bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14784: Sleep Moderates the Association Between Arterial Stiffness and Blood Pressure Variability
Authors: Liu Xiaoyue , Yan Guofen , Bullock Linda , Barksdale Debra , Logan Jeongok G
Published: May 2021

Introduction:
Both arterial stiffness and short-term blood pressure variability (BPV) are important subclinical biomarkers of cardiovascular disease (CVD). Evidence is accumulating that poor sleep is associated with subclinical CVD. The purpose of our study was to investigate how sleep was related to arterial stiffness and BPV. We also explored if sleep changed the association between arterial stiffness and BPV.

Methods:
In this cross-sectional study, objective sleep characteristics were assessed by a wrist actigraphy over two days. Arterial stiffness was measured by carotid femoral pulse wave velocity (cfPWV). BPV was evaluated using an ambulatory blood pressure monitor over 24 hours and estimated by average real variability.

Results:
The sample included 87 healthy adults aged between 35 and 64 years. Sleep efficiency was an independent predictor of cfPWV and systolic BPV (SBPV), while wake after sleep onset (WASO) was an independent predictor of cfPWV, only. In addition, cfPWV showed a positive relationship with SBPV, and this relationship was moderated by sleep efficiency and WASO, respectively. The relationship between cfPWV and SBPV became stronger among individuals who had a level of sleep efficiency lower than 84% and who had WASO higher than 67 minutes, respectively.

Conclusions:
Our study showed that poor sleep not only had a direct link with arterial stiffness and BPV, but also moderated the relationship between these two subclinical CVD biomarkers. These findings implied that improving sleep quality could be a target intervention to promote cardiovascular health in clinical practice.
Abstract 14785: The Reactive Lipid Mediators Isolevuglandins Promote Atrial Fibrillation Mediated by Inflammation
Authors: Murphy Matthew B , Subati Tuerdi , Van Amburg Joseph C , Smart Charles D , Pitzer Ashley L , Kannankeril Prince J , Yang Zhenjiang , Stark Joshua M , Christopher Isis L , Kirabo Annet , Madhur Meena S , Barnett Joey V , Roden Dan M , MURRAY Katherine T
Published: May 2021

Introduction:
Inflammation and oxidative stress are linked to multiple risk factors for atrial fibrillation (AF), and to AF itself in the setting of sterile injury (e.g. after catheter ablation or cardiac surgery). However, anti-inflammatory therapies and conventional antioxidants cause adverse effects or are ineffective to prevent AF. Highly reactive mediators of lipid peroxidation such as isolevuglandins (IsoLGs) have been identified as a major component of oxidative stress-related injury. We hypothesized that during AF promoted by cardiac inflammation, a scavenger of IsoLG will decrease AF susceptibility.

Methods:
We studied mice with a systemic inflammatory phenotype due to deficiency in the lymphocyte adaptor protein (

Lnk
-/-

), a negative regulator of cytokine signaling. At weaning,

Lnk
-/-

mice and their wild-type (WT) littermates received either vehicle or a potent IsoLG scavenger, 2-hydroxybenzylamine (2-HOBA), by oral administration. At age 14 weeks, animals underwent transesophageal burst pacing, echocardiography, and tissue harvest or flow cytometry to measure atrial inflammation and IsoLG-adducts.

Results:
Cardiac histology and echocardiography revealed no major histologic or structural abnormalities in Lnk
-/-
mice. Nevertheless, Lnk
-/-
mice demonstrated a significant increase in AF burden compared to WT controls (124.8±43.3 vs 6.8±3 sec, respectively [mean±SEM, n=28, 12; P<0.05]), as well as increased sustained AF (> 30 sec; 48.1% vs 0%; P<0.01]). Leukocyte infiltration was present in the atria of Lnk
-/-
mice, with a significant increase in CD3, CD19, NK1.1, and CD11b/MHCII positive cells, compared to atria from WT control mice. Furthermore, there was a 2 to 4-fold increase in IsoLG-adducts for Lnk
-/-
atrial immune cells positive for CD3, CD19, NK1.1 and CD11b/MHCII, compared to cells from WT atria. Lnk
-/-
mice treated with 2-HOBA had significantly reduced AF burden (4.7±4.5 sec, n=7; P<0.05) with a trend towards reduction in sustained AF (0%, n=7; P=0.057).

Conclusions:
IsoLGs play a critical role in the pathogenesis of inflammation-mediated AF, and 2-HOBA, a scavenger of IsoLGs, represents a potentially novel therapeutic strategy for AF in this clinical setting.
Abstract 14794: Cmr-derived Biventricular Global Function Index is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot
Authors: ALSAIED Tarek , Geva Tal , Graf Julia , Sleeper Lynn A , Valente Anne M
Published: May 2021

Introduction:
Despite improvement in outcomes, patients with repaired tetralogy of Fallot (rTOF) are at risk for ventricular tachycardia and death. Cardiac magnetic resonance (CMR) derived global function index (GFI) is a new CMR parameter that integrates ventricular volume, mass, and function. This retrospective cohort study evaluated the utility of the biventricular global function index (BVGFI) for risk stratification in patients with rTOF.

Methods:
Patients with rTOF who had a CMR were followed for the occurrence of a composite outcome of death, resuscitated cardiac arrest, or sustained ventricular tachycardia (VT) were studied. GFI was calculated as the (ventricular stroke volume x 100) / (ventricular mean cavity volume + total ventricular myocardial volume). Ventricular mean cavity volume was defined as [(end-diastolic + end-systolic volume) /2]. BVGFI was calculated as the average of right and left GFI. Cox regression and CART analysis were used.

Results:
Of the 736 eligible patients (median age at CMR 25.4 years; median follow-up 28 months), 55 patients (7.4%) reached the composite outcome (41 deaths, 14 VT). Multivariable Cox regression identified BVGFI <37, RV end-systolic volume index >85 ml/m
2
, atrial tachycardia , and age at repair >2.5 years as independent predictors of outcome with a model C-index of 0.86. RVEF <40% , which is a known predictor of worse outcomes in previous studies, was not associated with the primary outcome when BVGFI is included in the analysis and only became significant when BVGFI was excluded from the model (C-index of 0.83). Similarly, CART analysis identified BVGFI as the only binary CMR parameter to identify patients at high-risk for adverse outcomes.

Conclusions:
We describe a novel CMR parameter that uses readily available parameters and is associated with adverse clinical outcome after adjusting for traditional CMR parameters in rTOF. BVGFI adds prognostic information and aids in risk stratification in the population.
Abstract 14803: Activin A Directly Impaired Human IPSC-cardiomyocyte Contractility and Electrophysiology
Authors: Megna Jake S , MacDonnell Scott , Ruan Qin , MORTON Lori G
Published: May 2021

Activin A is a homo-dimeric TGF-β family member involved in embryonic development, tissue morphogenesis, and cellular differentiation. Levels of activin A correlate with NYHA functional classification and age dependent cardiac dysfunction; however, no data are available to demonstrate a direct role for activin A in regulating human cardiomyocyte dysfunction. The purpose of this study was to characterize the functional impact of chronic activin A on human cardiomyocyte electrophysiology, contractility, calcium handling, and gene expression.

Methods:
Human iPSC-cardiomyocytes (iPSC-CM) were supplied by Fujifilm Cellular Dynamics. Calcium transients were captured using the FLIPR Tetra imager and impedance/electrophysiology by the Nanion CardioExcyte96. Cells were plated (50k/well), allowed to reach a stable synchronous monolayer, and dosed with 1nM of activin A (A) at each media change alongside a media control (C) or in the presence of inhibitory anti-activin A antibodies. Gene expression was determined using Taqman.

Results:
Activin A reduced contractile impedance amplitude (C=9.82±0.30, A=6.82±0.21 Ohms, p<0.01) and slowed relaxation velocity kinetics (C=48.78±2.65, A=35.07±1.07 Ohms/sec, p<0.01). Elongated extracellular field potential durations were observed with activin A treatment compared to control (C=0.49±0.02, A=0.56±0.01 sec, p<0.01). Impaired calcium handling peak amplitude (C=609±99, A= C=447±33 RFU, p<0.05) was also observed alongside slower calcium flux falling times (C=0.52±0.05, A=0.70±0.04 sec, p<0.01). An inhibitory activin-A antibody restored all parameters to control values. Chronic exposure of iPSC-CM to activin A reduced expression of calcium handling genes RYR2 (C=1.01±0.07, A=0.75±0.03, p<0.01) and ATP2A2 (C=1.00±0.05, A=0.89±0.05, p<0.05).

Conclusions:
Chronic activin A treatment reduced cardiomyocyte contractile amplitude, slowed contractile kinetics, impaired cardiomyocyte calcium handling, elongated the action potential, and reduced expression of genes regulating key calcium handling proteins. These data demonstrate that elevated levels of activin A can directly act on cardiomyocytes and therefore may contribute to cardiac dysfunction in heart failure and aged populations.
Abstract 14808: Acute Kidney Injury and Adverse Outcomes in Patients Undergoing Right Heart Catheterization versus Patients Undergoing Right and Left Heart Catheterization and Coronary Angiography
Authors: Min Annette , Roy Sumon , Wasilewski Melissa , Choxi Ravi , Perera Robert A , Jovin Ion S
Published: May 2021

Background:
Contrast induced nephropathy (CIN), or contrast-induced acute kidney injury is considered a complication of intravascular administration of iodinated contrast material. However, more recent studies have challenged the reported incidence of contrast nephropathy. We compared the incidence of acute kidney injury and of nephropathy at 3 months in patients undergoing only right heart catheterization (RHC) to patients undergoing right and left heart catheterization (R&LHC) and coronary angiography.

Methods and Results:
We studied 1779 consecutive patients at a Veterans Administration Medical Center, of which 869 underwent only RHC, which does not involve the administration of iodinated contrast media, and 910 patients who underwent R&LHC and coronary angiography. Creatinine values at 72 hours after the respective procedure were available in 938 patients and creatinine values at 3 months were available in 1246 patients. The incidence of acute kidney injury (defined as an increase in serum creatinine of 0.5 mg/dL or 25% compared to baseline) at 3 days was 34 (7.5%) in the RHC group and 46 (9.5%) in the R&LHC group (P=0.31). The incidence of nephropathy at 3 months was 89 (15.6%) in the RHC group and 113 (12.2%) in the R&LHC group (P=0.15). On multivariable analysis including adjustment for a propensity score, CIN at 3 days was not significantly associated with R&LHC (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.98-1.05; P=0.56) and neither was nephropathy at 3 months (OR 1.01, 95% CI 0.98-1.04; P=0.22). Patients undergoing R&LHC had a lower mortality at 12 months (hazard ratio 0.57, 95% CI 0.43-0.77; P<0.001).

Conclusions:
The incidence of acute kidney injury was not significantly different in patients undergoing RHC compared to patients undergoing R&LHC and coronary angiography, even though the former received no contrast dye. The incidence of nephropathy at 3 months was also not significantly different between the two groups while mortality was significantly lower in the group of patients undergoing R&LHC. This suggests that serum creatinine is a nonspecific diagnostic marker for contrast induced-kidney injury and that long-term outcomes are not associated with the administration of contrast in this population.
Abstract 14834: Protective Role of Cardiomyocyte-derived Ddt in Ischemic Cardiomyopathy
Authors: Ma Yina , Hu Xiaoyue , Pfau Daniel , Wu Xiaohong , Rao Veena , Testani Jeffery M , Margulies Kenneth B , Bucala Richard , Young Lawrence H
Published: May 2021

Background:
D-dopachrome tautomerase (DDT), the only homolog of macrophage migration inhibitory factor (MIF), is a cytokine highly expressed in cardiomyocytes and exerts autocrine-paracrine effects by signaling through the CD74 receptor. Endogenous DDT and MIF prevent acute ischemia-reperfusion injury and pressure overload-induced heart failure in mice. This study investigated whether endogenous cardiomyocyte DDT has a role in ischemic cardiomyopathy (ICM).

Methods:
LV tissue was obtained from patients with ICM during heart transplantation and from non-transplanted donor hearts. Plasma DDT concentrations were measured in heart failure outpatients with ICM. Cardiomyocyte-specific DDT knockout (cKO) and littermate control (CON) mice underwent MI or sham surgery. Serial echocardiography was performed to assess LV remodeling after MI or sham surgery. Tissue from the non-infarct region was analyzed 3 days and 4 weeks after MI or sham surgery for histology and molecular studies.

Results:
Cardiac DDT mRNA and protein expression were reduced in LV from patients transplanted for ICM (n=8). Plasma DDT concentrations below the median value were associated with worse survival in ICM outpatients (p<0.05, n=32). In mice, baseline LV function was similar in DDT cKO and CON after sham surgery and 3 days post-MI. However, DDT cKO mice developed more rapid LV dilatation and decreased LV ejection fraction and stroke volume as early as 1-week post-MI (n=4-6/group, all P<0.05). The DDT cKO mice had smaller cardiomyocyte cross-sectional area 4 weeks after MI (p <0.05), as well as early diminished phosphorylation of mTOR and S6-kinase (3 days post-MI). They also showed increased apoptosis 3 days post-MI and an early increase in p38 MAP kinase activation.

Conclusion:
Cardiomyocyte-derived DDT prevents adverse cardiac remodeling in ICM, potentially through modulating mTOR/S6 kinase (adaptive hypertrophy) and p38 MAP kinase (limiting apoptosis). Down-regulation of DDT in patients with ICM may contribute to the pathogenesis of advanced heart failure.
Abstract 14837: Social Determinants of Health and Outcomes in Patients With Advanced Heart Failure: Findings From PAL-HF
Authors: Blumer Vanessa , Rogers Joseph G , OConnor Christopher , Clare Robert M , Mark Daniel B , Fiuzat Mona , Granger Bradi B , Patel Chetan B , Samsky Marc D , Johnson Kimberly , Tulsky James , Mentz Robert J
Published: May 2021

Background:
Social determinants of health (SDH) are associated with cardiovascular disease outcomes, but the overall influence of SDH on end-stage heart failure has not been well-described.

Methods:
In the Palliative Care in Heart Failure (PAL-HF) study, 150 advanced HF patients were randomized to usual care or usual care plus palliative care intervention. In the present analysis, quality of life (QoL) metrics [Kansas City Cardiomyopathy Questionnaire (KCCQ) and Functional Assessment of Chronic Illness Therapy (FACIT) Palliative care (PAL)], anxiety and depression (Hospital Anxiety and Depression Scale; HADS Depression, HADS Anxiety) and clinical outcomes (mortality, rehospitalization) were examined based on SDH (marital status, employment status, economic security, education level). For statistical analyses, patients were grouped per independent variable of interest in dichotomous categories (partner vs. no partner, employed/retired vs. unemployed, patient-reported economic constraints vs. no constraints, education beyond high school (HS) vs. less than HS). Repeated measures models were used to compare QoL metrics between SDH groups and Cox models for clinical outcomes.

Results:
At 6-month follow-up, having a partner, being employed, education beyond HS, and having economic security were not associated with better QoL or anxiety/depression metrics in advanced HF patients. Unemployment and education less than HS were associated with increased 6-month rehospitalization (both p=0.03). SDH measures were not associated with mortality (all p>0.05) (Table).

Conclusions:
In this analysis of PAL-HF patients, SDH were not associated with improved QoL or anxiety/depression metrics over 6 months. However, being employed and education beyond HS were associated with reduced rehospitalization. Further studies accounting for SDH are needed to better determine how these factors should be incorporated into palliative care interventions in advanced HF.
Abstract 14842: Brain Fibroblast Growth Factor Receptor 4 Stimulation is Involved in High Phosphate Diet-Induced Skeletal Muscle Reflex Overactivation in Rats
Authors: Kim Han-kyul , Mizuno Masaki , Iwamoto Gary A , Ishizawa Rie , Mitchell Jere H , Pastor Johanne V , Moe Orson W , Smith Scott A , Vongpatanasin Wanpen
Published: May 2021

An increasing number of studies have reported a deleterious role of inorganic phosphate (Pi) in promoting hypertension. Previously, we have shown high Pi diet-induced excessive pressor and sympathetic responses to muscle contraction in otherwise normal rats, which were primarily mediated by an overactive exercise pressor reflex (EPR), a reflex arising from contracting muscle. However, the mechanism underlying these abnormalities generated by excess Pi intake remains unclear. Dietary Pi is known to increase release of bone-derived fibroblast growth factor (FGF) 23 to regulate Pi homeostasis. Evidence suggests that FGF23 and FGF receptors (FGFRs) are also present in the central nervous system. The aim of this study was to determine the role of brain FGFRs in mediating augmented EPR activity induced by dietary Pi excess. Accordingly, we assessed cerebrospinal fluid FGF23 levels in Sprague-Dawley rats fed either a normal 0.6% Pi diet (NP) or a high 1.2% Pi diet (HP) for 12 weeks. To determine the role of central FGFRs in mediating the EPR, we measured mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to hindlimb muscle contraction before and after intracerebroventricular (ICV) administration of either a selective FGFR4 inhibitor BLU9931 or a FGFR1/2/3 inhibitor AZD4547 in decerebrate NP and HP animals. Cerebrospinal fluid FGF23 levels were significantly higher in HP rats compared to NP rats (8.3±0.9 vs. 7.2±0.8 pM, P<0.01). ICV BLU9931 injection markedly attenuated (all P<0.01) the heightened MAP (Δ=41±14 vs. 20±14 mmHg) and RSNA (Δ=112±70 vs. 65±46 %) responses to EPR activation in HP animals, but did not significantly affect the responses in NP animals (ΔMAP=11±3 vs. 7±4 mmHg, ΔRSNA=21±17 vs. 15±5 %). MAP and RSNA responses to EPR stimulation were unchanged by ICV AZD4547 administration in NP or HP rats. In conclusion, our data demonstrate a novel action of central FGFR4 inhibition by reducing the high Pi diet-mediated skeletal muscle reflex overactivation. Importantly, the results implicate that activation of brain FGFR4 may lead to sympathetic dysregulation contributing to the abnormal hypertensive responsiveness after excess Pi consumption.
Abstract 14860: Echocardiographic Assessment of Shunt Fraction in Complex Cyanotic Heart Diseases Palliated With Aortopulmonary Shunts
Authors: Lee Joan K , olson briana , Jorgensen Neal , Files Matthew D
Published: May 2021

Introduction:
Neonates with complex heart defects with inadequate pulmonary blood flow require aortopulmonary shunts (APS) either as surgical-placed modified Blalock-Taussig shunt or a catheter-based stent implantation into a patent ductus arteriosus. An ideal APS provides equal pulmonary blood flow (Qp) as the systemic blood flow (Qs), which is considered balanced circulation. Pulmonary over-circulation leads to complications from inadequate systemic circulation, such as organ dysfunction, shock, and death. Accurately determining Qp:Qs ratio in these patients relies on catheterization, which is invasive and may falsely lower the Qp due to anesthetic effects. To our knowledge, there has not been any studies on echocardiographic comparisons of balanced versus overcirculated APS. We aim to evaluate echocardiographic Doppler assessment of velocity-time integral (VTI) at the aortic arch isthmus distal to APS origin as a measure of shunt fraction in APS patients. We defined shunt fraction ratio (SFR) as retrograde to prograde flow by VTI.

Methods:
This is a retrospective pilot study of neonates with APS. We selected two cohorts of patients with appropriately balanced circulation (n=12) and those with excessive Qp (n=5) resulting in end-organ damage. We analyzed serial echocardiograms, with repeated measurements for inter-observer agreement.

Results:
Mean SFR is lower in balanced cohort compared to the overcirculated cohort (0.45 ± 0.07 vs. 0.55 ± 0.09, p=0.02). For both groups, SFR was positively associated with oxygen saturation (r= 0.57, p=0.01), as well as markers of ventricular volume load, such as the highest brain naturetic peptide during hospitalization (Pearson’s correlation r=0.83, p= 0.04) and as outpatient (r= 0.72, p =0.02). Inter-observer agreement was 0.74, suggesting that this is a reproducible technique.

Conclusions:
SFR by VTI is a simple echocardiographic technique to estimate the volume of APS flow and appears to have important implications for clinical outcomes. Prompt characterization of pulmonary overcirculation without invasive assessment could improve clinical management. Further prospective studies are needed to validate these findings.
Abstract 14867: Atrial Fibrillation is Associated With Risk of Incident Heart Failure and Its Subtypes
Authors: Nicoli Charles D , O'Neal Wesley T , Levitan Emily B , Singleton Matthew J , Judd Suzanne E , Howard George , Safford Monika M , Soliman Elsayed Z
Published: May 2021

Background:
Heart failure (HF) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for HF and its subtypes in a racially diverse population is unclear.

Methods:
This analysis included 25,787 participants free of baseline HF from the REasons for Geographic And Racial Differences in Stroke (REGARDS). AF at baseline was identified by electrocardiogram and self-reported physician diagnosis. HF events during follow-up were ascertained from medical records with subclassification by left ventricular ejection function (EF) at time of diagnosis as HF with reduced EF (HFrEF; EF<40%), HF with preserved EF (HFpEF; EF≥50%), mid-range HF (EF 40-49%) and unclassified. Cox proportional-hazards regression was used to separately examine the association of baseline AF and incident overall HF, HFpEF, and HFrEF. The Lunn-McNeil method was used to test differences in the association of AF by HFrEF & HFpEF. Consistency of the associations of AF with HF and its subtypes was examined in subgroups stratified by sex and race.

Results:
AF was detected in 1,924 (7.5%) participants at baseline (2003-2007). Over 10.1 years median follow-up, 1,109 HF events occurred (388 HFrEF, 356 HFpEF, 77 mid-range HF, and 288 unclassified). AF was associated with more than 2-fold increased risk of overall HF as well as its subtypes HFpEF and HFrEF in models adjusted for socio-demographics and cardiovascular risk factors. The strength of associations was slightly attenuated after adjustments for Warfarin, aspirin and statin. A stronger association of AF with HFrEF than HFpEF was observed, but the difference was not statistically significant. These associations were consistent among men, women, Black and White subgroups (Table).

Conclusions:
AF is strongly associated with both HFrEF and HFpEF. While further investigation of the underlying mechanisms is needed, our findings extend the sequelae of AF beyond stroke to include HF regardless of type.
Abstract 14879: Heart Failure With Preserved Ejection Fraction Patients Do Not Augment Longitudinal Pumping During Exercise
Authors: Macnamara James P , Tayon Kevin , Cornwell William K , Howden Erin , Hieda Michinari , Lawley JUstin , LEVINE Benjamin D , Sarma Satyam
Published: May 2021

Introduction:
Left ventricular (LV) pumping from longitudinal motion is highly efficient and a major contributor to stroke volume (SV). Patients with heart failure with preserved ejection fraction (HFpEF) have diminished longitudinal ventricular motion but the effect on LV pumping is unknown. This study aimed to determine the contribution of longitudinal pumping in HFpEF compared to healthy age-matched controls at rest and submaximal exercise when exercise induced SV reserve is maximal.

Methods:
Cardiopulmonary exercise testing with concurrent 3D echocardiography was performed in 30 subjects (HFpEF n = 20, age 69±5 years, Senior Control (CON): n = 10, age 70±4 years) at rest and during exercise at a targeted heart rate of 100 bpm (HFpEF 66±18% VO
2
Max, CON: 49±13% VO
2
Max, p = 0.014). LV volumes and mitral annular excursion (MAE), a novel metric of systolic function, were measured using multi-beat 3D acquisition at rest and during sub-maximal exercise. MAE volume (MAEV) was measured by multiplying MAE by short axis area at the base of the ventricle. Relative longitudinal pumping was calculated as the quotient of MAEV and SV (%).

Results:
Mitral annular excursion (MAE) at rest was lower in HFpEF
(Figure)
and increased significantly less during sub-maximal exercise compared to controls (CON Δ3.3mm vs HFpEF Δ1.1mm, group p = 0.002, group x exercise p = 0.011). MAEV was similar in HFpEF compared to controls at reest but did not augment in HFpEF compared to controls (CON Δ7.1 ml vs HFpEF Δ1.9 ml, group x exercise p = 0.002). Relative longitudinal pumping increased significantly with exercise in CON but remained unchanged in HFpEF (CON Δ7.9% vs HFpEF Δ-0.7%, group x exercise p = 0.043).

Conclusions:
Longitudinal pumping does not increase in HFpEF patients despite exercising at a higher relative metabolic demand than their healthy peers. This lack of longitudinal pumping reserve may contribute to and help identify cardiac limitations during exercise commonly seen in HFpEF patients.
Abstract 14881: Impact of a Large-scale Telemedicine Network on Emergency Visits and Hospital Admissions During the Covid-19 Pandemic in Brazil: Data From the UNIMED-BH System
Authors: Nascimento Bruno R , Castro Ana Cristina T , Fróes Luiz Eduardo V , Ribeiro Antonio L , Araújo Cynthia B , Souza Charles F , Fróes Eduardo T , Brant Luisa C , Souza Soraya D
Published: May 2021

Introduction:
A strategy for healthcare surge control in the Covid-19 pandemic is forward triage by on-demand telemedicine (TM), implemented by several providers. We aimed to evaluate the impact of a large-scale Covid-19 TM system on visits to emergency medical services (EMS) and all-cause and cardiovascular (CV) hospital admissions during the pandemic in Brazil.

Methods:
From March 18 - May 18, 2020 we evaluated the database of UNIMED-BH, a cooperative Brazilian private health insurance, with over 1.25 million clients. The Covid-19 TM system consisted of: a) online mobile app with questions about Covid-19 symptoms, which redirects to teleconsultations in case of moderate/severe manifestations; b) telemonitoring system, with regular phone calls to all clients with reported flu-like symptoms or Covid-19 diagnosis, to monitor disease progression; c) 24/7 emergency call and ambulance system (GMOV), with VOIP triage and counselling by 2 physicians: calls with suspected Covid-19 or respiratory abnormalities were computed. EMS visits and admissions in all accredited hospitals were recorded, with diagnoses assessed by the Diagnosis Related Groups (DRG) method. Covid-19 lab diagnosis and deaths were identified from the patients’ registries, and outcomes assessed until June 1
st
.

Results:
In 60 days, 24,351 patients (1.9% of clients) accessed one of the TM systems, 59% women, median age was 35±18 years. The most frequently utilized system was telemonitoring (16,717, 69%), followed by teleconsultation (13,350, 55%) and GMOV (683, 3%); 6,330 patients accessed multiple systems. The rates of EMS and hospital admissions for each system were: telemonitoring 19.7% (3,296) and 4.6% (774); teleconsultation 17.3% (2,312) and 2.3% (311) and GMOV: 55.9% (382) and 56.2% (384) patients. At total 4.1% (996) had at least 1 hospital admission, 32% (321) with respiratory diseases (41 requiring mechanical ventilation) and 5.6% (56) with CV diagnoses (12 acute coronary syndromes). Overall, 277 (1.1%) patients had confirmed Covid-19 diagnosis, and 160 (0.7%) died, 9 with Covid-19.

Conclusion:
The TM system resulted in low rates of EMS visits and hospital admissions, suggesting a positive impact on healthcare utilization. The percent of admissions due to CV causes was low.
Abstract 14885: E/e’ Does Not Consistently Track Left Atrial Pressure When Venous Return is Altered
Authors: Macnamara James P , Koshti Vivek , Howden Erin , Lawley JUstin , Hearon Christopher , Dias Katrin , Sarma Satyam , LEVINE Benjamin D
Published: May 2021

Introduction:
The E/e’ ratio is often used as a surrogate for left atrial pressure (LAP) despite concerns about reliability and accuracy when LAP is sequentially changed within individuals. This study tested how E/e’ tracks linearly with LAP with the aim of determining if invasive markers of diastolic function are associated with better tracking.

Methods:
Healthy subjects (n = 61, age 52±5 years) underwent manipulation of LAP with 2 levels of lower body negative pressure (LBNP -15 mm Hg, -30mm Hg) and 2 levels of rapid normal saline infusion (NS +15 mL/kg/min, +30 mL/kg/min) with a right heart catheter and echocardiography to define the LV end-diastolic pressure-volume relationship. E/e’ and pulmonary capillary wedge pressure (PCWP) were measured at each condition. Myocardial stiffness was calculated by the slope of the LV pressure-volume curve. LV relaxation was assessed with Tau: (Isovolumetric relaxation time/(ln(Systolic Blood Pressure x 0.9)-ln(PCWP)). R
2
of individual regressions of E/e’ and PCWP for each subject was used to determine quality of tracking across loading conditions.

Results:
PCWP ranged from 5 mm Hg to 20 mm Hg across loading conditions (p <0.001). As a group, E wave velocity demonstrated a consistent linear relationship with PCWP while e’ was more variable
(Figure)
. The mean r
2
of individual regressions was 0.50 ± 0.29 with a high coefficient of variation of 57.1%. Higher baseline PCWP, myocardial stiffness or longer LV relaxation were not associated with improved tracking (p = 0.96, p = 0.55, p = 0.62 respectively).

Conclusion:
This study, the largest cohort to date with experimental altered LAP, highlights the difficulty assessing E/e’: As a cohort, E/e’ tracked with PCWP moderately well, but there was significant variation on an individual level which was independent of baseline LV filling pressure, stiffness and relaxation. Caution should be used when interpreting E/e’ as LAP in healthy individuals even with abnormalities in diastolic filling.
Abstract 14887: Look Beyond the Coronaries: A Rare Cause of Acute Papillary Muscle Rupture
Authors: Kagan Calvin M , Kenigsberg Benjamin , WEISSMAN Gaby , Hofmeyer Mark , Najjar Samer S , Krishnan Jayashree , Barnett Christopher
Published: May 2021

A 63-year-old male with numerous cardiac risk factors presented with two hours of rapidly progressing chest pain and shortness of breath. Exam was notable for respiratory distress requiring non-invasive mechanical ventilation and a holosystolic apical murmur radiating to the axilla. He had an elevated troponin and an electrocardiogram with anteroseptal ST depressions. He was diagnosed with a non-ST segment elevation acute coronary syndrome and taken for cardiac catheterization. Surprisingly, no occlusive epicardial disease was discovered. Left ventriculogram revealed engorgement of the left atrium and pulmonary arteries suggestive of severe mitral regurgitation. The mechanism of mitral regurgitation was unclear until transesophageal echocardiography showed a ruptured posteromedial papillary muscle with flail mitral valve, a picture classically caused by myocardial infarction. Cardiac MRI demonstrated preserved LV function with minor inferior apical hypokinesis, nonspecific endocardial late gadolinium enhancement in the inferior segments, and a small LV thrombus. An embolic myocardial infarction targeting a small territory involving posteromedial papillary muscle was thought most probable. The patient then underwent an uneventful mitral valve replacement and recovery. However, he returned two months later with severe biventricular dysfunction and cardiogenic shock with peripheral eosinophilia. Myocardial biopsy confirmed the diagnosis of eosinophilic myocarditis. An exhaustive workup for the etiology of his eosinophilia proved unrevealing; he was consequently diagnosed with the idiopathic subtype. The case highlights a rare but important clinical entity that has a varied phenotype. Our patient presented atypically with an acute papillary muscle rupture that mimicked an acute myocardial infarction, ultimately delaying diagnosis. As evidenced by our case, clinical suspicion of myocarditis should be high in all patients presenting with typical anginal symptoms with mechanical or circulatory compromise in the absence of acute coronary occlusion.
Abstract 14890: Diagnosing Duchenne Muscular Dystrophy-Associated Cardiomyopathy: Echocardiogram Shoots, Cardiac Magnetic Resonance Imaging Scores
Authors: Sheth Rahul , Ramaciotti Claudio , Araj Faris G , Cheeran Daniel , Amin Alpesh A , Drazner Mark H , Peshock Ronald M , Mammen Pradeep P
Published: May 2021

Background:
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder characterized by progressive muscle degeneration. The leading cause of death is complications from the development of DMD-associated cardiomyopathy. The majority of DMD patients have skeletal abnormalities that limit the quality of echocardiograms (ECHO). Although cardiac magnetic resonance imaging (cMRI) is the gold standard cardiac imaging tool, the vast majority of DMD patients are evaluated by ECHO rather than cMRI. We hypothesized that when compared to ECHO, cMRI more accurately assesses cardiac function and provides more valuable data for the diagnosis of DMD-associated cardiomyopathy.

Methods:
We undertook a retrospective study of 20 DMD patients referred to the UT Southwestern Adult Neuromuscular Cardiomyopathy Clinic who had undergone both an ECHO and cMRI within 15 months of each other. We assessed the proportion of studies demonstrating reduced left ventricular (LV) function [cMRI LVEF<62%, ECHO fractional shortening (FS)<25%] and that were technically difficult by both techniques. In addition, we assessed the proportion of cMRIs with late gadolinium enhancement (LGE), a marker of myocardial fibrosis and associated with increased mortality.

Results:
Amongst these patients, 10% of cMRIs and 85% of ECHOs were technically difficult. By cMRI, 30% of the studies were normal (LVEF 64±2 %), while 70% showed reduced function (LVEF: 44±12%). By ECHO, 75% of the studies were normal (FS 32±5), while 25% showed reduced function (FS: 15±8). Of the patients with truly reduced function by cMRI, 64% were considered normal by ECHO. Finally, 61% of cMRI studies showed LGE (50% with normal LVEF and 67% with reduced LVEF).

Conclusions:
In summary, cMRI is superior to ECHO in assessing cardiac function in DMD. ECHO underestimates left ventricular dysfunction, likely due to the poor quality of studies obtained in this patient population. In addition, cMRI identifies LGE, a marker associated with increased mortality, irrespective of cardiac function. Earlier utilization of cMRI will expedite the diagnosis of DMD-associated cardiomyopathy and enable the cardiologist to initiate aggressive guideline-directed medical therapy at an earlier age.
Abstract 14892: Mobile Technology Improves Adherence to Cardiac Rehabilitation: A Propensity Score-matched Study
Authors: Imran Tasnim F , Wang Na , Zombeck Stephanie , Balady Gary J
Published: May 2021

Objective:
To examine whether mobile technology improves adherence to cardiac rehabilitation and other outcomes.

Methods:
We identified enrollees of the cardiac rehabilitation program at Boston Medical Center from 2016-2020 (n=830). Some enrollees used a mobile technology application (Wellframe.com) that provided a customized interactive list of educational content in a progressive manner, used the patient’s smart phone accelerometer to provide daily step counts, and served as a two-way messaging system between the patient and the program staff. Adherence to cardiac rehabilitation was defined as the number of attended prescribed sessions and completion of the program. To evaluate change in the following: exercise capacity, Beck Depression Index (BDI) scores, weight, quality of life scores and Rate Your Plate nutrition scores, we used the generalized estimating equation method.

Results:
After 2:1 propensity score matching for age, sex, race, education, smoking status, transportation time to cardiac rehabilitation center, qualifying diagnosis, and baseline BDI score, there were 121 enrollees in the group using the Wellframe application as a supplement to the rehabilitation program and 280 enrollees in the Standard rehabilitation group. Enrollees had a mean age of 59 years; 32% were women, and 42% were black. Those in the mobile technology group attended a higher number of prescribed sessions (mean 28 vs. 22), RR: 1.17 (95% CI: 1.04-1.32, p=0.009), were 1.8 times more likely to complete the cardiac rehabilitation program (p=0.01), and had a slightly greater weight loss (lbs) post rehabilitation: -1.71 (95% CI: -0.30, -3.11, p=0.02) as compared to those in the Standard group; other outcomes were similar between the groups (Table 1).

Conclusion:
In a propensity-matched, racially diverse population, we found that adjunctive use of mobile technology significantly improved adherence to cardiac rehabilitation and number of attended sessions.
Abstract 14893: Light Activation in Plaque Macrophages Enhances Efferocytosis of Apoptotic Cells via Upregulation of Autophagy and Mertk Expression
Authors: Song Joon Woo , Lee Min Woo , Kim Hyun Jung , Min Jiseon , Kang Un Gyo , Kim Yeon Hoon , Han Jeongmoo , Yoo Hongki , Park Kyeongsoon , Kim Jin Won
Published: May 2021

Introduction:
Autophagy plays a protective role in atherosclerosis and can promote efferocytosis of apoptotic cells. Photoactivation is a promising tool for treating cardiovascular disease, and induces autophagy in macrophages-derived foam cells, however, regulation of autophagy and efferocytosis by photoactivation in atherosclerotic plaque remains unknown.

Objective:
The present study aims to investigate whether macrophage targeted light activation induces autophagy and enhances efferocytosis in inflamed plaques

Methods and Results:
Targeted photoactivatable agent showed specific binding affinity and phototoxicity to scavenger receptor-expressing macrophages. Confocal microscopy analysis over time after irradiation demonstrated the induction of apoptosis and autophagy flux in macrophage-derived foam cells. The theranostic agent localized to macrophage scavenger receptors within atherosclerotic plaques, and intravital fluorescence microscopy imaged plaque inflammation and was used to monitor photobleaching after irradiation. Serial in vivo imaging analysis demonstrated that macrophage-specific photoactivation reduced plaque burden and inflammation after 1 week (Figure A). Mechanistically, targeted light activation induced autophagy within atheroma as early as 1 day (Figure B), and increased phagocytic receptor Mer tyrosine kinase (MerTK) expression. Targeted photoactivation had 2-fold-increase in macrophage-associated apoptotic bodies at one week after laser irradiation, indicating enhanced efferocytosis (Figure C).

Conclusions:
As a sensitive multifunctional therapeutic and imaging strategy, macrophage targeted photoactivation with autophagy induction could confer a promising theranostic strategy for the high-risk plaques.
Abstract 15077: Serum-transthyretin: Does it Predict Ablation Outcome in Patients With Atrial Fibrillation?
Authors: Mohanty Sanghamitra , TRIVEDI CHINTAN G , Gallinghouse Joseph , Della Rocca Domenico G , Gianni Carola , MacDonald Bryan , Mayedo Angel , Baqai Faiz , Bai Rong , Bassiouny Mohamed , Burkhardt John , Horton Rodney , Al-ahmad Amin , Natale Andrea
Published: May 2021

Background:
Transthyretin (TTR), a transport protein produced by liver, is closely associated with amyloidosis. Tetramers of TTR circulating in blood can dissociate to monomers that misassemble into amyloid fibrils. Although amyloidosis is a frequent finding in aged atrial fibrillation (AF) patients, the relevance of serum-TTR in AF is unknown.

Objective:
We evaluated if post-ablation change in serum-TTR level has any prognostic association with long-term ablation outcome in AF patients.

Methods:
One-hundred-forty-five patients (age: 62.8 ± 6.2years, male 69%, non-paroxysmal AF 41%, BMI : 30.8 ± 6.3) were included in this prospective study. Patients with chronic inflammatory conditions or taking anti-inflammatory drugs were excluded. All patients received pulmonary vein isolation plus isolation of left atrial posterior wall and superior vena cava. In non-paroxysmal AF, non-PV triggers identified by isoproterenol challenge were ablated. Fasting blood samples were collected at baseline and 24-hours post-ablation. Samples were tested for
TTR
using an automated quantitative test.

Results:
Mean TTR concentration was 27.94±6.5 mg/dL at baseline and 26.33±9.2 mg/dL at 24-hour post ablation (p<0.001). Of the 145 patients, post-ablation TTR remained unchanged or increased in 65 (44.8%) and decreased in 80 (55.2%) patients at 24-hour post-ablation. Mean decrease in the serum TTR in these 80 patients was 7.9± 4.38 mg/dL. At 3 years of follow-up, the recurrence rate was 28/80 (35%) in the group with decreased-serum TTR and 11/65 (17%) in the population with unchanged/increased TTR (p=0.01). Post-ablation decrease in TTR was found to be an independent predictor of recurrence (OR 2.64 (1.19-5.85), p=0.01).

Conclusion:
Our findings demonstrated significant association of higher recurrence rate with decreased serum-TTR tetramer level at 24-hour post-ablation.
Abstract 15078: Non-selective but Not Selective His Bundle Pacing Uniquely Resolves Acute and Chronic Right Bundle Branch Block
Authors: Mahmud Rehan , Jamal Shakeel , Bailey Bdeth
Published: May 2021

Introduction:
While acute (Ac) right bundle branch block (RBBB) may be in proximal HB (lead fixation injury) and chronic (Ch) RBBB in distal HB, they both cause
terminal
QRS delay. Both types of RBBB may be corrected with non-selective (NS) His bundle pacing (HBP), however the mechanism is unknown.

Hypothesis:
To study the role of high (5V) and low (1V) pacing voltage as well as presence of pre-excitation (in NS-HBP) in resolving Ac and chronic Ch-RBBB.

Methods:
Of the thirty-nine patients (27 ChRBBB and 12 AcRBBB), 25 ChRBBB and 10 AcRBBB patients showed NS-HBP at 5V and 11/25 ChRBBB and 6/12 AcRBBB patients transitioned to selective (S)-HBP at 1V. Four patients showed S-HBP at 5V and 1V.

Results:
1)During NS-HBP at 5V: (In 25 ChRBBB and 10 Ac-RBBB) Complete resolution occurred 12/25ChRBBB and in all 10 AcRBBB. A partial resolution of ChRBBB occurred 13/25 ChRBBB.2.
During NS-HBP at 1V:
(6/14 ChRBBB and 2/4 AcRBBB showed complete resolution at 1V, remainder showed incomplete RBBB3.
During S-HBP at 5V
: (2 ChRBBB 2 AcRBBB) only 1 AcRBBB showed resolution of RBBB. 4.
During S-HBP at 1V
: All 13 ChRBBB and 8 AcRBBB did not show resolution os RBBB including 11 Ch-RBBB and 6 Ac-RBBB RBBB which resolved during 5V NS-HBP, abruptly recurred on transition to S-HBP at a mean of 2.4±0.8V.

Conclusions:
1)The lack of RBBB resolution with S-HBP suggests that pacing site was proximal to site of block, however, from the same site NS-HBP either completely or incompletely resolved both Ac- and Ch-RBBB. 2) Partial resolution of RBBB in NS-HBP may be explained by right ventricular free wall pre-excitation when site of Ch-RBBB is distal.3) Complete resolution of both acute and Ch-RBBB in NS-HBP, more so at high pacing voltage, suggest that peri-Hisian tissues may behave more like a specialized conduction tract which uniquely resolves conduction block.
Abstract 15079: Equitable Access to MHealth Through a Smartphone Loaner Program in Patients With Acute Myocardial Infarction
Authors: Yang William E , Spaulding Erin , Shah Lochan , Hung George , Vervoort Dominique , Ding Jie , Marvel Francoise A , Martin Seth S
Published: May 2021

Introduction:
Mobile health (mHealth) is expanding as a healthcare delivery tool but depends on patients’ existing ownership of technology, which could create inequity. We faced this challenge in developing and implementing the “Corrie” mHealth program for Apple iOS and watchOS to aid patients in post-myocardial infarction recovery. Considering that cardiologists commonly loan equipment to patients (e.g. Holter monitors), we created an iPhone loaner program to expand access to Corrie. Here, we explore sociodemographics and readmission outcomes associated with loaner use.

Methods:
In the Myocardial infarction COmbined-device Recovery Enhancement (MiCORE) study, we prospectively enrolled acute myocardial infarction patients at four hospitals. Patients who owned a compatible iPhone used Corrie on their own phone (“non-iShare”) while others used a loaner iPhone (“iShare”). Loaned phones were returned 30 days after discharge. We used logistic regression models to evaluate sociodemographic differences in iShare versus non-iShare patients. We also explored readmission outcomes in the two groups.

Results:
Of the 200 patients in MiCORE, 46% (n=92) were in the iShare group. Compared to non-iShare patients, iShare patients were younger (mean age 57.4±11 years [range 30-81] vs 60.8±11 [32-89]; p=0.04). After adjusting for age, iShare patients were more likely to be women (36% vs 23%, p=0.03), insured by Medicaid (20% vs 4%, p<0.01), and less likely to have commercial insurance (47% vs 61%, p<0.01). More iShare patients were black (25% vs 14%), unmarried (49% vs. 35%) and unemployed/disabled (29% vs 16%) relative to non-iShare patients, albeit not reaching statistical significance (p>0.05). Among patients asked about income (53%, n=106), iShare patients had a lower mean annual income ($56,000 vs. $97,000, p<0.01) and a higher percentage of annual income <$30,000 (35% vs 11%, p<0.01). Readmissions were infrequent and similar in iShare and non-iShare patients, including 30-day all-cause readmission (10% vs 4%, p=0.09) and cardiac readmission (4% vs 2%, p=0.66).

Conclusions:
These results suggest the potential for a smartphone loaning program to facilitate equitable mHealth access for underserved patients including those with a lower income.