bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16465: Mode of Death and Outcomes of Implantable Cardioverter Defibrillators in Transthyretin Cardiac Amyloidosis
Authors: Dale Zack , Rashdan Lana , Chandrashekar Pranav , Heitner Stephen B , Nazer Babak , Masri Ahmad
Published: May 2021

Introduction:
Patients with transthyretin cardiac amyloidosis (ATTR-CM) may have higher risk of sudden cardiac death yet the role of implantable cardioverter defibrillators (ICD) remains poorly defined. We report our experience with ICDs in a cohort with ATTR-CM.

Methods:
A single center observational cohort study of patients who had been seen at our Amyloidosis Center with either wild-type or hereditary ATTR-CM diagnosed between 2005-2019. ICD implant was at discretion of treating cardiologists. Device data was obtained from record review.

Results:
Ninety-seven patients with ATTR-CM (mean age 71.4±11 years, 89.7% male) had mean follow-up 2.2±1.9 years. Twenty-one patients (21.6%) got ICD - 19 for primary prevention and 2 for secondary prevention - with cumulative 137 interrogations over mean 2.0±2.7 years of device follow-up. In patients with primary prevention ICD, 1 patient got 2 inappropriate shocks - both for 1 episode of atrial flutter in the VT therapy zone; 1 patient got appropriate ATP on 3 occasions. In those with secondary prevention ICD, 1 patient got 15 appropriate shocks for 3 discrete episodes of VT storm; the other got ATP for 1 episode of monomorphic VT. In patients without ICD, 101 ambulatory monitors were reviewed (cumulative 12,313 hours) without sustained ventricular arrhythmia. In this group, 13/76 met at least a class IIB criterion for ICD per current guidelines. EF was higher in those without ICD versus with primary prevention ICD (45.0±13.9 vs 33.4±15.1 %, p=<0.01). Death was seen with similar frequency in those with primary prevention ICD and those without ICD (p=0.60) and mode of death did not vary between them (Table 1).

Conclusions:
Patients with ATTR-CM and primary prevention ICD have low rates of appropriate device therapy without differing in mode of death compared to those with no ICD. Use of ICD for secondary prevention was uncommon but all patients got appropriate device therapy. Further study on ICDs in ATTR-CM is needed to inform best care.
Abstract 16473: Loss of the Apelin-Apelin Receptor Signaling Axis Worsens Hemodynamic Alterations and Right Ventricular (rv) Adaptation and Abrogates 17ß-Estradiol (E2)-Mediated Protection in Experimental Pulmonary Arterial Hypertension (PAH)
Authors: Frump Andrea L , Cook Todd , Fisher Amanda , Nadeau Valerie , Provencher Steeve , Bonnet Sebastien , Lahm Tim
Published: May 2021

Introduction:
Women are more likely to develop PAH but exhibit more favorable hemodynamics and better survival than men. These improved outcomes have been linked to protective effects of E2. We recently linked RV-protective effects of E2 to regulation of apelin signaling. However, the role of apelin and its receptor APJ in RV failure is unknown.

Hypothesis:
RV cardiomyocytes (RVCM)-derived apelin exerts beneficial effects on RV endothelial cells (RVECs). Apelin-APJ signaling is necessary for E2’s RV-protective effects.

Methods:
Apelin and APJ abundance were quantified (Western blot) and immunolocalized in RVs from PAH patients.
In vivo
, RV failure was induced in male Sprague-Dawley rats by pulmonary artery banding (PAB). A subset of PAB rats were treated with E2 ± APJ inhibitor ML221. Hemodynamics, RV function and molecular changes were assessed. To study the role of RVCM apelin, conditioned media was collected from RVCMs after apelin knockdown and then added to RVECs. In addition, conditioned media from untreated RVCMs was added to RVECs pretreated with ML221. Lastly, RVECs were treated with E2 ± siApelin or ML221. p<0.05 was considered statistically significant.

Results:
In PAH RVs, apelin and APJ localized to RVCMs and RVECs and were decreased vs controls (p<0.05). In PAB+E2+ML221 rats, inhibition of apelin signaling resulted in more RV hypertrophy and decreased RV function (p<0.05 vs sham or PAB+E2). Conditioned media from RVCMs+siApelin reduced RVEC eNOS phosphorylation, transwell migration and ring formation (p<0.05 vs scrambled control conditioned media). Concomitantly, treatment of RVECs with ML221 blocked transwell migration and ring formation induced by RVCM conditioned media (p<0.05 vs RVEC+veh control). Lastly, treatment of RVECs with siApelin or ML221 abrogated stimulatory effects of E2 on angiogenic function (p<0.05).

Conclusions:
Apelin and APJ are decreased in PAH-RVs and loss of apelin-APJ signaling results in more severe RV failure and abrogates E2-mediated RV protection. Apelin is secreted by RVCMs and exerts a beneficial paracrine effect on RVECs, where it is required for E2 to stimulate angiogenesis. Apelin-APJ signaling may represent a novel and therapeutically targetable, cell- and sex-specific signaling axis in the RV.
Abstract 16486: Consistent Cost-effectiveness of Icosapent Ethyl Across Patient Profiles From REDUCE-IT
Authors: Zhang Zugui , Bhatt Deepak L , Dolman Sarahfaye , Boden William E , Steg Philippe G , Miller Michael , Brinton Eliot A , King Jordan B , Bress Adam P , Jacobson Terry A , Tardif Jean-Claude , Ballantyne Christie M , Kolm Paul , Weintraub William S
Published: May 2021

Background:
The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) showed that patients with elevated baseline triglycerides (TG) and well-controlled LDL-C levels on statins had a 30% lower risk of total cardiovascular events with 4g of icosapent ethyl (IPE) daily compared to standard care (SC) during a median 4.9 year follow-up. The purpose of this study was to conduct subgroup analyses of lifetime cost-effectiveness (CE) of IPE compared to SC alone.

Methods:
Applying treatment effects from REDUCE-IT, health care costs from the National Inpatient Sample (NIS), and net costs for IPE of $4.16 a day, we conducted a combination CE analysis utilizing patient level in-trial cost and clinical outcomes with long-term costs, events, and life expectancy derived from Markov simulation models. The model projected lifetime health care costs, cardiovascular events, survival, and quality-adjusted life-years (QALYs) for IPE vs. SC from a payer perspective among overall trial-eligible patients and in key subgroups.

Results:
The lifetime mean costs for IPE and SC were $196,080 and $197,064, and the lifetime QALYs for IPE and SC were 10.61 and 10.35, respectively (Table 1). IPE was a dominant strategy over the lifetime in 69.7% of simulations with the probability of CE at the nominal $50,000, $100,000, and $150,000 thresholds being replicated in 87.9%, 98.6%, and 99.9% of simulations, respectively. In the subgroups of age <65 years, male sex, subjects with or without diabetes, secondary prevention cohort, TG levels ≥200 or ≥150 mg/dL, and baseline LDL≥70 mg/dL, IPE was a dominant strategy over the lifetime. In women or the primary prevention cohort, IPE was cost-effective with an ICER of $16,660 or $21,890 per QALY gained, respectively.

Conclusions:
In all subgroups, IPE at a cost of $4.16/day was shown to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY and was a dominant treatment strategy in most subgroups.
Abstract 16488: Rural-urban Disparities in Hospital Care and Mortality Among Older Adults With Acute Myocardial Infarction, Heart Failure, and Ischemic Stroke in the United States
Authors: Loccoh Emefah C , Joynt Maddox Karen E , Wang Yun , Kazi Dhruv , Yeh Robert W , Wadhera Rishi
Published: May 2021

Introduction:
Over the last decade, disparities in cardiovascular mortality have widened between rural and urban areas of the US. Our objective was to determine whether there were differences in treatment patterns and outcomes for acute cardiovascular conditions at rural and urban hospitals.

Methods:
We used 100% Medicare Claims to identify beneficiaries age 65 years hospitalized 1/1/2016-12/31/2017 for acute myocardial infarction (AMI), heart failure (HF), and ischemic stroke. We fit a mixed effects model with a logit link function and hospital random intercepts to evaluate condition-specific procedure rates (PCI/CABG, cerebral arteriography, systemic thrombolysis) and 30-day and 1-year mortality rates for beneficiaries admitted to rural vs. urban hospitals, adjusted for age, sex, dual enrollment, and clinical comorbidities.

Results:
Our study included 398,673 beneficiaries hospitalized for AMI (mean age 77.3 years), 690,218 for heart failure (80.3 years), and 378,170 for stroke (79.4 years). The proportion of AMI, HF, and stroke hospitalizations that occurred at rural hospitals was 10.7%, 14.2%, and 10.6%. Procedures were performed less frequently for beneficiaries admitted to rural compared with urban hospitals (PCI/CABG within 30 days of AMI: adjusted odds ratio [aOR] 0.50, 95% CI 0.47-0.54; cerebral arteriography [aOR 0.15, 0.11-0.22]; and systemic thrombolysis [aOR 0.47, 0.43-0.52] for stroke). Thirty-day mortality was higher at rural vs. urban hospitals for AMI (aOR 1.26, 1.21-1.31), HF (aOR 1.14, 1.11-1.17) and stroke (aOR 1.11, 1.07-1.16), as was 1-year mortality (AMI: aOR 1.31, 1.26-1.35; HF: aOR 1.10, 1.08-1.12; Stroke: aOR 1.14, 1.10-1.17).

Conclusion:
Older adults admitted to rural hospitals for acute cardiovascular conditions receive lower intensity care and experience higher mortality rates than those admitted to urban hospitals. Policy initiatives that improve cardiovascular care at rural hospitals are urgently needed.
Abstract 16501: Intravenous Administration of Neonatal Mesenchymal Stem Cells Mediates Functional Recovery in a Renal Ischemia-reperfusion Injury Rodent Model
Authors: Shah Aakash M , Abdullah Mohamed , Davidson Lauren , Saha Progyparamita , Gunasekaran Muthukumar , Mishra Rachana , Sharma Sudhish , Kaushal Sunjay
Published: May 2021

Introduction:
The prevalence of acute kidney injury in cardiac surgery patients is up to 30%. However, treatments to facilitate kidney recovery are mainly limited to supportive care. In preclinical studies, stem cell therapy using adult Mesenchymal Stem Cells (aMSCs) has reduced kidney damage through the secretion of paracrine factors. Previously, we have established that our neonatal Mesenchymal Stem Cells (nMSCs) have a more potent anti-inflammatory and pro-angiogenic secretome profile than aMSCs.

Hypothesis:
Intravenous administration of nMSCs and their secretome (total conditioning media) will diminish kidney injury in a renal ischemia-reperfusion injury rodent model.

Methods:
Six to seven-week-old Brown-Norway rodents underwent bilateral renal clamping to induce 90-minute ischemia. After removal of the clamps and renal reperfusion, the rodents were injected with 100 uL of PlasmaLyte A (control; n=7), an nMSC suspension (10 million cells/kg; n=6), or a total conditioning media (TCM) suspension (10 mg/kg; n=6) via their lateral tail vein.

Results:
One day after nMSC and TCM treatment, both blood urea nitrogen (116.08 ± 12.02 vs 149.41 ± 9.26 mg/dL; *p=0.0434 and 111.34 ± 9.54 vs 149.41 ± 9.26 mg/dL; *p=0.0174, respectively) and blood creatinine (0.75 ± 0.074 vs 1.25 ± 0.18 mg/dL; **p=0.0028 and 0.76 ± 0.06 vs 1.25 ± 0.18 mg/dL; **p=0.0030, respectively) levels were significantly reduced compared to after PlasmaLyte A injection. Associated decreases in pro-apoptotic signaling molecules (CASP8, BAK, and BAD) and increases in anti-apoptotic signaling molecules (pAKT, SOD2, and BCL2) are being investigated.

Conclusions:
nMSC and TCM treatment via intravenous injection showed indications of a reduction in kidney injury. This therapy should be further investigated for use in select cardiac surgery patients.
Abstract 16529: Frailty in Fontan Patients - A Sign of Premature Aging?
Authors: Ouimet Grennan Erika , Guerrero Carlos , Therrien Judith , Liu Aihua , Guo Liming , Afilalo Jonathan , Marelli Ariane J
Published: May 2021

Introduction:
Patients submitted to a Fontan operation sustain a lifelong state of reduced cardiac output and increased venous pressure potentially inducing premature aging. We hypothesize that Fontan patients, despite their young age, resemble more elderly patients compared to age-matched controls.

Methods:
At a tertiary care center, we evaluated 17 Fontan patients who had a recent abdominal CT scan for Fontan associated liver disease follow-up. Psoas muscle area (PMA), a recognized marker of frailty, was measured on the axial plane at the level of L4. The distributions of PMA scores were compared between Fontan and 1) patients undergoing a transcatheter aortic valve replacement (TAVR); and 2) an age-matched healthy cohort, separately with Kruskal-Wallis test.

Results:
The Fontan group comprised six males and 11 females aged 19-40. The proportions of systemic left ventricle and heterotaxy syndrome were 82% and 18% respectively in females and 33% and 33% respectively in males. The TAVR cohort included 241 males and 184 females aged 70-99. The healthy cohort enrolled 59 males and 66 females age-matched to the Fontan group. Among the Fontan patients, median and interquartile range of PMA were 18.1, 14.85-21.12 cm2 in females and 23.41, 22.25-30.21 cm2 in males. The comparison between the groups for males (Panel A) and females (Panel B) are illustrated in the Figure.

Conclusions:
Males Fontan appear to have reduced muscle mass that resembles more patients who are candidates for TAVR than aged-matched controls, an observation that, interestingly, was not seen in females in this small well-characterized cohort. To our knowledge, this is the first study to document a direct comparison of Fontan patients to other subgroups illustrating a mismatch between chronological and biological age in Fontan. Further studies are needed to elucidate the possible protective effect of female sex.
Abstract 16538: Circulating Ketone Levels are Associated With Myocardial Infarct Size and Left Ventricular Function in Patients Presenting With St-Elevation Myocardial Infarction
Authors: de Koning Marie Sophie L , Westenbrink B. D , Assa Solmaz , van Veldhuisen Dirk J , Dullaart Robin P , Lipsic Erik , Van Der Harst Pim
Published: May 2021

Background:
Circulating ketone bodies (KB) are increased in patients with heart failure, corresponding with increased utilization of KB as a cardiac fuel. Whether circulating KB are increased in patients presenting with ST-elevation myocardial infarction (STEMI) and whether this is associated with infarct size is unknown.

Methods:
KB were measured in 379 non-diabetic participants of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction (GIPS) III trial (Clinicaltrial.gov Identifier: NCT01217307). Non-fasting plasma concentrations of the KB beta-hydroxybutyrate, acetoacetate, acetone were measured at presentation, 24 hours and 4 months after STEMI presentation using nuclear magnetic resonance spectroscopy. Associations of circulating KB with myocardial infarct size and left ventricular ejection fraction (both detected with MRI at 4 months after STEMI) were determined using multivariable linear regression analyses.

Results:
Circulating KB were higher at baseline (total KB 520 [315-997](median [IQR], μmol/L), compared to 206 [174-246] at 24 hours and 166 [143-201] at 4 months (
P
<0.001 for all)). KB at 24 hours were positively associated with enzymatic infarct size, HbA1C and beta-blocker use. KB at 24 hours were independently associated with MRI outcomes at 4 months. Higher KB was associated with larger myocardial infarct size (total KB: standardized β=0.17, 95%-confidence interval (CI) (0.04-0.31),
P
=0.012) and lower ejection fraction (standardized β=-0.15, 95%-CI (-0.29- -0.009),
P
=0.037).

Conclusion:
Circulating KB are increased in patients with STEMI and are independently associated with myocardial infarct size and left ventricular function after 4 months of follow-up. The increase in circulating KB may reflect maladaptive changes of myocardial metabolism during the acute phase.
Abstract 16542: Hypotension and Pericardial Effusion Associated With High Frequency Jet Ventilation
Authors: Tung Patricia , Waks Jonathan W , Buxton Alfred E
Published: May 2021

Introduction:
High frequency jet ventilation (HFJV) is used to increase catheter stability and improve outcomes during pulmonary vein isolation (PVI) [1,2,4]. In studies, hemodynamic intolerance of HFJV was rare. [1,3].

Hypothesis:
HFJV during PVI is well tolerated and vasopressor-resistant hypotension requiring return to conventional ventilation is rare.

Methods:
Retrospective observational analysis of hemodynamic, blood gas, and echocardiographic data of PVIs performed with HFJV by 2 operators (PT, JW) at our institution between February 2019 and June 2020.

Results:
Among 193 PVIs, 8 cases (4%) of rapid onset hypotension associated with HFJV were found (Table). In 7 of 8 cases, persistent hypotension and abnormal gas exchange required conversion to conventional ventilation and a new, small pericardial effusion without tamponade was noted just after HFJV initiation. In these cases, initiation of HFJV was associated with a decrease in systolic function. Both the hemodynamic changes and effusion resolved completely within minutes of stopping HFJV. Four of 8 patients were rechallenged with HFJV, and had recurrent hypotension and effusion which resolved immediately after return to conventional ventilation.

Conclusions:
HFJV-associated rapid onset hypotension, often accompanied by transient pericardial effusion, is more common than previously reported, and resolves with cessation of HFJV. The mechanism of these changes may occur via CO2 levels and warrants further study.
Abstract 16548: Low-dose Amiodarone for Control of Atrial Fibrillation (AF) Remains Effective in Patients With Ejection Fraction Less Than 50%
Authors: McGrew Frank A , Charlton Sandy , Dragutsky Brian
Published: May 2021

Introduction:
Our previous work has shown low-dose Amiodarone (often less than 600 mg per week) is effective for control of AF in a forced down-titration schema. Many studies have shown restoration of sinus rhythm in patients with CHF shows promise for reduced mortality and morbidity. This analysis compares results of this protocol in patients with ejection fraction above and below 50%.

Methods:
Consecutive patients with atrial fibrillation deemed suitable for Amiodarone therapy were prospectively followed with a forced down-titration protocol. Controlled atrial fibrillation was defined as an AF burden of less than 1% on device diagnostics (30% of patients) or no symptoms and sinus rhythm on clinical visit EKGs. Demographic and clinical data were analyzed for patients with ejection fraction above and below 50%.

Results:
Patients with EF less than 50% had greater success (35/38) or 92% than patients with ejection fraction greater than 50% (39/51) or 76%. However, patients with ejection fraction under 50% required larger doses. See graph for detailed doses. Overall success was good in both groups with no sustained side effects.

Conclusions:
Amiodarone in low doses is effective in control of atrial fibrillation in patients across the spectrum of ejection fractions. Lower ejection fractions may require a somewhat higher dose (less than 1000 mg per week) but at a higher success rate.Larger studies could potentially show the impact of this protocol on mortality.
Abstract 16567: Long-Term Vascular Function in CTO Recanalization. A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel
Authors: Rodriguez Arias Juan Jose , Gomez-Lara Josep , Caballero-Borrego Juan , Ortega-Paz Luis , Teruel Luis , Gil-Jimenez Teresa , Oyarzabal Loreto , Romaguera Rafael , Moreno Terribas Gerardo , Gomez Joan Antoni , Sabate Manel , Brugaletta Salvatore
Published: May 2021

Background:
Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT) with ticagrelor vs. clopidogrel.

Methods:
The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up.

Results:
Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively). A higher CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p=0.027), was maintained at follow-up (AUC 34815.22±24206.06 vs. AUC 22712.47±13768.95; p=0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p=0.933), clopidogrel loading dose-related CBF increased at follow-up (p=0.039).

Conclusion:
The TIGER trial showed that DAPT with ticagrelor may maintain a higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with slight increase at follow-up. The clinical value of such sustained higher coronary flow should be evaluated in a larger group of patients.
Abstract 16569: Psychosocial Risk Factors for Depression in Women With Myocardial Infarction: Mindfulness and Rumination
Authors: Sperber Sarah H , Duberstein Zoe T , Kalinowski Jolaade , Reynolds Harmony R , Berger Jeffrey S , Spruill Tanya M
Published: May 2021

Introduction:
Depression is associated with adverse health outcomes in women with myocardial infarction (MI). Little is known about modifiable psychosocial risk factors for depression in this population. We analyzed baseline data from an ongoing multicenter clinical trial to test the hypothesis that depressive symptom severity is associated with low mindfulness and high rumination, two psychosocial factors targeted by the mindfulness-based cognitive therapy (MBCT) program being tested.

Methods:
Women with MI reporting elevated stress levels ≥2 months post-MI are eligible for the trial. Participants complete baseline measures including demographics, medical history and validated measures of depressive symptoms (Patient Health Questionnaire [PHQ-9]), mindfulness (Five Facet Mindfulness Questionnaire [FFMQ]), rumination (Rumination-Reflection Questionnaire [RRQ]) and disease-specific quality of life (Seattle Angina Questionnaire [SAQ-7]). Pearson correlation coefficients and multivariable linear regression were used to identify correlates of baseline depressive symptoms.

Results:
The 127 participants had a mean age of 60.0 years (SD=12.8); 33.1% were racial or ethnic minorities and 16.5% were participating in cardiac rehabilitation. The mean PHQ-9 score was 7.5 (SD=4.7), 31.5% of participants had elevated depressive symptoms (PHQ-9≥10) and 23.6% were taking antidepressant medication. In univariate analyses, higher depressive symptoms were associated with higher rumination (r=.412, p<.001) and lower mindfulness (r=-.370, p<.001). In multivariable analysis, higher depressive symptoms were associated with higher rumination (B=.253, p=.005), financial strain (B=.180, p=.02), lower SAQ score (B=-.269, p=.001) and use of antidepressant medication (B=.283, p<.001). Mindfulness, age, race/ethnicity, marital status and cardiac rehab were not associated.

Conclusions:
About one-third of women reported clinically significant depressive symptoms after acute recovery from MI. Higher depressive symptoms were independently associated with higher levels of rumination. Future analyses will test whether hypothesized effects of MBCT on depression in post-MI women are mediated by reductions in negative thought patterns.
Abstract 16574: Short Term Outcomes With Mitraclip in Women Compared With Men: Evidence From a Meta-analysis
Authors: Khallid Yaser , Dasu Neethi , Dasu Kirti
Published: May 2021

Introduction:
MitraClip is now approved for severe functional mitral regurgitation in high-risk patients with contraindications to surgical mitral valve repair. Previous studies have shown conflicting results with respect to sex differences in outcomes with the MitraClip. This study sought to examine short-term outcomes with transcatheter mitraclip in women versus men.

Hypothesis:
Female patients will have higher all-cause mortality, major cardiovascular events, and complications than men following MitraClip.

Methods:
Electronic search was performed until April 2020 for studies reporting outcomes with MitraClip in women versus men. Random effects DerSimonian-Laird odds ratios were calculated. Outcomes included all-cause mortality and major cardiovascular events at short-term follow-up (in hospital or 30 days) as well as complications.

Results:
Six studies (4 MitraClip registries; 2344 patients; 925 women) were analyzed. Women were older but exhibited fewer comorbidities. At 30 days, men had more strokes (p < 0.0347) and major vascular complications (p < 0.042), without a difference in all-cause and cardiovascular mortality (OR 1.31, 0.67-2.57, p <0.43) compared with men. There was no difference in pericardial effusion/cardiac tamponade (p <0.311) or acute renal failure (p <0.805). The female survival advantage remained consistent across multiple secondary analyses. The risk of stroke, moderate/severe aortic insufficiency, and all-cause mortality seemed to vary based on the type of valve used; however, without significant subgroup interactions.

Conclusions:
Despite conflicting data, women experience better short-term outcomes with the MitraClip repair.
Abstract 16592: Excessive MCU-Mediated Mitochondrial Calcium Uptake During Chronic Stress Impairs Cardiac Contractility
Authors: Garbincius Joanne F , Luongo Timothy S , Lambert Jonathan P , Mangold Adam S , Murray Emma K , Hildebrand Alycia N , Jadiya Pooja , Elrod John W
Published: May 2021

Calcium (Ca
2+
) uptake into the mitochondrial matrix occurs via the mitochondrial Ca
2+
uniporter channel (mtCU) and tunes mitochondrial metabolism to meet acute changes in cellular ATP demand. However, the role of mtCU-dependent mitochondrial Ca
2+
(
m
Ca
2+
) uptake in regulating homeostatic heart function and adaptation to chronic increases in workload remain controversial. We subjected mice with tamoxifen-inducible, cardiomyocyte-specific gain (flox-stop-MCU x αMHC-MCM, MCU-Tg) or loss (

Mcu
fl/fl

x αMHC-MCM
, Mcu-
cKO) of MCU function to 2wk isoproterenol (iso) infusion to test the hypothesis that
m
Ca
2+
uptake through MCU contributes to functional adaptation to sustained catecholamine signaling. Neither gain nor loss of MCU function altered baseline cardiac structure or function. Fractional shortening was increased after 2d of iso infusion in MCM control mice, but loss of MCU blocked this effect. In contrast, fractional shortening declined significantly after 7-14d of iso in MCU-Tg mice. MCU-Tg mice also exhibited increased LV dilation, heart mass, and lung edema compared to controls after 14d of iso. Acute treatment of MCU-Tg cardiomyocytes
in vitro
with the Ca
2+
ionophore ionomycin revealed increased ROS production and a trend towards increased sensitivity to Ca
2+
-induced cell death. In agreement, Evans blue dye exclusion assays revealed increased cardiomyocyte necrosis in MCU-Tg hearts following iso. Therefore, we deleted the mPTP regulator cyclophilin D (CypD) in MCU-Tg mice to test whether cardiomyocyte dropout due to
m
Ca
2+
overload-induced mPTP contributed to iso-induced contractile dysfunction. Unexpectedly, CypD deletion failed to attenuate contractile dysfunction and hypertrophic remodeling, and increased rather than attenuated iso-induced cardiomyocyte death in MCU-Tg mice. We conclude that while MCU-dependent
m
Ca
2+
uptake is required for the heart’s initial contractile response to catecholaminergic stress, under prolonged stimulation augmented
m
Ca
2+
uptake becomes deleterious and predisposes to cardiomyocyte death and heart failure. Our findings support the notion that the detrimental effects of sustained MCU-dependent
m
Ca
2+
uptake are mediated by mechanisms distinct from mitochondrial permeability transition.
Abstract 16597: Outcomes of a Randomized Controlled Trial of Integrated Cardiac Rehabilitation Among Heart Failure Patients in Kenya
Authors: Ngeno G.Titus K , Barasa Felix A , Kwobah Edith , Kamano Jemima , Vedanthan Rajesh , Knettel Brandon , Navuluri Neelima , Egger Joseph R , Thielman Nathan , Kussin Peter , Kraus William E , Bloomfield Gerald S
Published: May 2021

Background:
Cardiac rehabilitation (CR) is an evidence based, cost effective treatment for heart failure (HF). Globally, access to CR is limited, especially in low- and middle-income countries. An integrated model of institutional and home-based CR has been proposed as a solution to access barriers. However, the efficacy of integrated CR in this region is unknown. We performed a randomized controlled trial of integrated CR compared to usual care (no CR) among patients with stable HF in western Kenya.

Methods:
Patients with class II or III NYHA symptoms were enrolled from the Moi Teaching and Referral Hospital. Participants with arrhythmias, congenital heart disease, or stenotic valvular heart disease were excluded. Integrated CR comprised of counseling and supervised aerobic exercises 3 times a week for 1 month, followed by 2 months of monitored home-based exercises prescribed weekly via phone. Participants in both arms received health lifestyle education and wore triaxial hip pedometers. The primary outcome, change in 6-minute walk time distance (6MWTD), as well as weekly step counts were compared using the Student’s t-test.

Results:
Eighty-two participants were randomized (Figure). 6MWTD improved significantly more among the 41 patients receiving CR (45 ± 67m from baseline), compared to the usual care arm (18 ± 49m in, p<0.05), (Table). There was no significant difference in change by age, gender, BMI, ejection fraction or reported HF cause.

Conclusions:
Integrated CR improves 6MWTD among patients with HF. The findings are limited to a single center. Future studies on long-term outcomes and mechanistic processes responsible for improvement are needed.
Abstract 16601: Impact of Insurance Status on Emergent Versus Non-Emergent Hospital Encounters Among Adults With Congenital Heart Disease
Authors: Agarwal Anushree , GURVITZ Michelle Z , Myers Janet , Jain Sarthak , Khan Abigail , nah gregory , Harris Ian S , Mahadevan Vaikom S , Kouretas Peter C , Marcus Gregory M
Published: May 2021

Background:
Arguments against universal health insurance are ongoing, but insurance coverage may be beneficial in high-risk populations such as adults with congenital heart disease (ACHD). While the number of hospital visits have exponentially increased for ACHD over the last few decades, the impact of insurance on the type of hospital encounters remains unknown.

Hypothesis:
Uninsured ACHD patients are more likely to have emergent hospital encounters than those insured.

Methods:
Using California Office of Statewide Health Planning and Development Database from 01/2005 to 10/2015, we identified all hospital encounters that were emergent (which might or might not have resulted in an admission) or nonemergent among ACHD ≥18 years old. We determined the trends over time and odds of insurance status on emergent vs. nonemergent encounters.

Results:
Among 69,876,425 encounters, 72,142 were in patients with CHD diagnoses (mean age 49±12 years, 43% males, 52% Caucasian, 4% uninsured). 78% had severe CHD and 75% had a comorbidity. From 2005 to 2015, while all ACHD encounters increased by 108% (p for trend <0.0001), there was significantly higher increase in emergent than nonemergent encounters (331% vs. 87%; p<0.0001). The ratio of emergent:nonemergent encounters was significantly higher for uninsured than insured patients (3.18 vs. 1.02; p<0.0001). Non-cardiac diagnoses were more common among emergent than non-emergent encounters (68% vs. 36%; p<0.0001). Both before and after multivariable adjustment, uninsured status was associated with a significantly higher odds of emergent encounters for all ACHD (Figure), irrespective of CHD type, exhibiting the largest magnitude of effect compared to any other predictor.

Conclusions:
Efforts to enhance the ability to obtain and maintain insurance throughout the lifetime of ACHD patients might result in meaningful reductions in emergency encounters and a more efficient use of resources.
Abstract 16628: Cognitive Dysfunction, Instrumental Activities of Daily Living, and Health-related Quality of Life in Heart Failure
Authors: Jung Miyeon , Giordani Bruno , Gao Sujuan , Burney Heather , Titler Marita G , Smith Dean G , Dorsey Susan , Haedtke Christine , Wierenga Kelly L , David Clark G , Gradus-Pizlo Irmina , Pressler Susan J
Published: May 2021

Introduction:
Cognitive dysfunction is common in heart failure (HF), but relationships are unclear among cognitive dysfunction, performance-based instrumental activities of daily living (IADL), and health-related quality life (HRQL).

Objectives:
Guided by HRQL and IADL theories, hypotheses were: 1) worse cognitive function in global cognition, memory, executive function is associated with worse performance in IADL; 2) worse performance in IADL is associated with worse HRQL; and 3) IADL mediates the relationship between cognitive dysfunction and HRQL.

Methods:
In a cross-sectional analysis, baseline data were used from a randomized controlled trial of cognitive training in HF (N=256, mean age 66; 54% women; EF 49%; NYHA Class I=9%, II=36%, III=55%). Measures were: global cognition-Montreal Cognitive Assessment; memory-Hopkins Verbal Learning Test; executive function-Category fluency; IADL-Everyday Problem Test; and HRQL-Living with Heart Failure Questionnaire. Higher scores of cognitive and IADL measures indicate better performance. Higher scores of HRQL indicate worse HRQL. Covariates were age, gender, education, NYHA, and depressive symptoms. Multiple linear regressions were used to test hypotheses.

Results:
Hypothesis 1 was supported. Worse cognitive function in global cognition, memory, executive function was associated with worse IADL (β=0.38~0.45, p<.001, R
2
=0.19~0.22). Age and education were significant covariates. Hypothesis 2 was supported. Worse IADL was associated with worse HRQL (β =0.79, p <.001, R
2
=0.55). Gender, NYHA Class, and depressive symptoms were significant covariates. Hypothesis 3 was not tested because cognitive function was not significantly related to HRQL.

Conclusions:
Cognitive dysfunction was associated with worse performance in IADL. Worse performance in IADL was associated with worse HRQL. Interventions to improve HRQL may need to target improving performances in both cognitive function and IADL.
Abstract 16632: Clinical Characteristics and In-Hospital Outcomes of Covid-19 Patients With Ecg St Segment Elevation: A System Wide Analysis
Authors: SINGH Avneet , Meraj Perwaiz , Reddy Arvind , Mahmood Eitezaz , Ali Ibrahim , Avadhani Sriya , Mountantonakis Stavros , Gandotra Puneet , Ong Lawrence , Gruberg Luis , jauhar rajiv
Published: May 2021

Myocardial injury is seen in approximately 20% of COVID-19 patients and ST elevation myocardial infarction may be the presenting clinical manifestation. Recent data suggest that the ST-segment elevation (STE) may be due to myopericarditis. We assessed the clinical characteristics, electrocardiographic patterns, incidence, management and outcomes of COVID-19 pts with STE.

Methods:
We analyzed 23,406 ECGs (10,018 pts) admitted to 13 New York City area hospitals between March 1 and April 30, 2020.

Results:
After manual adjudication, 51 (0.5%) had focal STE, 22 (0.2%) had diffuse STE and 9,945 did not have STE. Baseline clinical characteristics were similar among the three groups, albeit a higher percentage of pts with low ejection fraction in the diffuse STE group. Cardiac catheterization was performed on 10 pts. Three pts did not have obstructive disease. Pts with focal STE were more likely to require inotropes and die during index hospitalization. Kaplan-Meier estimated overall survival rates were 31%, 33% and 6% in patients without STE, focal and diffuse STE, respectively (p < 0.0001) (Figure). By stepwise logistic regression analysis, focal STE was the strongest predictor of death (OR=7.0; CI 3.8-13.0, p<0 .0001) followed by age > 65 years (OR=3.5; CI 3.1-3.9; p<0.0001) and diffuse STE (OR=2.9; CI 1.1-7.2; p<0.0001). Female gender was associated with a decreased risk (OR 0.72; CI, 0.65-0.79; p<0.0001).

Conclusions:
In this large retrospective analysis of 10,018 COVID-19 pts, we observed that: 1) a very small percentage (0.7%) presented with STE; 2) 70% had focal STE and 30% had diffuse STE; 3) a minority underwent coronary angiography; 4) in-hospital mortality rates were very high for pts with STE, and even more so for those with focal STE (63% vs 46%) and; 5) focal STE was the strongest predictor of in-hospital mortality and female gender was a predictor of survival.
Abstract 16634: Treatment Patterns & Clinical Outcomes Among Asian Americans With Atrial Fibrillation: An Analysis From the NCRD® PINNACLE Registry
Authors: Mahtta Dhruv , Gu Kevin , Kaneria Amar , Sharedalal Parija , Dennis Brittany , Song Yang , Xin Wei , Khalid Mirza , Hess Paul , Cho Sung-Hae , Virani Salim S
Published: May 2021

Introduction:
Although treatment modalities for Atrial Fibrillation (AF) continue to evolve, there is paucity of data on AF management and associated clinical outcomes among Asian Americans (AA). We investigated risk factor profiles, racial disparities in clinical management and associated adverse clinical outcomes among AA compared to Whites.

Hypothesis:
Racial disparities exist between White and AA with regards to AF management and related adverse clinical outcomes.

Methods:
Using the National Cardiovascular Data Registry (NCDR®) Practice Innovation and Clinical Excellence (PINNACLE) registry and linked Centers of Medicare and Medicaid Services data to identify AA and White patients with AF between 1/1/13-6/30/18, we characterized risk factors, management strategies (rate vs. rhythm control), anticoagulation use and rates of adverse events across racial groups. The two race groups were compared using hierarchical multivariable adjusted regression models to account for site and potential confounders.

Results:
Our analysis included 1359827 patients with AF (18793 AA; 1341034 Whites). Compared to Whites, AA were more likely to be treated with rate control strategy (OR:1.20, 95% CI:1.15-1.25) in adjusted analyses. AA had lower odds of use of rhythm control strategy (atrial ablations, cardioversions, or use of antiarrhythmic drugs) (OR:0.83, 95% CI:0.80-0.87). Overall use of oral anticoagulants (OAC) and direct oral anticoagulants were similar across both racial groups. There were no significant race-based differences in likelihood of adverse clinical events including all-cause mortality, strokes, and bleeding. Analyses performed using propensity score matching were consistent with the main results.

Conclusions:
AA with AF have a lower likelihood of being managed with rhythm control strategies. Overall use of OAC and AF related adverse events remain similar between the two racial groups.
Abstract 16635: Enhanced Cardiac Delivery of a Small Soluble Antifibrotic Peptide With Liposomal Encapsulation
Authors: Sonkawade Swati D , Xu Shirley , Pokharel Saraswati , Sharma Umesh C
Published: May 2021

Introduction:
N-acetyl-ser-asp-lys-pro (Ac-SDKP) is an enodogenous anti-fibrotic peptide with a great potential for use as a “
replacement therapy
” in fibrotic myocardial remodeling. However, its therapeutic use is limited by its short half-life (4.5 mins) and a negligible bioavailibity.

Hypothesis:
We hypothesize that liposomal encapsulation of Ac-SDKP (L-Ac-SDKP) enhances its stability, and improves delivery into the myocardial target cells at a higher efficiency than free Ac-SDKP. This will maximize retention time, allowing intermittent dosing and minimizing off-target effects.

Methods:
We synthesized L-Ac-SDKP using zwitterionic lipid formulation for better cell membrane penetration. We used Fluorophore (FITC)-conjugated Ac-SDKP as a tracer, and scrambled peptides and blank liposomes as controls. After confirming an enhanced uptake efficiency of L-Ac-SDKP into the adult cardiac fibroblasts, we performed
in vivo
L-Ac-SDKP uptake and distribution studies in a model of cardiac fibrosis induced by 30Gy of thoracic ionizing radiation exposure.

Results:
Confocal microscopy of the cultured cardiac fibroblasts showed L-Ac-SDKP distribution localized to perinuclear areas corroborating its known effects on cell-cycle and nuclear membrane trafficking compared to the free peptide. Along with flow cytometry analysis L-Ac-SDKP uptake was seen in 98% of cells as opposed to 7% when treated with free Ac-SDKP. In vivo, the mouse model of myocardial fibrosis showed significantly increased L-Ac-SDKP uptake (33±3 fold), compared to normal controls (14±3 fold) after 5 daily injections. Quantification of Ac-SDKP in the cardiac homogenate reached a maximum therapeutic concentration of 1.4 pg/mg after 2 doses in irradiated mice, whereas even higher concentration could be achieved after 5 cumulative doses.

Conclusion:
We conclude that liposomal-conjugation is a highly effective therapeutic approach for targeting cardiac fibrosis using a potent fibroblast inhibitory peptide, Ac-SDKP as a therapeutic agent. Translational studies in large animal models are currently in progress for further testing its therapeutic utility.
Abstract 16637: Echocardiographic Screening With Remote Reading as a Tool for Additional Cardiovascular Risk Stratification in Primary Care - Data From the PROVAR+ Study
Authors: Nascimento Bruno R , Nunes Maria Do Carmo P , SABLE Craig A , Oliveira Kaciane , Franco Juliane , Barbosa Marcia , Reese Alison , Raso Leonardo , Paiva Sarcha M , Diamantino Adriana C , Fraga Clara , Macedo Frederico , Ferreira-Filho Domingos Sávio G , Ribeiro Antonio L , Beaton Andrea Z
Published: May 2021

Introduction:
Morbidity and mortality associated with advanced heart disease (HD) is significant in Brazil. Underserved populations often experience long delays in diagnosis, with long waiting lines for echocardiography (echo). We aimed to evaluate the feasibility of integrating screening echocardiography (echo) with remote interpretation in the Brazilian primary care (PC), and to assess HD prevalence.

Methods:
In 36 months, 25 healthcare workers at 40 PC units were trained on simplified handheld (GE VSCAN) echo protocols. Screening (SC) groups, including patients aged 17-20, 35-40 and 60-65 years, and patients referred (RF) for clinical indications, in waiting lines, answered a clinical questionnaire and underwent focused echo, interpreted in US and Brazil by telemedicine. Significant HD was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A study-derived score including clinical variables (sex, body mass, hypertension, coronary disease, heart failure, heart surgery, valve disease and Chagas disease: low (<13%), intermediate (13% - 69%) and high-risk (≥70%)) was applied to predict HD in echo screening.

Results:
From January 2017 to November 2019, 4425 patients underwent echo; 1338 (30%) in SC group. Mean age was 54±18 years, 63.7% were females; 57.8% had hypertension and 20.1% diabetes. The most frequent symptoms were chest pain (32.3%), dyspnea (32.3%) and palpitations (25.6%). Significant HD was found in 1409 (31.8%) patients, (28.8% in SC vs. 33.2% in RF group, p=0.004). Comparing SC to RF, severe left ventricular dysfunction was observed in 2.6% vs. 3.1%, p=0.45, severe aortic or mitral regurgitation in 1.5% vs. 1.0%, p=0.17. Prevalence was higher in high-risk patients according to the clinical score, compared to intermediate/low risk (45.3% vs. 26.6%, p<0.001). The continuous risk score was strongly associated with HD (odds ratio=25.8, 95% IC 16.5 - 40.4, p<0.001), with area under ROC curve=0.61.

Conclusions:
Integration of screening echo into PC is feasible in Brazil as a strategy to prioritize cardiovascular care in low income areas through task-shifting. In association with clinical variables, this tool may improve early diagnosis and referrals.
Abstract 16639: A Novel Approach to Model Heart Failure With Preserved Ejection Fraction in Rats
Authors: Katsurada Kenichi , Nandi Shyam S , Sharma Neeru M , Patel Kaushik P
Published: May 2021

Introduction:
Diastolic dysfunction and cardiac hypertrophic remodeling are hallmark features of heart failure with preserved ejection fraction (HFpEF) in humans. However, an ideal animal model that mimics all these basic clinical features of HFpEF remains to be developed.

Methods:
Male Sprague-Dawley rats (250-300 g) were subjected to central infusion of either Angiotensin II (Ang II at 20 ng/min, 0.5 μl/h, i.c.v) or isotonic saline (0.5 μl/h, i.c.v) through osmotic mini-pumps for 14 days. Echocardiography was used to measure systolic (ejection fraction) and diastolic functions (E/A and E/E’ ratio) at day 14. Mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), changes in ±dP/dt, and cardiac responses to isoproterenol (ISO) were also measured in anesthetized rats.

Results:
Central infusion of Ang II in rats resulted in increased sympathoexcitation and mean arterial pressure. Concomitantly, there was decreased E/A ratio (AngII: 1.2 ± 0.1 vs. Cont: 1.5 ± 0.1) and increased E/E’ ratio (AngII: 14.3 ± 0.8 vs. Cont: 12.9 ± 0.6), indicating diastolic dysfunction. Ejection fractions were comparable between the groups (AngII: 67 ± 2% vs. Cont: 69 ± 5%). Ang II infused rats demonstrated increased heart to body weight ratio (AngII: 4.5 ± 0.5 vs. Cont: 2.9 ± 0.1), cachexia (AngII: 235 ± 18 g vs. Cont: 331 ± 11 g), hypertrophy (AngII: 46 ± 5 μm/unit area vs. Cont: 36 ± 7 μm/unit area), and fibrosis (AngII: 5.2 ± 0.5 intensity/unit area vs. Cont: 2.6 ± 0.4 intensity/unit area). At the same time cardiac contractile responsiveness to ISO (0.5 μg/kg) was significantly lower for negative dP/dt in Ang II rats (AngII: -6998 mmHg/s vs. Cont: -11675 mmHg/s), which is indicative of abnormal diastole or relaxation. However, positive dP/dt response to ISO was similar in the two groups, indicating preserved systolic function in the Ang II group.

Conclusions:
Central Ang II infusion in rats shows sympathoexcitation, diastolic dysfunction, and pathological cardiac hypertrophy and fibrosis mimicking abnormalities seen in patients with HFpEF. This model of cardiac dysfunction in rats may represent a suitable platform to investigate the underlying mechanisms of HFpEF.