bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16343: Sarpogrelate, a Selective Serotonin
2a
Receptor Antagonist, Suppresses Pressure Overlaod-induced Cardiac Hypertrophy and Systolic Dysfunction Through Inhibiting Erk1/2/gata4 Pathway
Authors: Shimizu Kana , Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Miyazaki Yusuke , Murai Noriyuki , Honda Hiroki , Kawakami Yoshiki , Shimizu Satoshi , sari nurmila , Wada Hiromichi , Hasegawa Koji , Morimoto Tatsuya
Published: November 2020

Introduction:
Serotonin (5-HT), a neurohormone involved in a wide range of physiological functions, has generated much interest in recent years regarding its potential role in cardiac function. It is reported that sarpogrelate, a selective 5-HT2A receptor antagonist, possesses cardioprotective effect against myocardial infarction, however, the precise molecular mechanism of the effect is still unclear. In this study, we examined the effect of sarpogrelate on pressure overload-induced development of heart failure, another heart failure model.

Methods:
First, primary cultured cardiomyocytes were treated with 1 μM sarpogrelate and then stimulated with various hypertrophic stimuli. Cardiomyocytes were stained with anti-actinin antibody and the surface area of the cells were measured. The phosphorylation levels of ERK1/2 and GATA4 were assessed by western blotting. Next, C57BL/6j male mice were subjected to a transverse aortic constriction (TAC) and sham operation. One day after the operation, the mice were randomly divided into 3 groups: sarpogrelate at 1 mg/kg or 5 mg/kg, and vehicle as a control. Daily oral administration was repeated for 8 weeks.

Results:
Sarpogrelate significantly suppressed an increase in the surface area of cardiomyocytes induced not only by 5-HT, but also by phenylephrine, angiotensin II and ET-1. Sarpogrelate suppressed phenylephrine-induced phosphorylation of ERK1/2 and GATA4. In a mice model of heart failure, echocardiographic analysis showed that 5 mg/kg sarpogrelate significantly prevented a TAC-induced increase in posterior left ventricular wall thickness and a decrease in fractional shortening at 8 weeks after the operation. One mg/kg sarpogrelate also suppressed TAC-induced increase in HW/BW ratio, myocardial cell diameter and the mRNA levels of ANF and BNP. Moreover, 1 mg/kg sarpogrelate significantly suppressed TAC-induced phosphorylation of ERK1/2.

Conclusions:
These results indicate that sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2/GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy.
Abstract 16364: Effect of Social Determinants on Outcomes in a High-risk Cardio-obstetrics Population
Authors: Carland Corinne , Panelli Danielle , Lee Christine , Sherwin Elizabeth , Levin Eleanor , Zarafshar Shirin , Tremmel Jennifer A , Tsai Sandra , Bianco Katherine , Khandelwal Abha
Published: November 2020

Introduction:
Cardiovascular disease is the leading cause of maternal mortality. The hemodynamic changes that occur during pregnancy make this a particularly vulnerable time for women with heart disease. Additionally, it is known that social determinants have an effect on certain outcomes in pregnancy, although research to quantify this effect is limited. We compared demographics and outcomes for women in upper- and lower-income brackets based on zip codes.

Methods:
We performed a retrospective cohort study of high-risk pregnant patients with cardiac diagnoses between November 2010 and June 2019. Patients were stratified into upper- and lower-income based on median household income in their zip code (2018 U.S. census).

Results:
We studied 191 pregnancies. Patients were stratified by zip code into lower (<$118,201/yr, N = 95) and upper median household income (N = 96) groups (Table 1). Women in the lower income bracket had more antepartum hospitalizations (38.3% vs 17.9%), were younger (30.6 vs 33.9 years), Hispanic (42.1% vs 10.4%), and more likely to have public insurance (46.8% vs 21.3%). There was a difference in cardiac diagnoses between the two groups; those with lower income had more structural heart disease (41.1% vs 17.7%) and fewer arrhythmias (25.3% vs 39.6%). In the lower income group, there were 2 maternal deaths and 1 neonatal death before discharge, while in the upper income there was 1 neonatal death.

Conclusions:
Our study examined the relationship between median income per zip code and pregnancy outcomes, and demographics in women with heart disease. Our observations demonstrate a significant difference in maternal age, race, distribution of cardiac diagnoses, and antepartum hospitalizations. Despite all women being treated at the same facility, antepartum hospitalizations differed based on income bracket. Social determinants of health are important factors that impact outcomes in the cardiac-obstetric population and require further investigation.
Abstract 16371: Clinical Outcomes of Early Ventricular Arrhythmias and Severe Right Ventricular Failure After Left Ventricular Assist Device Implantation
Authors: Seok Kieun , Lee Dae Hyun , Vautier Richard A , Hawk Fahad , Kulkarni Deepika , Lu Yuan Yuan , Mackie Benjamin , Restrepo-Jaramillo Ricardo , Stachura Zachary , Oliveira Guilherme , Prida Xavier , Feliberti Jason , Cassidy Dennis , Herweg Bengt
Published: November 2020

Introduction:
Right ventricular failure (RVF) and ventricular tachyarrhythmias (VA) are common causes of poor outcome and mortality in patients with left ventricular assist device (LVAD). VA can precipitate RVF and inotropic therapy can further exacerbate VA. The purpose of this observational study was to investigate the individual and combined impact of RVF and VA on mortality in the early postoperative period after LVAD.

Methods:
We performed a retrospective analysis of patients undergoing implantation of an LVAD between 2014 to 2017 (N=110). Telemetry tracings and device interrogations were reviewed. Early VA was defined as any ventricular tachycardia and ventricular fibrillation within the first month after LVAD associated with hemodynamic compromise that required device therapy, catheter ablation, and/or antiarrhythmic therapy. Kaplan-Meier statistics with the Mantel-Cox log-rank test was used to analyze survival.

Results:
We identified 110 LVAD patients, age 57±13 years, 80 males (73%), ischemic cardiomyopathy n=54 (49%), (HeartWare (n=44), HeartMate II (n=44), and HeartMate III (n=22)). Patients were categorized into group A - early VA and severe RVF (n=14); group B - early VA without RVF (n=16); group C - severe RVF without early VA (n=33); and group D - neither VA nor RVF (n=47). The 1-year survival of group A, B, C, and D was 50%, 69%, 73%, and 89%, respectively (p=0.001 comparing each group to the other groups, enclosed figure). The presence of early VA did not relate to RVF (p=0.7). Pre-operative VA was related to post-LVAD VA (RR 9.4, p=0.003).

Conclusions:
Patients without early VA or severe RVF demonstrated the best survival. Both, VA and severe RVF decreased survival. The presence of both, VA and RVF appears to potentiate mortality. Pre-operative VA is related to post-LVAD VA. These data raise the question if intra-operative ablative therapy in patients undergoing LVAD implantation could improve post-operative mortality, VA, and RVF.
Abstract 16380: Disease Specific Induced Pluripotent Stem Cell Derived Cardiomyocytes Represent Pathophysiological Phenotype in Hypertrophic Cardiomyopathy
Authors: Takeda Maki , Miyagawa Shigeru , Kawamura Takuji , Ito Emiko , Harada Akima , Mochizuki-oda Noriko , Sawa Yoshiki
Published: November 2020

Although hypertrophic cardiomyopathy (HCM) is a major hereditary heart disease, unknown underlying basic pathology make it difficult for physicians to heal this disease. We hypothesized that the disease specific iPS derived cardiomyocytes from HCM with the myosin binding protein C (MYBPC3) mutation represent the pathophysiological phenotype, and editing the mutation would cancel the diseased phenotype to check the role in the mutation gene. We established iPS cells with heterozygous frameshift mutation (WT/MT-iPS) from patient and performed genome editing to generate cells with repair of mutation (WT/WT-iPS) and homozygous mutation (MT/MT-iPS) using CRISPER-Cas9. Droplet digital PCR revealed that the transcript of the mutant allele was about 30% in WT/MT-iPS derived cardiomyocytes (CMs) compared to the WT allele and also WT/WT-iPSCMs and MT/MT-iPSCMs expressed only the transcript of WT allele and MT allele, respectively. The RNA expression of MYBPC3 was restored in WT/WT-iPSCMs and decreased in MT/MT-iPSCMs assessed by quantitative real-time PCR. Sarcomeric disarray was observed in WT/MT-iPSCMs, and was more prominently expressed in MT/MT-iPSCMs assessed by immunofluorescence staining. Cell motion analyzer revealed that relaxation velocity was significantly decreased and relaxation duration was significantly increased in WT/MT-iPSCMs and MT/MT-iPSCMs compared to WT/WT-iPSCMs. Moreover significant increase in contraction end velocity was observed in MT/MT-iPSCMs compared to WT/MT and WT/WT-iPSCMs. Established disease specific iPS-CMs with MYBPC3 mutation reproduces pathophysiology in HCM, providing important clues that elucidate true nature in patient’s hereditary diseases.
Abstract 16704: Leukocyte Telomere Length and Risk of Stroke: The Strong Heart Family Study
Authors: Goode Caroline , Zhao Jinying , Devereux Richard B , Murthy Santosh , Merkler Alexander E , Singh Parmanand , Umans Jason G , Howard Barbara V , Cole Shelley , Fretts Amanda M , Best Lyle G , Ali Tauqeer , Lee Elisa T , Stoner Julie , Zhang Ying
Published: November 2020

Introduction:
Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We
hypothesized
that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS).

Methods:
The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension.

Results:
Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0).

Conclusions:
In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.
Abstract 16722: Perinexal Width Modulates Sodium Channel Recruitment During Extracellular Stimulation
Authors: Colucci Chang Katrina , Wu Xiaobo , Blair Grace , Lozano Alicia , Hanlon Alexandra , Poelzing Steven
Published: November 2020

Excitability in cardiomyocytes is dependent on the subthreshold current required to raise transmembrane potential to the activation threshold of voltage gated sodium channels and sodium channel recruitment to trigger an action potential. Cardiac sodium channels are densely expressed in the intercalated disc within the perinexal nanodomain, which is 2 orders of magnitude narrower than bulk extracellular interstitium. We hypothesized that perinexal narrowing reduces extracellular induced excitability because the perinexus functions as a voltage divider.

Methods:
Excitability with an extracellular stimulus was quantified in isolated Langendorff perfused male retired breeder guinea pig hearts by strength duration curves using the Lapicque method. Interventions included changing extracellular potassium (K+: 3, 4.5, and 10 mM), inhibiting sodium channels (90-uM Flecainide), and narrowing the perinexus by increasing extracellular calcium (Ca2+: 1.25 to 2.5 mM).

Results:
Consistent with previous studies, decreasing K+ from 4.56 to 3 mM depressed excitability with 2.5 mM Ca2+ but not 1.25 mM Ca2+, and conduction velocity (CV) decreased by 10.5 % with both 1.25 and 2.5 mM Ca2+. When K+ was raised from 4.56 to 10 mM, no change was seen in excitability with both Ca2+ concentrations. However, CV decreased by 16% with both Ca2+ concentrations. Flecainide depressed excitability only with 2.5 but not 1.25 mM Ca2+. Meanwhile CV decreased by 13% with 1.25 but CV did not change with 2.5 mM Ca2+. Finally, raising Ca2+ alone at baseline decreased excitability, without substantially changing conduction.

Conclusions:
Elevating extracellular calcium to narrow perinexi reduces excitability measured by extracellular stimulation consistent with a hypothesis that sodium channels in the intercalated disc are electrically isolated from the bulk interstitium. Furthermore, excitability and conduction do not correlate in response to similar K+ changes when Ca2+ also varies, suggesting cardiac excitability and propagation are independent mechanisms when the excitatory current occurs through regenerative propagation as occurs through gap junctions or arrives via an extracellular field as occurs with pacing and ephaptic coupling.
Abstract 16732: Medical Malpractice Claims and Percutaneous Coronary Intervention Mortality Among Interventional Cardiologists - Evidence From New York
Authors: Arora Vishal S , Yeh Robert W , Shen Changyu , Wadhera Rishi
Published: November 2020

Introduction:
The medical malpractice liability system aims to identify poorly performing providers and improve the quality and safety of health care by deterring negligence, but there is concern that the current system may not accomplish these objectives. We evaluated whether interventional cardiologists who previously lost or settled a malpractice lawsuit had higher risk-adjusted mortality rates (RAMR) for percutaneous coronary intervention (PCI) in New York State.

Methods:
We used the Physician Profile website to identify information on demographics as well as lost or settled malpractice lawsuits for interventional cardiologists in New York State between 2010 and 2016. Publicly reported data from the New York State Department of Health was used to determine RAMR for interventional cardiologists who performed PCIs between 2014 and 2016. We then fit a multivariable linear regression model to examine the association between a prior lost or settled malpractice lawsuit and RAMR among interventional cardiologists, adjusted for years in practice, domestic vs. foreign medical graduate, and case volume.

Results:
We identified 201 interventional cardiologists in New York State between 2014-2016, of whom 16 (8.0%) had lost or settled a malpractice lawsuit. Those with these prior malpractice lawsuits were more likely to be male (100%), domestic graduates (62.5%), spent more years on average [Standard Deviation] in clinical practice (28.8 [9.3] vs. 20.9 [11.2]), and had higher average case volumes (557.0 [290.1] vs. 386.0 [302.1]). After multivariable adjustment, interventional cardiologists with a prior lost or settled malpractice lawsuit had similar RAMRs than those without such a lawsuit (difference: -0.02%, 95% confidence interval -0.47% to +0.42%).

Conclusions:
We found no relationship between having lost or settled a prior malpractice lawsuit and PCI mortality rates among interventional cardiologists in New York State. These findings raise the possibility that prior malpractice claims do not reliably identify poor-performing providers.
Abstract 16737: Inhibition of Tgf-β1 Signaling Protect Against Cell-Cell Decoupling and Asynchronous Automaticity of Tbx18-ipms
Authors: Fan Jinqi , Kim Nam Kyun , Fernandez Natasha , Shin Minji , Cho Hee
Published: November 2020

Background:
We have previously demonstrated that TBX18 suffices to reprogram postnatal ventricular cardiomyocytes to induced pacemaker cells (TBX18-iPMs). However, the nascent automaticity appeared to wane over time, characterized by loss of syncytial pacing but preservation of single cell automaticity.

Hypothesis:
Based on increase in Tgfβ ligands in TBX18-iPMs and the known role of Tgfβ signaling in electrical remodeling, we hypothesized that loss of syncytial automaticity is due to electrical decoupling of the iPMs mediated by Tgfβ signaling.

Methods:
Adenoviral vectors expressing either human TBX18 or GFP were used for gene transfer into neonatal rat ventricular myocytes (NRVMs) or adult rat ventricular myocardium in vivo.

Results:
NRVM monolayers transduced with GFP were mostly quiescent, interspersed by paroxysmal contractions. In contrast, TBX18 transduced NRVM monolayers showed spontaneous and rhythmic contractions, but the syncytial pacing wavered over the next 5-7 days although numerous iPMs continued to beat asynchronously. Treatment of TBX18-iPMs with an inhibitor of Tgfβ receptors, A83-01, preserved syncytial pacing, suggesting that electrical remodeling cues from Tgfβ signaling led to loss of iPM-iPM electrical coupling. We examined the molecules that are integral to the function of gap junction in the myocardium, namely Cx43, N-cadherin and β-catenin. Cx43 and N-cadherin were downregulated in TBX18-iPMs compared to control by 77±16% and 43±11% (p<0.01, n=6), respectively. Total β-catenin protein level was unaltered, but its distribution decreased at the sarcolemmal and increased in the nuclei of TBX18-iPMs compared to control. Inhibition of Tgfβ with A83-01 restored Cx43 protein level in TBX18-iPMs (2.2-folds higher) compared to untreated TBX18-iPMs. Similarly, adult rats that received intramyocardial injection of TBX18 showed increased Cx43 expression at the boundary between the iPMs and the host myocardium when the animals were treated with systemic delivery of A83-01 for one week compared to TBX18 animals treated with DMSO.

Conclusions:
TBX18 activates Tgfβ signaling which suppresses cell-cell electrical coupling. Inhibition of Tgfβ signaling in TBX18-iPMs preserves gap junction components and syncytial pacing.
Abstract 16740: Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (mesa)
Authors: Echouffo Tcheugui Justin B , Ogunmoroti Oluseye , Golden Sherita H , Bertoni Alain G , Mongraw-chaffin Morgana , Pandey Ambarish , Ndumele Chiadi E , Michos Erin D
Published: November 2020

Introduction:
Markers of glucose dysregulation and insulin resistance (hemoglobin A
1C
[HbA
1C
], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance [HOMA-IR], and fasting insulin) capture various metabolic pathways, and thus could be differentially associated with heart failure (HF) subtypes (HF with preserved ejection fraction [HFpEF] or HF with reduced ejection fraction [HFrEF]). There are limited data on such associations.

Hypothesis:
Glycemic markers differentially relate to HFpEF and HFrEF.

Methods:
We included 6,688 (39% white, 28% black, 12% Chinese, and 22% Hispanic) adults without prevalent cardiovascular disease who attended the first MESA visit (2000-2002). Participants were followed for incident hospitalized HF, adjudicated for HFpEF or HFrEF [EF ≥50% vs. <50%]. Estimates of the association of each glycemic markers (HbA
1C
, FPG, HOMA-IR, and fasting insulin) and glycemic status (normoglycemia, prediabetes, diabetes) with HF and each of its subtypes (HFpEF vs. HFrEF) were evaluated using adjusted Cox models.

Results:
The mean age of participants was 62 ± 10 years, with 53% women. There were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events) over a median follow-up of 15 years.
Table
shows the estimates of the associations of glycemic makers and HF subtypes. Diabetes status conferred higher risks of HFpEF and HFrEF of similar magnitude compared to normoglycemia (all
P
<0.001). Similarly, higher levels of HbA
1C
(≥6.5%) and FPG (
≥
126 mg/dL) were each associated with higher risks of HFpEF and HFrEF (all
P
<0.001), to a comparable extent for each HF subtype. Prediabetic range HbA
1C
(5.7-6.4%) or FPG (100-125 mg/dL), as well as HOMA-IR and fasting insulin were not-significantly associated with HFpEF or HFrEF.

Conclusions:
Among community-dwelling individuals, HbA
1C
and FPG in the diabetes range were each positively associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.
Abstract 16749: Prevalence, Predictors, and Prognostic Implications of Left Ventricular Systolic Dysfunction Among Patients With STEMI in India: The Prospective NORIN-STEMI Registry
Authors: Pandey Ambarish , Rao Shreya , MP Girish , Gupta Puneet , Arora Sameer , Hendrickson Michael , Qamar Arman , BANSAL ANKIT , Batra Vishal , Mehta Vimal , Yusuf Jamal , Kathuria Sanjeev , Vaduganathan Muthiah , Bhatt Deepak L , Gupta Mohit
Published: November 2020

Introduction:
Left ventricular (LV) systolic dysfunction (LVSD) and HF are important complications of ST-elevation myocardial infarction (STEMI). The prevalence and prognostic implications of LVSD in patients with STEMI in low/middle-income countries such as India are not well established.

Methods:
The present analysis was performed using data from the ongoing
,
prospective NORIN-STEMI registry of patients presenting with STEMI to 2 tertiary care medical centers in New Delhi, India from January to November 2019. LV ejection fraction (EF) was assessed at STEMI presentation using transthoracic echocardiography. Covariate-adjusted logistic regression models were constructed to evaluate the association of LVSD (mild: EF = 40-50%; moderate/severe: EF<40%; ref: EF>50%) with risk of in-hospital and 30-day mortality.

Results:
Among 3,635 patients with STEMI (age: 55[45-62], 33%≤50 years, 16% women), 1,489 (41%) had mild and 1,675 (46%) had moderate/severe LVSD on presentation. Patients with greater LVSD more commonly presented with anterior wall STEMI and had more frequent involvement of the left anterior descending artery as the culprit vessel. Among those with no, mild or moderate/severe LVSD, PCI was performed in 70% and 62% of patients, respectively. Hypertension, prior myocardial infarction, physical inactivity, greater time since symptom onset, and lower literacy levels were each independently associated with higher likelihood of LVSD. In adjusted analysis, LVSD was significantly associated with higher likelihood of in-hospital but not 30-day mortality (
See Table
).

Conclusion:
Among patients presenting to tertiary care centers in India with STEMI, LVSD is common, with 87% demonstrating LVEF<50%. LVSD was significantly associated with higher risk of in-hospital and 30-day mortality. Future studies are needed to determine if quality improvement efforts to standardize pathways for primary PCI may lessen occurrence of LVSD.
Abstract 16758: Presence of Left Atrial Fibrosis Contributes to Aberrant Hemodynamics and Increased Risk of Stroke in Atrial Fibrillation Patients
Authors: Paliwal Nikhil , Salvador Matteo , Ohara Ryan , Ali Rheeda , Yu Rebecca , Daimee Usama A , Akhtar Tauseef , Pandey Pallavi , Spragg David D , Calkins Hugh G , Trayanova Natalia
Published: November 2020

Introduction:
Atrial fibrillation (AF) patients are at high risk of stroke, with the left atrial appendage (LAA) found to be the most common site of clot formation. Left atrial (LA) fibrosis is also associated with higher stroke risk. However, the mechanisms for increased stroke risk in patients with atrial fibrotic remodeling are poorly understood. We sought to explore these specific mechanisms using fluid dynamics analysis.

Hypothesis:
The presence of LA fibrosis leads to aberrant hemodynamics in the atria, contributing to increased stroke risk in AF patients.

Methods:
We retrospectively collected LGE-MRI images of 3 AF patients and reconstructed their 3D LA endocardial surfaces. Fibrotic regions were identified as those with intensity 3 standard deviations greater than the mean LA blood-pool intensity. Personalized computational fluid dynamic simulations were performed, and hemodynamics at the LA wall were quantified by wall shear stress (WSS, friction of blood) and oscillatory shear index (OSI, temporal directional change of WSS). For each case, WSS and OSI were compared between fibrotic and normal regions.

Results:
WSS was significantly lower in the fibrotic region as compared to normal region for all 3 cases. Additionally, OSI was higher in the fibrotic region as compared to normal region for all 3 cases. However, this different was statistically significant for cases 1 and 3; case 2 was not statistically significantly different. Low WSS and high OSI in the vicinity of the fibrotic wall suggest that local blood-flow was slow and oscillating, enabling pro-thrombotic conditions for circulating blood.

Conclusion:
LA fibrosis correlates with regions of aberrant hemodynamics, which renders it susceptible to blood thrombosis. AF patients with high LA fibrosis burden will have more pro-thrombotic regions, in addition to low flow in the LAA, providing more sites for a potential clot formation. These conditions might get exacerbated during an AF event and cause stroke.
Abstract 16763: Frailty, as Measured by the Essential Frailty Toolset, is Associated With Higher Resource Utilization in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Soliman Fady K , Volk Lindsay , Kenath Rajath , Okoh Alexis K , Chao Joshua C , Baxi Jigesh , Ikegami Hirohisa , Lemaire Anthony , Russo Mark J , Lee Leonard Y
Published: November 2020

Introduction:
Frailty is an important predictor of clinical outcomes, but its contribution to resource utilization remains understudied. This study investigates the impact of frailty on high resource utilization (HRU) in patients undergoing Coronary Artery Bypass Graft Surgery (CABG).

Methods:
We reviewed data on patients who underwent CABG at a single center between 04/2018 and 12/2019. A Frailty score (FS) was calculated using the Essential Frailty Toolset (EFT). Patients were divided into two groups: Frail (FS ≥ 3/5) & Non-Frail (FS <3/5). Baseline clinical characteristics and outcomes were compared in both groups. The primary outcome was HRU (post-operative length of stay > 7 days or readmission within 30-days). Secondary outcomes included operative time, prolonged ventilation, & direct procedure costs. Multivariable logistic regression was used to assess the effect of frailty on HRU.

Results:
The study included 740 patients of whom 18% (n=132) were frail. Compared to Non-Frail patients, Frail patients were older (66 vs. 70 yrs. P<0.001) and more likely to be high risk for operative mortality (1.3% vs. 14%, p<0.001). The incidence of HRU was 28% vs. 53%, p<0.001, in Non-Frail vs. Frail patients. Frail patients had longer operative times (272 vs. 247 mins; p<0.001), and a higher incidence of prolonged ventilation (9.9% vs. 4%; p<0.001). Median direct costs were also higher in Frail subjects ($33,434 vs. $22, 207; p<0.001). On multivariable logistic regression analysis, independent predictors of HRU were (OR: 95% C.I.) Frailty: 2.19(1.44, 3.33; p=0.003), Sex (Female): 1.66 (1.14, 2.40; p=0.008), and history of COPD: 2.32(1.53, 3.54; p<0.001).

Conclusions:
About one out of every five patients undergoing CABG was classified as frail by the EFT. Frailty was associated with higher direct costs and found to be an independent predictor of high resource utilization. Further attention is required to optimize outcomes and resource use in this vulnerable population.
Abstract 16771: Longitudinal Segmental Shape Analysis of the Remodeling Left Ventricle in Chronic Mitral Regurgitation
Authors: Corporan Daniella , Padala Muralidhar
Published: November 2020

Introduction:
Severe mitral regurgitation (MR) initiates left ventricular (LV) dilatation, but preserves systolic function. Due to preserved EF, patients are not referred for correction of their MR, and the ventricle continues to enlarge. Identifying patients at risk of heart failure, just from assessing LV size is challenging. In this study, we sought to investigate if ventricular shape and sphericity can represent the pathological remodeling process in this disease.

Methods:
Sixty adult rats (N=60) were induced with severe MR by puncturing the mitral valve leaflet with a 23G needle on the beating heart, using echo guidance (Fig.A1). Transthoracic echocardiography was performed at 2, 10, 20, and 40 weeks (n=15 rats/group) for analysis of the left ventricular shape. Fifteen healthy rats (N=15) were used as a sham group for comparison.

Results:
Severe MR was confirmed in all the rats in the MR group with a MR jet area of 40.99±9.40% (
Fig.A2
), MR volume of 119.50±32.43μl (
Fig.A3
), and pulmonary flow reversal (
Fig.A4
). None of these were observed in the control group. LV dilation was observed in MR rats compared to sham (
Fig.B
). Diastolic sphericity index, LV area, and diastolic apical area index was significantly increased at 2, 10, 20, and 40 weeks after MR compared to sham (p<0.05) (
Fig.C1-C3
). Systolic sphericity index was not significantly increased compared to sham at any time-point (
Fig.D1
). LV area was unchanged at 2 weeks, and was significantly increased at 10, 20, and 40 weeks (
Fig.D2
). Systolic apical area index was significantly increased at 2, 20, and 40 weeks compared to sham (p<0.05) (
Fig.D3
).

Conclusions:
Analysis of left ventricular shape and its longitudinal changes can help detect remodeling patterns that are not visible using traditional functional indices.
Abstract 16772: Aerobic Capacity (VO
2peak
) in Congenital Heart Disease: Prognostic Implications
Authors: Soares Andrea , Mansour Emily , Puritz Alyssa , Zhao Min , cao chao , Barger Philip , Foraker Randi E , RACETTE Susan B , Peterson Linda R
Published: November 2020

Introduction:
Cardiopulmonary exercise testing provides information about functional capacity via direct measurement of respiratory gas exchange. Whether peak oxygen consumption during exercise (VO
2peak
) is predictive of outcomes in patients with congenital heart disease is controversial.

Hypothesis:
VO
2peak
has prognostic implications for death, left ventricular assist device (LVAD) placement, and cardiac transplant in adult patients with congenital cardiac diseases.

Methods:
Congenital heart disease patients were selected from a registry of cardiac patients who completed a VO
2peak
exercise test at Washington University School of Medicine between May 1993 and October 2012. Diagnoses were verified by chart review and classified according to American Heart Association guidelines. Outcome data were verified via medical record, Social Security Death Index, or phone interview. A Cox proportional-hazard regression analysis was used to investigate the association between patient survival time and one or more predictor variables. Survival time was defined as the time elapsed between VO
2peak
test and the earliest outcome of death, heart transplant, or LVAD placement.

Results:
The sample included 149 patients (49% women, mean ± SD age of 33.4 ± 11.5 years and body mass index of 25.7 ± 5.4 kg/m
2
). Mean follow-up time was 11.8 ± 3.2 years. Mean VO
2peak
was 23.0 ± 7.3 mL/kg/min for men and 20.0 ± 6.4 mL/kg/min for women. Age was comparable between men and women in the sample. In the univariate analysis, higher VO
2peak
was associated with longer event-free survival time (HR 0.91, 95% CI 0.85-0.98, p= 0.01). In the multivariable analysis, higher VO
2peak
was shown to be protective, independent of age and sex (HR 0.90, 95% CI 0.83-0.97, p=0.004).

Conclusions:
Among patients with congenital cardiac disease, higher VO
2peak
independently predicted longer event-free survival. VO
2peak
is a valuable clinical prognostic tool for patients with congenital cardiac disease.
Abstract 16781: Ventriculo-Arterial Coupling is Associated With Death and Need for Ventricular Assist Device or Heart Transplant in Patients With Transthyretin Cardiac Amyloidosis
Authors: Abou Hassan Ossama K , Hussain Muzna , Laczay Balint , Martyn Michael , Hanna Mazen A , Cremer Paul C , Popovic Zoran B , Jaber Wael A , Collier Patrick H
Published: November 2020

Background:
Transthyretin (TTR) cardiac amyloidosis (CA) results from TTR protein deposition in the extracellular space of the heart altering cardiac chamber mechanics and efficiency. Ventriculo-arterial coupling (VAC) is calculated from 2D echo derived measurements and reflects cardiac function and efficiency. We aimed to identify whether VAC assessment at diagnosis improves current risk stratification models as a prognostic tool.

Methods:
The Amyloid Heart Disease registry at our institution was used to identify 365 TTR-CA patients. Primary outcome was mortality and advanced heart failure therapy (ventricular assist device (VAD) or heart transplant).

Results:
At a median follow up of 1.9 years, VAD, transplant or death occurred in 163 (44.7%) patients. On adjusted multivariable Cox survival analysis, the Gillmore Stage which incorporates eGFR and NTproBNP (HR=2.5, 95% CI 1.96-3.18), CAD (HR=1.50 95% CI 1.02-2.20), therapy with Tafamidis (HR=0.31, 95% CI 0.19-0.51), and VAC greater than median (>1.01) (HR=2.28 95% CI 1.57-3.29, p<0.001) were independently associated with outcome (all p<0.05) (Figure).

Conclusion:
The easily measurable and widely available echo parameter VAC provides incremental independent value in patients with TTR-CA.
Abstract 16790: Myocardial Injury is an Independent Predictor of Mortality in Patients With COVID-19
Authors: Nardin Matteo , Cao Davide , Chiarito Mauro , Nicolas Johny , Sartori Samantha , Zhang Zhongjie , Dangas George , Mehran Roxana
Published: November 2020

Introduction:
Recent reports on COVID-19 patients have shown that elevated troponin (Tn) levels on hospital admission are associated with adverse outcomes. However, no data exists on the predictive role of Tn kinetics parameters in COVID-19 patients.

Aim:
To analyze the incidence, clinical outcomes and predictors of Tn kinetics parameter, including rise/fall pattern and peak values, in a large cohort of COVID-19 hospitalized patients.

Methods:
All consecutive patients admitted to an urban tertiary-care health system between February and June 2020 with COVID-19 were included. Patients were grouped according to presence of myocardial injury defined as a high-sensitivity TnI level ≥0.1 ng/ml. A TnI level between 0.4-0.99 was defined as low positive range Tn elevation.

Results:
We included 5862 COVID-19 patients, 1558 (27%) of whom experienced myocardial injury. Advance age, male sex and higher comorbidity burden, including COPD, hypertension, CAD, atrial fibrillation, HF, CKD, and diabetes were more common in patients with myocardial injury. A total of 828/1558 (53.2%) of patients with myocardial injury died as compared to 634/4304 (14.7%) of those without (OR 6.57, 95% CI 5.76-7.48; p<0.001). After adjustment for baseline imbalances, myocardial injury remained an independent predictor of mortality (Adj.OR 5.26, 95% CI 4.57-6.05; p<0.001). Further stratification of patients into low positive range Tn elevation and myocardial injury groups showed a significant stepwise increase in mortality rates with increasing Tn values (Figure). Secondary endpoints, as shown in the Figure, occurred more frequently in patients with myocardial injury.Data on Tn kinetics parameters,such as rise/fall patterns,and associations with the outcomes will also be presented.

Conclusions:
Myocardial injury is an independent predictor of all-cause mortality in COVID-19 patients,with a stepwise increase in the risk of mortality reflecting increasing extent of myocardial damage.
Abstract 16798: Evidence of Abnormal T1 Mapping in Arrhythmic Mitral Valve Prolapse Without Significant Mitral Regurgitation
Authors: Agbor-Etang Brian B , Lim Lisa J , Ordovas Karen G , Delling Francesca N
Published: November 2020

Background:
Prior cardiac magnetic resonance (CMR) studies have reported abnormal T1 mapping, reflective of diffuse myocardial fibrosis, in patients with mitral valve prolapse (MVP) and ventricular arrhythmias. However, T1 mapping was derived from conventional Look-Locker sequences and/or obtained in selected MVP patients with severe mitral regurgitation (MR) and a clinical indication for CMR.

Hypothesis:
We hypothesize that extracellular volume (ECV) fraction, a marker of diffuse fibrosis derived from research-based, MOLLI T1 mapping sequences, is increased in MVP subjects with ventricular arrhythmias, even in the absence of significant MR.

Methods:
We performed CMRs in 10 consecutive, randomly selected MVP patients identified through our echocardiographic database, age/gender matched to 10 controls free of significant cardiac disease. All 10 MVPs underwent ambulatory EKG monitoring. CMR images were acquired using a GE 3.0T Discovery MR750w scanner. Global ECV fraction was calculated using pre- and 10 minutes post-contrast T1 times after administration of 0.1 mmol/kg of gadobutrol (Gadavist). Late gadolinium enhancement (LGE) was also obtained. MR fraction was quantified by velocity encoded CMR. Mild MR was defined as MR fraction < 16%.

Results:
MVP patients had significantly higher ECV fraction compared to controls (mean ECV (%) 32 ± 4 vs 20 ± 6, p = 0.0002), with 5/10 demonstrating non-sustained VT on ambulatory EKG monitoring. The majority (9/10 or 90%) of MVPs had mild or no MR (MR fraction < 16%), and 1/10 or 10% had moderate MR (MR fraction 18%). Only one individual in the MVP group had late gadolinium enhancement (LGE) in the papillary muscles.

Conclusion:
MVP with ventricular arrhythmias is associated with increased global ECV reflective of diffuse myocardial fibrosis, even in the absence of significant MR or LGE. Our preliminary findings highlight for the first time a primary interstitial derangement in MVP. Larger studies are needed to understand the mechanisms and prognostic significance of primary diffuse fibrosis in MVP.
Abstract 16799: Left Ventricular Hypertrophy in South African Adults and Children
Authors: Kolkenbeck Ruh Andrea , Soepnel Larske , Norris Shane , Davies Justine , Naidoo Sanushka , Ware Lisa
Published: November 2020

Introduction:
Left ventricular hypertrophy (LVH) increases risk of heart failure and sudden cardiac death. Specific changes in LV geometry and relative wall thickness (RWT) may provide additional prognostic information. As routine echocardiography may not typically be available in low-resource settings, we aimed to identify the factors associated with LVH presence and LV remodelling within adults (n=108; age 29-68 years) and children (n=56; age 4-10) in an urban cohort from a historically disadvantaged township in South Africa.

Methods:
Anthropometry and blood pressure (BP) were measured in triplicate, and self-reported diabetes mellitus, previous heart disease and hypertension medication, tobacco and alcohol use were recorded. LV mass was assessed at end-diastole perpendicular to the long axis of the LV and indexed to body surface area (LVMI). Prevalence of LVH (defined as LVMI>95g/m
2
for adults and LVMI >88.9g/m
2
[95
th
percentile] for children), eccentric LVH (LVH with RWT<=0.42) and concentric LVH (LVH with RWT>0.42) and concentric remodelling (normal LVMI with RWT>0.42) was recorded. For adults, hypertension was defined as BP ≥140/90 mmHg or on medication and for children using American Academy of Paediatrics Guidelines (2019). Body mass index (BMI) was calculated as weight (kg)/height(m)
2
.

Results:
LVH prevalence was 35.2% in adults (n=38; 74% eccentric LVH; 26% concentric LVH), and 12.5% (n=7) in children, all of which were eccentric LVH. Prevalence of concentric remodelling was 16.7% (n=18) in adults and 3.6% (n=2) in children. Hypertension prevalence was 38.9% (n=42) for adults and 53.6% (n=30) for children. LVH was present in 15.4% of normotensive children and 40.9% of normotensive adults. Multivariate logistic regression with age, BMI, hypertension and diabetes status, previous heart disease, tobacco and alcohol use showed only current tobacco use (OR 10.60 [1.72-65.25] p=0.01) increased the odds of concentric LVH in adults.

Conclusions:
Approximately one third of adults and one in ten children had LVH, with eccentric LVH the predominant type of remodelling. Hypertension prevalence in this population was also high. This preliminary analysis supports public health efforts for tobacco cessation to impact overall cardiovascular risk.
Abstract 17100: Effects of Electronic Cigarette Solvents on Endothelial Dysfunction
Authors: Jin Lexiao , Lynch Jordan , Richardson Andre , Conklin Daniel J
Published: November 2020

Introduction:
After a decade of electronic cigarettes (E-cig) in the U.S., 3 elements remain: 1) E-cigs evolve; 2) E-cigs use propylene glycol (PG) and vegetable glycerin (VG); and, 3) uncertainty about E-cig use and CVD risk. Because all E-cigs use PG:VG, we tested for vascular effects of PG:VG-derived aerosol alone.

Methods:
Female C57BL/6 mice were exposed by inhalation (6h/d*4d) to filtered air (n=10) or to PG:VG-derived aerosol (n=10). After exposures, blood and aortas were examined for changes in: circulating immune and stem cells and platelets by flow cytometry, and vascular function by isometric myography.

Results:
PG:VG exposure significantly decreased WBC (-47±7%); increased RBC (+6±1%) and hemoglobin (+4±1%), but had no effect on circulating angiogenic cells or platelet-leukocyte aggregates. In aorta, vascular smooth muscle (VSM) function measured as aortic contractility to phenylephrine (PE) was unaltered. However, acetylcholine (ACh)-induced, endothelium-dependent relaxation was significantly decreased (air: -75.5±4.2%; PG:VG: -61.8±4.2%; P<0.05), whereas sensitivity of ACh-induced relaxation was variably depressed (air EC
50
: 166±54nM; PG:VG EC
50
: 1020±435nM; 0.05<P<0.10). Because loss of ACh-induced relaxation may reflect VSM desensitization to NO, we measured relaxation of NO donor, sodium nitroprusside (SNP). Both sensitivity and efficacy of SNP-induced relaxations were unchanged in the PG:VG group (EC
50
: 8.8±0.8nM; % relaxation: -99.0±0.3%) vs air group (EC
50
: 11.1±1.0nM; % relaxation: -99.1±0.3%) indicating a loss of ACh responsiveness was independent of VSM. To test whether eNOS was altered by PG:VG, PE response was done in presence of eNOS inhibitor (LNAME). The ‘PE contraction ratio’ (i.e., Tension
PE+LNAME
/ Tension
PE alone
) was significantly decreased in PG:VG group (1.28±0.03) vs air group (1.39±0.20; P<0.05) re-enforcing that PG:VG depressed eNOS function and/or NO bioavailability.

Conclusions:
Acute exposure to E-cig solvent aerosol alone led to endothelial dysfunction and immune cell changes suggesting that E-cig use may increase CVD risk independently of nicotine and flavor constituents. Perhaps thermal degradation of PG and VG into aldehydes may contribute to endothelial dysfunction.
Abstract 17108: Natural History of Cardiomyopathy and Cardiac Stress Response in Young Dogs With Golden Retriever Muscular Dystrophy
Authors: Guo Lee-Jae , Bettis Amanda K , Nghiem Peter P , Soslow Jonathan H , SPURNEY Christopher F , Kornegay Joe N
Published: November 2020

Introduction:
Duchenne muscular dystrophy (DMD) and the genetically homologous model, golden retriever muscular dystrophy (GRMD), are x-linked conditions that cause progressive muscle wasting and cardiomyopathy. We previously defined a late onset DMD-like dilated cardiomyopathy in adult GRMD dogs and aimed to extend that work to young dogs used for preclinical studies. The goal of this study was to characterize the early natural history and cardiac stress response of GRMD cardiomyopathy.

Methods:
A prospective imaging study was completed in 10 GRMD dogs and 8 age-matched normal littermates at 3, 6, and 12 months of age. Electrocardiography (ECG), echocardiography with speckle tracking, and cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and myocardial T1 mapping were assessed. In an effort to identify early subclinical evidence of cardiomyopathy, we conducted a dobutamine stress test in an additional subset of dogs (17 GRMD vs. 6 normal). Fractional shortening (FS) was assessed using echocardiography during dobutamine infusion (5-25 μg/kg/min) at 2 months of age, with follow up studies (4 GRMD vs. 6 normal) at 4.5 and 6 months.

Results:
Heart rate and ECG Q/R ratios (lead II, III, and aVF) were greater in GRMD dogs at 12 months (p<0.04 for all), and PR interval was shortened at 6 months (p=0.02). No systolic functional differences were seen between GRMD and normal dogs using echocardiography. No differences in circumferential strain were seen. CMR left ventricular end-diastolic volume, end-systolic volume, and myocardial mass were smaller in GRMD dogs from 6 months onward (p=0.014, 0.008, and 0.0013). LGE and extracellular volume calculated from T1 mapping did not differ on CMR. A diminished inotropic response, shown by a lower increase of FS (ΔFS), was seen in GRMD dogs during the dobutamine stress test (beginning at a dose of 5 μg/kg/min, 13.9±4.8% vs. 21.8±3.0%, p=0.003) at 2 months of age but not at 4.5 and 6 months.

Conclusions:
We demonstrated ECG changes and heart size differences in GRMD dogs as early as 6-12 months of age. While cardiac function was preserved, the inotropic response to dobutamine stress was blunted in 2-month-old GRMD dogs, potentially providing an early subclinical marker for DMD therapeutic research.