and mental health conditions is complex and challenging for patients and the health care system due to the health deficit accumulation, worsening outcomes, and increased health care utilization. While previous studies on multimorbidity have focused on somatic chronic conditions, we aim to assess the relation between somatic, mental, and combined somatic-mental multimorbidity (SMM) and impact on Major Adverse Cardiac Events (MACE) in patients enrolled in phase II outpatient cardiac rehabilitation (CR).

Methods:
Using the Rochester Epidemiology Project records-linkage system, we identified patients from Olmsted County, Minnesota who were 18 years old and attended (≥1) CR sessions at Mayo Clinic Rochester. The prevalence of 18 (somatic=13; mental=5) chronic conditions defined by the US Department of Health and Human Services was ascertained electronically.

Results:
We included 618 patients; 24.4% were female. Patients were 61.5±11.0 years old with 38.0% ≥65 years old. Overall median number of chronic conditions was 6 (Range 0-13) with 98.8% of patients having ≥2 conditions. The prevalence of combined SMM was 44.6%. Mean follow-up was 7.3± 4.5 years, 147 (23.7%) patients had MACE (number): acute coronary syndrome (46), percutaneous coronary intervention (33), heart failure (16), stroke (8), coronary artery bypass grafting (4), ventricular arrhythmias (4), or death (65). Risk of MACE in patients with SMM was significantly higher compared to patients with only somatic conditions (HR: 1.62, 95% CI: 1.14-2.30,
p=0.01
),
Figure 1.
The association remained significant after adjustment for age and sex (
p=0.006
).

Conclusions:
Our results show that somatic-mental multimorbidity (SMM) in CR patients is highly prevalent and imposes a higher risk of MACE compared with patients who have only somatic conditions highlighting the importance of individualized assessment and care plans to reduce adverse events and mortality.
Abstract 11314:
Trpm2
Deletion Alleviates Atherosclerosis by Inhibiting the Activation of CD36 in Macrophages
Authors: Zong Pengyu , Feng Jianlin , Yue Zhichao , Yu Albert S , Yue Lixia
Published: March 2022

Introduction:
Atherosclerosis and its complications are the leading cause of death. The central pathological features of atherosclerosis are macrophage infiltration and foam cell formation, in which CD36 is crucial in activating macrophages and mediating the uptake of cholesterol. However, mechanisms regulating the activation of CD36 remain unclear. TRPM2 is an Ca
2+
permeable channel activated by oxidative stress, which occurs in the activation of macrophages.

Hypothesis:
We hypothesized that during atherosclerosis, TRPM2 is critical for the activation of CD36 in macrophages. Thus,
Trpm2
deletion inhibits macrophage activation and foam cell formation.

Methods:
ApoE
-/-
mice and
ApoE
-/-
mice with
Trpm2
deletion were fed with high-fat food to induce atherosclerosis. Oil red O and immunofluorescence staining were performed to evaluate lipid deposition and macrophage load in aorta. Transwell assay was used to test macrophage infiltration and emigration. Oxidized LDL (oxLDL) or thrombospondin-1 (TSP1) was used to activate CD36. Western blot was used to examine the activation of CD36 signaling. ROS and Ca
2+
imaging were performed to examine the activation of macrophages by CD36.

Results:
Trpm2
deletion: (1) reduced lesion ratio (0.13 ± 0.02 vs 0.36 ± 0.02) and macrophage load (20.93 ± 4.82 / mm
2
vs 60.20 ± 8.36 / mm
2
) in aorta; (2) inhibited oxLDL uptake (32.24 ± 7.65 % vs 100 %) by macrophages; (3) suppressed macrophage infiltration (15.83 ± 2.44 / mm
2
vs 46.83 ± 4.62 / mm
2
) and preserved macrophage emigration (15.5 ± 1.73 / mm
2
vs 5.0 ± 0.73 / mm
2
); (4) inhibited ROS production (5.32 ± 0.61 % vs 28.82 ± 1.48 %) and increase of intracellular Ca
2+
(2.92 ± 0.86 % vs 11.95 ± 1.60 %) in macrophages induced by oxLDL (n= 6 ~ 8 for all data). Also, oxLDL and TSP1 activated TRPM2 via CD36, and TRPM2 was required for the activation of CD36 signaling in macrophages by oxLDL or TSP1.

Conclusions:
In summary, TRPM2 and CD36 activated each other in macrophages, which promoted the development of atherosclerosis.
Abstract 11333: Muscle Specific MicroRNA-499-5p Impairs Angiogenesis in Ischemic Hindlimb of Diabetic Micehindlimb of Diabetic Mice
Authors: Cheng Zhongjian , Truongcao May , Wang Chunlin , Gonzalez Carolina , Huang Grace , Cimini Maria , Mallaredy Vandana , Lucchese Anna M , Benedict Cindy , Ibetti jessica , Garikipati Venkata , Verma Suresh K , Koch Walter J , Kishore Raj
Published: March 2022

Introduction:
Limb ischemia is one of the most prevalent cardiovascular complications in diabetic patients. The underlying mechanisms remain incompletely understood. Previously, we have reported that microvascular endothelial cells (MVECs) play an important role in angiogenesis. Recent study demonstrated that skeletal muscle cells (SKMCs) regulate angiogenesis process via paracrine signals; level of miR-499, a muscle specific miR, was enhanced in diabetic hearts/cardiomyocytes and overexpression of miR-499 impaired MVEC function. We observed that level of miR-499-5p, but not -3p, was increased in skeletal muscle cells (SKMCs), MVECs and SKMC-derived extracellular vehicles (SKMC-EVs) in db/db mice.

Hypothesis:
SKMC-EVs-derived miR-499-5p impairs MVEC function in diabetes.

Methods:
MVECs and SKMCs, and SKMC-EVs were isolated from 8-10-week male db/+ and db/db mice. Ischemic hind limb (IHL) surgery was conducted in 8-10-week male wildtype C57BL/6J, diabetic db/db and non-diabetic db/+ mice.

Results:
Level of miR-499-5p was increased in SKMCs and MVECs from db/db mice. Overexpression of miR-499-5p impaired tube formation and migratory activity of MVECs. Intramuscular injection of anti-miR-499-5p lentivirus ameliorated blood perfusion and capillary density in IHL of db/db mice. Mechanistically, miR-499-5p level was increased in diabetic SKMC-EVs. Inhibition of EV formation/section by GW4869 ameliorated diabetic SKMCs-enhanced miR-499-5p level in MVECs. Local injection of diabetic SKMC-EVs impaired blood perfusion and capillary density in C57BL/6J mice. Moreover, diabetic SKMC-EVs-impaired tube formation and migratory activity of MVECs was ameliorated by silencing of miR-499-5p in the diabetic SKMCs ameliorated. Level of sex-determining region Y-box 6 (SOX6), the most attractive gene targeted by miR-499-5p, was decreased in MVECs of db/db mice. Finally, silencing of SOX6 impaired tube formation, migration and pro-angiogenic factor secretion from MVECs.

Conclusions:
miR-499-5p impairs angiogenic property of MVECs in diabetic mice via SKMC-EV/miR-499-5p/SOX6/proangiogenic factors cascades. miR-499-5p and SOX6 may be novel targets for prevention/therapeutics of ischemic limb injury in diabetic patients.
Abstract 11345: Incidence, Characteristics, and Outcomes of Patients Presenting to an Urban Academic Institution with ST-Segment Elevation Myocardial Infarction During the COVID-19 Pandemic
Authors: Taylor Eric , Bidwell Katrina , Tharp Peyton , Cook Daniel , Blaker Noah , Nielsen Chris , Fernandes VALERIAN
Published: March 2022

Introduction:
ST-segment elevation myocardial infarction (STEMI) is an emergency presentation of an acutely occluded coronary artery. Following the announcement of the COVID-19 pandemic (March 11, 2020), a global decrease in STEMI incidence has been observed. Incidence, characteristics, and outcomes for STEMI activation patients were investigated in the 5 years prior (“reference period”) to and 1 year into the pandemic (“pandemic period”). We assessed the hypothesis that pandemic period STEMI activations will have more severe infarction (elevated troponin I), a higher percentage of true STEMI, and worse outcomes (higher case fatality rate).

Methods:
STEMI activation incidence was obtained from an institutional database (reference period n = 430; pandemic period n = 31). Patient characteristics and outcomes were obtained retrospectively from electronic health records (EHRs). True STEMI was adjudicated based on chest pain, EKG, troponins, and angiogram.

Results:
Monthly STEMI activations declined significantly in the first year of the pandemic (2.50 ± .68 vs. 7.17 ± .41,
P
= <.001). No significant difference in demographic characteristics (age, BMI, and male-to-female ratio) were observed. True STEMI percentage was higher during the pandemic (80.65% vs. 70.93%), but not statistically significant. Peak troponin levels for true STEMI were significantly higher during the pandemic (98.83 ± 25.82 vs. 51.44 ± 4.11,
P
= .003). There was no significant difference in 30-day and 90-day case fatality rates.

Conclusions:
STEMI activation incidence declined significantly during the pandemic; interestingly, the proportion of these which were true STEMIs remained consistent. True STEMIs during the pandemic had higher troponin levels suggesting larger infarct, but there was no significant difference in case fatality. In conclusion, fewer patients presented with STEMI while case fatality remained unchanged despite more severe infarct occurrence during the pandemic.