bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12618: Human And Mouse Demonstration Of The Reticulum-Mitochondria Ca
2+
Coupling As A New Therapeutic Target In Metabolic HFpEF
Authors: Dia Maya , Guedouari Hala , Geoffray Juliette , CHERPAZ Maelle , Pozzi Matteo , Leon Christelle , Chanon StÃ©phanie , Bendridi Nadia , Gomez Ludovic , Rieusset Jennifer , Thibault Helene , Paillard Melanie
Published: June 2023

Context:
Metabolic heart failure with preserved ejection fraction (HFpEF) is a frequent and disabling disease with yet no therapy and limited knowledge on the cardiac underlying molecular mechanisms. Ca
2+
transfer at mitochondria-associated reticular membranes (MAM) is crucial in the cardiomyocyte to tightly regulate mitochondrial Ca
2+
content and assure the excitation-energetics coupling. We aimed to specify the role of the MAM Ca
2+
coupling in both human and mouse hearts with metabolic HFpEF.

Results:
Mass spectrometry analysis of cardiac MAM showed an upregulation of cellular response to stress and lipid metabolism processes in two obesogenic T2D mouse models (16 weeks of high-fat high-sucrose diet, HFHSD vs standard diet, SD; 12-week old leptin-deficient ob/ob vs WT), while Ca
2+
transport was downregulated only in the HFHSD MAM. MAM Ca
2+
coupling assessment by adenoviral infection of a FRET-based mitochondrial Ca
2+
sensor, revealed a MAM Ca
2+
uncoupling in the HFHSD cardiomyocyte, leading to reduced mitochondrial Ca
2+
content and bioenergetics, while no change was measured in the ob/ob cell. HFHSD mice exhibited cardiac hypertrophy, diastolic dysfunction and mild strain rate reduction with preserved EF. Ob/ob mice only displayed strain rate reduction and concentric hypertrophy. Principal component analysis (PCA) demonstrated a divergence between the HFHSD group and the three others, as displayed by their scattering along the first PC (61% of variance) contributed mainly by strain rate, wall thickness, body weight and Ca
2+
peak amplitude. Proximity ligation assay revealed a decreased proximity between the reticular IP3-receptor and the mitochondrial porin VDAC in human left ventricle biopsies from T2D versus non-diabetic patients, obtained during valve replacement surgery: this suggests a reduced formation of the IP3R-driven Ca
2+
channeling complex.

Conclusion:
The ob/ob model does not recapitulate the main hallmarks of metabolic HFpEF and does not display any change in MAM Ca
2+
coupling. On the contrary, a MAM Ca
2+
uncoupling was detected both in the human T2D heart and in the heart of the HFHSD-induced metabolic HFpEF mouse, suggesting the reticulum-mitochondria Ca
2+
coupling as a critical therapeutic target in metabolic HFpEF.
Abstract 12632: Relationships Between Circadian Ambulatory Systolic Blood Pressure Variability With Subclinical Atherosclerosis in Healthy Middle-Aged Individuals
Authors: TSE YIU-HEI , HSU Matthew , Pijarnvanit Kong Kam Tim Siriphong , CHEUNG Carman Nga-Man , Chow Yick Hin , KOT Brian C. W. , Tse Hung-Fat , Lau Kui Kai
Published: June 2023

Background:
Short-term fluctuations in blood pressure (BP) as measured by 24-hr ambulatory BP monitoring (ABPM) is associated with subclinical atherosclerosis in the general population. However, whether short-term blood pressure variability (BPV) in the day versus night-time has differential effects on the development of subclinical atherosclerosis is uncertain.

Methods and Results:
We investigated the relationship between mean 24-hr BP and BPV parameters with common carotid artery intima-media thickness (CIMT) in 305 middle-aged Chinese (mean age 54±7years, 45% male) free from hypertension, hyperlipidaemia, diabetes or cardiovascular diseases. Subclinical atherosclerosis with elevated CIMT was defined as >75th percentile of CIMT of the overall study cohort. Linear regression models adjusted for age, sex, body mass index and smoking status revealed significant associations between office, day- and night-time mean SBP, day-time SBP standard deviation (SD) and coefficient of variation (CV) with elevated CIMT (all p<0.05). As shown in the
Table
, logistic regression analysis demonstrated that only ABPM day-time mean SBP (odds ratio [OR]:2.54, 95% confidence interval [95%CI]:1.29-5.00), night-time mean SBP (OR:3.23, 95%CI:1.67-6.22), night-time mean DBP (OR:2.27, 95%CI:1.16-4.42), day-time SBP CV (OR:0.47, 95%CI:0.26-0.86) and night-time SBP SD (OR1.94, 1.05-3.58) predicted the occurrence of subclinical atherosclerosis (all p<0.05).

Conclusions:
In healthy middle-age individuals without known hypertension, mean day and night-time SBP as measured using ABPM provided the strongest positive predictive value for elevated CIMT. Interestingly, increase day-time SBP CV versus night-time SBP SD have opposite effects on CIMT, suggesting circadian changes in SBP might have distinct contributions to the development of subclinical atherosclerosis.
Abstract 12633: Factors Affecting Quality of Life Among Patients With Hypertrophic Cardiomyopathy
Authors: Oh YiRae , Hong Geu-Ru , Choi JiYeon , Chu Sang Hui
Published: June 2023

Background:
Hypertrophic cardiomyopathy (HCM) is the most common genetically determined chronic condition with various clinical symptom and course. Recently, illness perceptions have been known to influence mental health outcomes in patients with HCM. However, limited studies exist on HRQoL and its determinant factors including psychosocial components in patients with HCM. This study aimed to identify factors affecting HRQoL in patients with HCM.

Methods:
A total of 101 patients with HCM (mean age, 59±12 years; men,74.3%; obstructive type, 43.6%) participated in the study at their regular visits to the outpatient clinic of a university affiliated hospital in Seoul, from July to December, 2020. A questionnaire including the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) as a measure of physical and mental HRQoL, Korean Illness Perception Questionnaire, Health Promoting Lifestyle II, Patient Health Questionnaire-9 (PHQ-9), and Korean activity scale index (KASI) was used. Multivariable linear regression analysis was conducted to assess determinants of HRQoL.

Results:
The mean physical component score (PCS) of HRQoL was 47.15±7.66 and mental component score (MCS) was 51.41±8.61. Lower physical functional capacity (β=-.398, p<.001) and higher cyclical timeline beliefs of illness perception (β=-.230, p=.039) were independently associated with lower PCS with 35.9% explanatory power (p<.001). Women (β=-.218, p=.032), depression (β=-.307, p=.004), and stress management (β=.240 p=.042) were identified as independent predictors of MCS with 39.7% explanatory power (p<.001).

Conclusions:
This study shows the important role of illness perception in determining the physical HRQoL in patients with HCM. Interventions aimed at changing Illness perception and reducing depression may be promising approaches to improve HCM patients’ HRQoL.
Abstract 12647: Acute Glucocorticoid Receptor Activation Induces Rat Heart Cardioprotection Against Infarction Through Na+/h+ Exchanger Regulation
Authors: Escudero Daiana S , Fantinelli Juliana C , Amarillo Maria E , Perez Nestor G , Diaz Romina G
Published: June 2023

Introduction:
Acute corticosteroid therapy has been used in the prophylaxis against atrial fibrillation following cardiac surgery or acute myocardial infarction (AMI). Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue. While MR activation during AMI was linked to Na
+
/H
+
exchanger (NHE1) activation-mediated increase in infarct size and contractile dysfunction, lesser is known about GR effects. The aim of this work is to seek the functional effects of an acute dose of a low potency corticosteroid (hydrocortisone, HC) in a rat model of AMI.

Methods:
AMI was promoted in isolated hearts from Wistar rats by 40min of regional ischemia followed by 60min reperfusion (ischemic control “I”, n=4). 10nM HC (HC10, n=3) or HC10 plus the GR inhibitor Mifepristone (M, 10uM, n=5) was added to the perfusate during the first 10min of reperfusion. In isolated papillary muscles from non-infarcted hearts NHE1 activity was measure by analyzing the pH recovery from an acute transient acidosis (TA) in control conditions, and in the presence of HC 1nM (HC1) or HC10. Protein phosphorylation and expression were determined by western blot. Data are expressed as mean±S.E.M.

Results:
HC treatment reduced infarct size (% of risk area: 38±3 I; 9±3 HC10, p<0.05, t-test), improved left ventricular developed pressure, LVDP (% of preischemic control: 28±4 I vs. 60±5 HC10, P<0.05, t-test) and decreased left ventricular end diastolic pressure, LVEDP (in mmHg: 55±4 I vs. 28±5 HC, P<0.05, t-test). M avoided HC protective effects (infarct size 24±4%; LVDP 34±10%; LVEDP 10±2 mmHg). HC reduced NHE1 activity (JH+ in mmol/ml/min: 1.22±0.19 TA, n=5; 0.68±0.11 HC1, n=4; 0.56±0.15 HC10, n=4, p<0.05, ANOVA). Neither NHE1 expression nor the NHE1 pro-activating Ser703 phosphorylation were modified. HC10 increased NHE1 pro-inhibiting Ser648 phosphorylation (% of control: 102±7 TA, 111±16 HC1, 155±23 HC10, n=8, p<0.05, ANOVA). In line, AKT phosphorylation level was increased by HC (% of control: 102±18 TA, 160±20 HC1, 202±24 HC10; n=9, p<0.05, ANOVA).

Conclusions:
Our results show that HC induce cardiac protection against AMI via GR activation, through a mechanism that may be assigned to an inhibitory AKT-mediated Ser648 NHE1 phosphorylation.
Abstract 12664: Comprehensive Histological Analysis of Endomyocardial Biopsy and T1 Mapping for Predicting Left Ventricular Reverse Remodeling in Patients with Recent-Onset Dilated Cardiomyopathy
Authors: Ida Mizuki , Nakamori Shiro , Ishiura Junko , Ito Rie , Ishida Masaki , Fujimoto Naoki , Okamoto Ryuji , Imanaka-yoshida Kyoko , Sakuma Hajime , Dohi Kaoru
Published: June 2023

Background:
Cardiomyocyte injury is a key pathological pathway in the progression of heart failure that predicts a poor prognosis; therefore, combined assessment of myocardial fibrosis and cardiomyocyte DNA damage from endomyocardial biopsy (EMB) samples may be of great importance. Meanwhile, cardiovascular magnetic resonance (CMR) native T1 reflects a composite of both intra- and extracellular compartments in the whole myocardium. We sought to assess the performance of native T1 mapping and EMB results to predict left ventricular reverse remodeling (LVRR) in recent-onset dilated cardiomyopathy (DCM).

Methods:
A total of 29 patients with DCM underwent cine CMR and triple-slice T1 mapping using the MOLLI sequence at 3T, and EMB before receiving guideline-directed medical therapy. Poly ADP-ribose (PAR) nuclear and sirius-red staining were used for quantification of DNA damage and collagen volume fraction (CVF), respectively. LVRR was defined as an increase in LV ejection fraction of ≥10% to the final value of >35%, accompanied by a decrease in LV end-diastolic volume ≥10% at the follow-up CMR.

Results:
Fifteen patients (52%) achieved LVRR. The mean native T1, histological CVF, and proportion of PAR-positive nuclei were 1376 ± 55 ms, 0.13 ± 0.05, 25 ± 15%, respectively. Native T1 correlated well with CVF (p=0.004) and trended to be higher in DCM patients with increased DNA damage (p=0.17). There was no significant association between CVF and %PAR-positive nuclei. Native T1 <1400 ms provided 86% sensitivity and 67% specificity, with the C-statistic of 0.82 (95% CI 0.67-0.98) for predicting LVRR. By contrast, C-statistic of %PAR nuclei, CVF, and combined assessment of %PAR nuclei and CVF were 0.59, 0.61 and 0.66, respectively.

Conclusion:
CMR T1 mapping may be a promising strategy for noninvasive biopsy of the whole heart and provide a better prediction of LVRR in recent-onset DCM than comprehensive histological analysis of EMB.
Abstract 12680: Alcohol Consumption and Arrhythmia Recurrence After Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis
Authors: Grindal Alexander W , Sparrow Robert , McIntyre William F , Conen David , Healey Jeff S , Wong Jorge
Published: June 2023

Introduction:
Whether alcohol consumption increases the risk of atrial fibrillation (AF) recurrence following catheter ablation for AF remains unclear. We aimed to systematically review the medical literature to assess the impact of alcohol consumption on the recurrence of AF following AF

Hypothesis:
Elevated levels of alcohol consumption are associated with increased rates of AF recurrence following AF ablation.

Methods:
A structured electronic database search (MEDLINE, EMBASE, CONTROL; inception - December 2021) of the scientific literature was performed for studies reporting rates of AF recurrence following catheter ablation stratified by patients’ level of alcohol consumption. Alcohol use was dichotomized into categories which represented moderate-heavy alcohol use or those that represented abstention or rare alcohol use. Study specific odds rations (ORs) were meta-analyzed using a random effects model. Risk of bias was evaluated using the ROBINS-I tool.

Results:
A total of nine observational studies were identified, which included 5436 patients undergoing catheter ablation. There was substantial variation in the categories used to stratify alcohol consumption. Compared to patients consuming little to no alcohol, patients consuming moderate to high amounts of alcohol had a greater odds of AF recurrence (OR 1.45 [95% CI: 1.06-1.99, p = 0.02]; I
2
= 79%). This relationship remained significant after exclusion of studies with < 100 participants (OR 1.40, 95% CI 1.03-1.90, p = 0.03) and when abstract-only publications were excluded (OR 1.84, 95% CI 1.21-2.80, p = 0.004). All included studies were found to be at serious risk of bias, mainly due to confounding. There was no evidence of publication bias.

Conclusions:
Increased alcohol consumption is associated with increased rates of AF recurrence following catheter ablation for AF. Reduction of alcohol consumption post ablation may reduce AF recurrence.
Abstract 12697: Pharmacological Inhibition of BAG3-HSP70 With the Proposed Breast Cancer Therapeutic JG-98: In-vivo Mice Study
Authors: Manohar Hasitha D , Ma Emily , Cao Quan , Papadaki Maria , Osipo Clodia , Kirk Jonathan A
Published: June 2023

Introduction:
The co-chaperone Bcl2-associated athanogene-3 (BAG3), along with its cofactor heat shock protein 70 (HSP70), is fundamental for protein quality control and cell survival in a healthy heart. However, elevated expression of BAG3 is also associated with metastasis in breast and other cancers, and small molecules such as JG-98 that disrupt BAG3-HSP70 binding have been shown to reduce cancer cell proliferation. We previously showed JG-98 is cardiotoxic in neonatal rat ventricular myocytes.

Hypothesis:
As BAG3-HSP70 is fundamental for autophagic protein turnover, JG-98 will reduce tumor size but have cardiotoxic effects.

Methods:
BT474 Resistant breast cancer cells were injected bilaterally into mammary fat pads of female athymic nude mice. When tumors reached 25 mm
2
, mice received a baseline echocardiography and were randomized to intraperitoneal injections of either PBS/DMSO vehicle or 3 mg/kg JG-98 twice weekly for 3 weeks (n = 4/group) or 6 weeks (n=10/group). Tumor growth was monitored using calipers and echocardiography was performed prior to sacrifice.

Results:
After 3 weeks, tumor volume increased by ~44% in Vehicle treated mice but decreased by 17% in JG-98 treated mice, effectively halting tumor growth. However, cardiac echocardiography did not reveal any functional or structural differences between the vehicle and JG-98 treated mice after either 3 or 6 weeks. JG-98 did result in dysregulation of BAG3 and its interactome in the LV. JG-98 slightly increased BAG3 levels in the LV at 3 weeks, but slightly decreased levels at 6 weeks. This agrees with data showing acute stress upregulates BAG3, but chronic stress downregulates it. Similarly, we found altered protein expression of the BAG3 binding partners HSBP8, HSPB5, and HSP70.

Conclusions:
JG-98 had no overt cardiotoxic effects, suggesting the adult heart may be resistant to disrupted BAG3-HSP70. However, we also observed dysregulated protein levels in the BAG3-mediated autophagy pathways that could precede dysfunction with more chronic treatment. Furthermore, mutations in BAG3 or altered expression levels could sensitize individuals to JG-98 treatment. Further work is necessary to understand the cardiac impact of cancer therapeutics that target BAG3.
Abstract 12698: Alert-Driven versus Scheduled Remote Monitoring of Implantable Cardiac Defibrillators: An Economic Analysis From the Trust Randomized Trial
Authors: Chew Derek S , Piccini Jonathan P , Au FLora , Frazier-Mills Camille , Michalski Justin , Varma Niraj
Published: June 2023

Introduction:
Current implementation of remote patient monitoring (RPM) for implantable cardioverter defibrillators (ICDs) involves a hybrid of remote assessment and in-person evaluation (IPE) every 3 months. Alert-driven RPM or fully virtual care without routine visits may reduce non-actionable patient evaluation, increased clinic workload and inefficient resource allocation.

Objective:
To conduct a cost-consequence analysis to compare three patient management strategies following ICD implantation: (a) IPE only, (b) RPM-conventional (hybrid of IPE and RPM), and (c) RPM-alert (alert-based ICD follow up).

Methods:
We constructed a decision-analytic Markov model to estimate the costs and benefits of three strategies of patient management following ICD implantation over a two-year time horizon from the perspective of the US healthcare system. Aggregate and patient-level data from the TRUST (Lumos-T Safely RedUceS RouTine Office Device Follow-up) clinical trial informed clinical effectiveness model inputs. TRUST randomized 1339 patients 2:1 to conventional RPM or IPE alone, and found that RPM was safe and reduced the number of non-actionable encounters. Cost data was obtained from the published literature. The primary outcome was incremental cost.

Results:
The mean cumulative costs per patient were $12,688 in the IPE group, $12,001 in the RPM-conventional group, and $11,011 in the RPM-alert group. Compared to the IPE group, both the RPM-conventional and RPM-alert groups were associated with lower incremental costs of -$687 (95% confidence interval (CI)-$2,138 to +$638) and -$1,677 (95% CI -$3,134 to -$304), respectively. Of the three groups, the RPM-alert strategy was the most cost-effective strategy with an estimated cost-savings in 99% of simulations.

Conclusions:
Alert-driven RPM was economically attractive and, if patient outcomes and safety are comparable to conventional RPM, may be the preferred strategy of patient follow up.
Abstract 12706: Stroke Risk and Oral Anticoagulation Use With Extended Cardiac Monitoring for Atrial Fibrillation versus Usual Care: A Systematic Review With Meta-Analysis
Authors: Cheung Chris , MacDonald Blair , Turgeon Ricky , FIELD Thalia , Hill Michael D , Sposato Luciano , Ha Andrew , Verma Atul , Verma Subodh , Svendsen Jesper Hastrup , Larsen Jacob M , Diederichsen Søren , Tat Koh Keng , Andrade Jason G
Published: June 2023

INTRODUCTION:
Prolonged cardiac monitoring is frequently used to detect atrial fibrillation (AF) in high-risk populations, with the goal of preventing thromboembolic events. We sought to determine the impact of prolonged cardiac monitoring on the incidence of stroke and systemic embolism (SSE) or transient ischemic attack (TIA)

METHODS:
We performed a systematic review and meta-analysis of randomized trials evaluating prolonged monitoring versus usual care (PROSPERO #CRD42021277611). Studies were identified through CENTRAL, MEDLINE, and Embase. We included studies with ≥100 participants and ≥30 days follow-up. The primary outcome was a composite of SSE/TIA, as reported in the original trials. Secondary outcomes included AF detection, oral anticoagulation (OAC) initiation, and major bleeding. Sensitivity analysis examining the impact of monitoring device, and indication for monitoring were performed. Meta-analyses were performed with R using a random-effects model.

RESULTS:
From 1411 records, we included 9 RCTs (n = 10,205). Mean age was 70 years, 40% were female, and mean CHADS2 score was 4.0. Studies used implantable cardiac monitors (n = 4), external cardiac monitors (n = 3), or handheld ECG devices (n = 2). Study populations included post-stroke (n = 5), high risk for AF or stroke (n = 2), and post-cardiac surgery (n = 1). Mean follow-up was 16 months (range 3-65). Extended monitoring did not significantly reduce the primary outcome (Figure, random effects risk ratio [RR] 0.87, 95% confidence interval [CI] 0.72-1.06, I2 = 0%) or its individual components. Extended monitoring increased AF detection (RR 4.56, 95% CI 3.01-6.92, I2 = 65%) and OAC usage (RR 2.25, 95% CI 2.01-2.53, I2 = 0%), but did not impact major bleeding (RR 1.23, 95% CI 0.84-1.82, I2 = 0%).

CONCLUSION:
Prolonged monitoring was associated with increased AF detection and OAC use, without significantly reducing the occurrence of thromboembolic events.
Abstract 12707: The Association Between Beta-Blockers and Outcomes in Patients With Heart Failure and Alzheimer's Disease and Related Dementias
Authors: Gilstrap Lauren , Cohen Andrew , Ouellet Gregory , Goyal Parag , Gladders Barbara , Flint Danette , Skinner Jonathan
Published: June 2023

Introduction:
Contemporary HFrEF patients are older and have a higher prevalence of cognitive impairment compared to those studied in the original beta-blocker (BB) trials. While BB decrease mortality and morbidity in HFrEF, their use has been linked to higher fall risk and possibly acceleration of cognitive decline among older adults with Alzheimer’s Disease and Related Dementias (ADRD). The risk/benefit trade-off of beta blocker (BB) use in patients with HFrEF and dementia has not been examined.

Methods:
Using a 100% sample of patients enrolled in Medicare A, B and a 40% sample of D with ≥1 hospitalization for HFrEF between 2008 and 2018, we created a cohort of beneficiaries with HFrEF but no prior diagnosis of ADRD. We then subset to the population to those that developed ADRD in the year after their HFrEF hospitalization and compared BB use pre/post ADRD diagnosis and is association with outcomes using a time varying exposure.

Results:
The highest 1-year survival after ADRD diagnosis was observed among those continued on BB after ADRD diagnosis, regardless of whether they were on BB before (HR 0.427, 95% CI 0.406, 0.465, p<0.001) the ADRD diagnosis or not (HR=0.629, 95% CI 00.545, 0.670, p<0.001;
Figure 1
). The poorest survival was observed among those who had their BB stopped after their ADRD diagnosis (HR=2.34, 95% CI 2.15, 2.46).

Conclusion:
Among patients with HFrEF, stopping BB therapy after a diagnosis of ADRD is associated with the poorest survival. The best survival was observed among those continued on BB after ADRD diagnosis. Therefore, unless there is a clear clinical indication, BB therapy should not be stopped after a diagnosis of ADRD.
Abstract 12714: Impact of Reduced Left Ventricular Filling Pressure on Diastolic Function During Exercise in Patients With HFpEF
Authors: Abbas Syed A , Wakeham Denis J , Balmain Bryce , Tomlinson Andrew , Morris Margot , Moran Raksa , Payne Marcus , Samels Mitchel , Babb Tony , Levine Benjamin D , Sarma Satyam , Macnamara James P
Published: June 2023

Background:
During exercise, patients with heart failure with preserved ejection fraction (HFpEF) have an exaggerated increase in pulmonary capillary wedge pressure (PCWP) and left atrial-left ventricular pressure gradient (E wave velocity), as well as a blunted increase in early diastolic recoil (e’ velocity). It is unknown if non-invasive markers of diastolic function improve when exercise PCWP is acutely ameliorated.

Methods:
Patients with invasively proven HFpEF (n = 34, 71±6 years, 59% female, PCWP > 25 or Δ15 mm hg at peak exercise) underwent 2 seated cycle exercise tests with sublingual nitroglycerin (NTG) and placebo (PLB) in a cross-over design. PCWP (right heart catheter), tissue Doppler velocities of the mitral annulus (e’) and mitral inflow velocities (E) were measured at rest and during 20-watt submaximal steady state exercise. Differences between placebo and GTN conditions were assessed by repeated measures mixed model.

Results:
PCWP was 7.6±3.9 mmHg at rest and 21.1±7.8 mmHg with sub-maximal exercise and was decreased by 14% and 24% respectively by NTG (Drug effect p < 0.001,
Figure
). Mean E’ was 6.2±1.5 cm/sec at rest and 8.8±1.7 cm/sec during exercise and was decreased by 6% and 8% respectively by NTG (p = 0.003), but augmentation during exercise was unchanged (NTG +36%, PLB +41%, p = 0.211). The E wave velocity was 69.6±21.2 cm/sec rest and 101.9±31.3 cm/sec during exercise and was decreased by 12% and 11% with NTG respectively (p <0.001), but augmentation during exercise was unchanged (NTG +48%, PLB +46%, p = 0.507).

Conclusions:
NTG significantly and acutely lowered exercise PCWP in patients with HFpEF but did not improve diastolic function as assessed by echocardiography. The symmetrical slowing of E wave velocity and e’ with reduced PCWP demonstrate that higher preload helps maintain diastolic recoil and early diastolic filling for patients with HFpEF. Therapies that reduce preload in HFpEF may result in apparently worsened markers of diastolic function.
Abstract 12722: The Impact of Covid-19 on Patients in Cardiac Rehabilitation Phase II
Authors: Crutcher Kimberly , Krebs Harrison , Su Yan A , Prasun Marilyn A
Published: June 2023

Introduction:
COVID-19 significantly affected outpatient cardiac rehabilitation which is a central resource for patients recovering from cardiovascular disease. The aim of the study was to examine the impact of COVID-19 on Cardiac Rehabilitation (CR) Phase II clinical outcomes.

Methods:
A single-site retrospective chart review of CR Phase II patients who completed 12 or more visits during 2019 (pre-COVID) and 2020 (COVID) was performed. Depression was measured using the PHQ-9, functional capacity was measured by the 6-minute walk in distance (ft) and metabolic equivalents (METs), and quality of life (QOL) was measured by the Ferrans and Powers Index. Descriptive and linear mixed methods were used to analyze the data.

Results:
A total of 212 patients who were predominately male 67% and 66.5 (SD=10.8) years old were included. PHQ-9 results showed a significant interaction COVID*pre-post scores F(1, 119.66) = 4.66, p =  0.03. For the remaining scores, all results showed significant improvements in pre-post: distance F(1, 151.90) = 226.92, p <.001; METs F(1, 180.13) = 138.7, p <.001; and QOL F(1, 145.32) = 5.89, p =0.02. Interactions were not significant for the three variables. QOL results showed significant differences in the COVID group with F(1, 239.12) = 6.13, p =  0.01.

Conclusions:
All four outcomes improved significantly in the pre-COVID and COVID sample. COVID significantly impacted depression PHQ-9 score change, with a pre-post improvement of 0.62 points in the pre-COVID group and 2.08 points during COVID. Finally, the mean overall QOL score was significantly lower in the COVID group than the pre-COVID group.
Abstract 12725: Sarcopenia With Low Serum Albumin is Associated With Worse Prognosis in Patients Hospitalized for Acute Decompensated Heart Failure
Authors: Mirzai Saeid , Persits Ian , Sarnaik Kunaal , Estep Jerry , Chen Po-Hao , Tang Wai Hong W
Published: June 2023

Introduction:
Low serum albumin is a marker of protein malnutrition and is commonly associated with worse outcomes in various clinical settings. Furthermore, significant overlap exists between malnutrition and sarcopenia, which can be an independent predictor of worse outcomes.

Hypothesis:
We assessed the hypothesis that the presence of sarcopenia with low albumin (SLA) would lead to synergistically worse outcomes in patients with acute decompensated heart failure (ADHF).

Methods:
Patients hospitalized for ADHF from 2017 to 2019 with computed tomography of the abdomen/pelvis within 30 days and albumin level within 24 hours before discharge were studied (n=181). Given the high prevalence of hypoalbuminemia, low albumin was defined as the lower fiftieth percentile. Semi-automatic measurements of skeletal muscle area were made at L3 (Figure 1A) and adjusted using height squared to obtain skeletal muscle index (SMI). Sarcopenia was defined as the lowest sex-stratified SMI tertile.

Results:
The prevalence of sarcopenia alone was 11.6%, low albumin alone 28.7%, and SLA 20.4%. The groups had similar demographics but differed in BMI (lowest in sarcopenia alone, p<0.001) and admission NT-proBNP (highest in SLA, p=0.029). Patients with SLA were discharged to facilities most often (55.2%, p<0.001). All-cause mortality differed among the groups (p<0.001) during a median follow-up of 23.4 (4.2-45.0) months (Figure 1B). Compared to controls, those with SLA were at the highest risk (HR 2.46, 95%CI 1.50-4.02, p<0.001), followed by patients with low albumin alone (HR 1.77, 95%CI 1.11-2.83, p=0.016) or sarcopenia alone (HR 1.73, 95%CI 0.93-3.20, p=0.082), the latter not reaching significance.

Conclusions:
In conclusion, sarcopenia with low serum albumin is associated with higher mortality. Available resources and interventions should be utilized during ADHF hospitalization to optimize nutrition for these patients.
Abstract 12733: Understanding the Care Priorities of Older Patients With Heart Failure
Authors: D'Anna Susan , Emmons Margaret , Cantlin Deborah , DeMark Carolyn , Mujtaba Mohammadtokir , Gilstrap Lauren
Published: June 2023

Introduction:
The average age of a Medicare beneficiary with heart failure (HF) is now 80 years old. As patients age, their care priorities may change. At present, “high quality” HF care is determined by the use of appropriate medications to forestall or reverse disease progression. The aim of this study to identify other care priorities among older adults with HF that should be considered when measuring the quality of HF care.

Methods:
We conducted semi-structured interviews with 41 patients ≥75 years old with HF. The oldest was 93 years old and the youngest was 75 with an average age of 82. Interviews were conducted in both the inpatient (n=23) and outpatient/clinic (n=18) settings. Patients were asked a series of 10 questions focused on care priorities and the characteristics of “high quality” care. Interviews were recorded and transcribed. The longest interview was 19:59 minutes, the shortest was 4:20 minutes and the average was 10:32 minutes. Recordings were listened to while reviewing the transcripts, then analyzed and coded for thematic analysis.

Results:
The domains of high quality care highlighted by older patients are described in
Figure 1.
The most important aspects of HF care included: “getting the right medicine” and “making me comfortable as long as I can be.” Patients defined high quality care as: “a team that listens” and “follows up.” A high quality provider was distinguished from a low quality provider by “honesty,” “compassion” and “the ability to listen.” When asked how providers/teams should be evaluated, patients recommended metrics that captured: “knowledge,” “communication” and “really caring.”

Discussion:
Current HF quality metrics capture less than half of the care domains that are important to older patients with HF. Additional work is needed to create novel quality metrics to incentivize all domains of high quality HF care.
Abstract 12735: Autoimmune Recurrent Pericarditis in Pregnancy: A Multidisciplinary Approach
Authors: Mazumder Samia , Karmali Rehan , Sankar Parvathy Ravi , Berglund Felix , Majid Muhammad , Klein Allan L
Published: June 2023

Background:
Recurrent pericarditis in pregnancy is uncommon and the data regarding the safety and efficacy of conventional therapy is sparse. We describe a multidisciplinary approach to managing a challenging case of chronic, recurrent pericarditis in the setting of newly-diagnosed systemic lupus erythematosus (SLE) and pregnancy.

Case:
28-year-old female at 24 weeks gestation with no known medical history presents with sharp, pleuritic and positional chest pain and hypotension. Transthoracic echocardiography reveals acute, effusive pericarditis with features of tamponade. Despite emergent pericardiocentesis, pericardial window placement and treatment with steroids, she had recurrence of pericarditis the following month. Due to the recurrent nature of pericarditis of unknown etiology and pregnancy, clinicians were faced with a diagnostic and therapeutic dilemma.

Decision Making:
After extensive testing to rule out malignancy, bacterial and fungal infections, she was diagnosed with SLE - the culprit of her recurrent pericarditis. An multidisciplinary approach among cardiology, rheumatology and obstetrics was taken to determine an optimal therapeutic regimen and several risk-benefit discussions were conducted with the patient and family. In order to treat both recurrent pericarditis and SLE, she was tapered off of steroids initiated on Azathioprine 50 mg and low-dose Colchicine 0.3 mg twice daily. She was followed closely with cardiac MRI (Figure 1) and ultimately delivered a healthy child despite her new diagnoses.

Conclusion:
This case showcases the complexity of managing recurrent pericarditis in the setting of pregnancy and comorbid conditions and supports the use of Colchicine and Azathioprine for this population despite the lacking literature. This case also emphases the importance of multidisciplinary teamwork, clinical acumen and the value of patient-centered care when determining a course of therapy for a challenging patient.
Abstract 12740: Racial and Ethnic Disparities in Mortality in Patients Presenting With STEMI With COVID-19: NACMI Registry
Authors: Quesada Odayme , Yildiz Mehmet , Walser-Kuntz Evan , Stanberry Larissa I , Garberich Ross , Bagur Rodrigo , ghasemzadeh nima , Keshav Nayak , Bagai Akshay , wiley jose , SINGH Avneet , Aragon Joseph , Amlani Shoaib , Cox Pedro , Dai Xuming , Alyousef Tareq , Kabour Ameer , Patel Rajan D , Garcia Santiago A , Alraies M C , Dehghani Payam , Henry Timothy D
Published: June 2023

Introduction:
COVID-19 infection disproportionally impacts non-Whites with higher morbidity and mortality. However, differences by race and ethnicity in COVID-19 patients with concomitant STEMI have not been previously described.

Methods:
The North American COVID-19 STEMI (NACMI) registry is a prospective, observational registry enrolling COVID-19 patients with concomitant STEMI from 64 centers in Canada and the United States from March 2020 to December 2021. We compared clinical characteristics, treatment strategies, and in-hospital mortality risks by race/ethnicity.

Results:
Among 679 STEMI patients with concomitant COVID-19, 54.5% were White, 14.3% Black, 19.4% Hispanic/Latinx, and 11.8% Asian/Indigenous/Other. Blacks had the highest prevalence of current smokers, and Whites had the lowest prevalence of diabetes. The rate of high-risk features including cardiac arrest, cardiogenic shock, and inotropic support was comparable between the groups. Presence of infiltrates and cardiomegaly was higher in Blacks and Hispanic/Latinx; whereas, COVID-19 severity was similar in the groups. Blacks and Hispanic/Latinx and Blacks were more likely to not have coronary angiography performed. Among patients that underwent angiography, Whites and Hispanic/Latinx were more likely to be treated with primary PCI. In-hospital mortality was highest in Hispanic/Latinx (38%) and the Asian/Indigenous/Other group
(Table).

Conclusions:
Despite no difference in high-risk features in patients with COVID-19 and STEMI, there was a significant difference in in-hospital mortality between Whites and non-Whites with highest risk in Hispanic/Latinx and Asian/Indigenous/Other. Further research in needed to explore discrepant outcomes in racial/ethnic minorities in this patient population and the role of discrepant management.
Abstract 12758: Maternal Gestational Diabetes is Associated With Increased Aortic Stiffness in Pre-Adolescent Children
Authors: Boehme Cleighton , Moran Martha , Do Victor , Lasso-Mendez Juliana , Bell Rhonda C , Fruitman Deborah S , Cooke Christy-Lynn , Hornberger Lisa K
Published: June 2023

Introduction:
Population studies have suggested adults born to mothers with gestational diabetes mellitus (GDM) have increased risk of cardiovascular (CV) disease. Whether GDM exposure before birth is associated with abnormal CV health in childhood is unknown. In the present study, we prospectively explored the CV health of children of mothers with GDM (CGDM) with comparison to children of healthy mothers (controls) and examined relationships with maternal variables.

Methods:
CGDM and age- and sex-matched controls were recruited from the longitudinal Alberta Pregnancy Outcomes and Nutrition Birth Cohort Study and underwent CV assessments. Outcome measures included left ventricular mass Z-score, EndoPAT reactive hyperemia index score (endothelial function), Doppler-based aortic and peripheral (common carotid to posterior tibial artery) pulse wave velocity (PWV), and carotid intima-media thickness. CGDM were further stratified into groups according to how maternal GDM was controlled (diet vs insulin). The mother’s pre-pregnancy body mass index (BMI), adherence to the 2007 Canada’s Food Guide, and intake of less healthy foods in the 2
nd
and 3
rd
trimesters of pregnancy were also examined.

Results:
We assessed 25 CGDM and 27 controls (mean age 10.9±0.7 years) with comparable birth and baseline characteristics (Table). Aortic PWV was higher in CGDM vs controls (p=0.03), and higher in CGDM of insulin vs diet controlled mothers (p=0.03). No other measures of CV health differed. Mothers with GDM, but not controls, showed evidence of dietary improvement from the 2
nd
to 3
rd
trimester with improved adherence and reduced less healthy foods. Maternal BMI was unrelated to the child’s CV health.

Conclusions:
Even with maternal dietary improvement, CGDM have increased aortic stiffness, highest in offspring of mothers managed with insulin. Further work is needed to investigate the mechanisms by which GDM impacts the child’s vascular health and long-term implications.
Abstract 12767: Sodium-Glucose Cotransporter-2 Inhibitors Are Associated With Lower Risks of Hospitalization for Heart Failure and All-Cause Mortality in Patients With Diabetes Mellitus and Cancer
Authors: Chiang Cho Han , CHIANG CHO HUNG , Chiang Cho Hsien , Ma Kevin , Peng Chun-Yu , yuanping HSIA , Horng Chuan-Sheng , CHEN CHENG-YING , Chang Yu-Cheng , See Xin Ya , Chen Yuan-Jen , Wang Shih-Syuan , Suero Abreu Giselle A , Peterson Linda R , Thavendiranathan Paaladinesh , Armand Philippe , Peng Cheng-Ming , Shiah Her-Shyong , Neilan Tomas G
Published: June 2023

Introduction:
Patients with cancer face a heightened risk of cardiovascular (CV) events and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce CV events in at-risk patients and may possess antitumor effects. Therefore, we examined the effect of SGLT2i on CV events and mortality among patients with cancer and diabetes.

Methods:
This was a retrospective propensity score-matched cohort study conducted at two tertiary referral centers in Taiwan. We included all adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalization for incident heart failure (HF) and all-cause mortality. The secondary outcomes were a composite of myocardial infarction, ischemic stroke, and cardiac arrhythmias, and serious adverse events associated with SGLT2i.

Results:
From a total of 8640 patients, 878 SGLT2i-recipients were matched to non-recipients. During a median follow-up period of 18.8 months, SGLT2i recipients had a lower rate of hospitalization for incident HF compared with non-SGLT2i recipients (2.92 vs. 8.95 per 1000 patient-years, p=0.018). In both Cox regression and competing regression models, SGLT2i were associated with a 70% reduction in the risk for hospitalization for incident HF (HR, 0.28 [95% CI: 0.11-0.77], p = 0.013; SHR, 0.32 [95% CI: 0.12-0.84], p = 0.021). The use of SGLT2i was associated with a higher overall survival (85.3% vs. 63.0% at 2 years, p<0.001). The risk of myocardial infarction, ischemic stroke, cardiac arrhythmias, and serious adverse events such as hypoglycemia, urosepsis, and sepsis was similar between the SGLT2i and non-SGLT2i cohorts.

Conclusions:
The use of SGLT2i was associated with a lower rate of hospitalization for incident HF and prolonged overall survival in cancer patients with diabetes mellitus.
Abstract 12786: Contemporary Outpatient Management of Patients With and Without Worsening Heart Failure With Reduced Ejection Fraction Within A Single Integrated System: Results From Electronic Medical Record Data in the CHART-HF Study
Authors: Gaggin Hanna K , Greene Stephen J , Zhou Mo , Lautsch Dominik , Song Yan , Signorovitch James , Stevenson Andra S , Blaustein Robert , Butler Javed
Published: June 2023

Background:
Patients with HFrEF and worsening HF events (WHFE) have substantial disease burden and poor outcomes. CHART-HF aims to characterize real-world clinical characteristics, longitudinal treatment use, and therapeutic decision-making among patients with HFrEF with vs without WHFE.

Methods:
Retrospective analysis of EMR data of 1000 adult patients with HF (with LVEF <45%) from a single integrated health system with 2 mutually exclusive cohorts was conducted. The WHFE cohort included patients with a WHFE (i.e., hospitalization or receipt of IV diuretics) between 2017-2019 followed by an index outpatient cardiology visit ≤6 months. The control cohort included patients with no WHFE in a given year between 2017-2019. Index visit was defined as the last outpatient cardiology visit in the given year. Treatment use followed for 12 months.

Results:
Patients with WHFE were slightly older (68.6 vs. 68.0 years), had more females (28.8 vs. 24.4%) and had more comorbidities such as hypertension, atrial fibrillation, COPD, diabetes mellitus and chronic kidney disease compared with control patients (p>0.05). On index date, 81% of WHFE cohort patients were on beta blocker (BB), 55% on ACEI/ARB/ARNI, and 18% on MRA (
Figure, Panel A
) while 75%, 66%, and 22%, respectively, in the control cohort (
Figure, Panel B
). In both the WHFE and control cohorts, use of BB and ACEI/ARB/ARNI decreased while patients without any GDMT increased in the 12 months. The most frequent reason for not changing GDMT was “clinically stable and/or adequate symptom control” (
Figure, Panel C
). The median time to next HF hospitalization or death was 30 and 136 weeks from index date in WHFE and control cohort, respectively (p<0.001).

Conclusion:
Among US patients with HFrEF, there remain major gaps in use of GDMT and these gaps persist during longitudinal outpatient follow-up. These longitudinal gaps in GDMT are particularly large among the high-risk subset of patients with a recent WHFE.
Abstract 12799: Improving Healthcare Quality Through Innovative Training in Implementation Science
Authors: Farr Stacy L , Olds Danielle , Spertus John A , Sales Anne
Published: June 2023

Introduction:
Despite the rapid accumulation of evidence, translating this evidence into clinical practice is slow and inefficient. A key barrier is limited understanding of implementation science (IS). As part of a regional strategy to improve the value of healthcare, the Healthcare Institute for Innovations in Quality (HI-IQ) built a curriculum and certificate program, Training in Implementation: Actionable Research Approaches (TIARA) to train researchers and providers with skills in IS.

Methods:
HI-IQ has built a multi-stakeholder consortium, conducted a healthcare needs assessment, and begun regional QI implementation across multiple hospitals. To support regional QI, TIARA 1.0 was developed and launched as a Certificate program from the Frontiers Clinical & Translational Science Institute (CTSI), with online recordings (www.kcqvic.org/trainings/).

Results:
Participants (n=120) in TIARA 1.0 came from hospitals, payers, health departments, community-based organizations, and academic institutions. Over 60% of participants reported increases in IS expertise after training. Across all IS competencies (n=8), participants increased an average of 3.7 points (Figure 1). These skills are being applied in a regional program to improving transitions in care for heart failure to not only evaluate the outcomes, but also the facilitators and barriers to implementing the evidence. Due to demand for more and expanded training opportunities in IS, both coursework and additional professional training are being developed.

Conclusions
: There is a significant unmet need to expand skills in IS for those working in real-world quality improvement and clinical care. HI-IQ’s training approach, utilizing online-hybrid delivery, applied content for practitioners, and real-world project-based applications are promising strategies to train practitioners in how to change healthcare and can model a strategy for other regions to consider in improving care.
Abstract 12814: Atrial Fibrillation Risk Prediction Through Integration of Imaging-Based Biomarker: The Multi-Ethnic Study of Atherosclerosis
Authors: Manubolu Venkat S , Varadarajan Vinithra , Aldana-Bitar Jairo , Verghese Dhiran , Alalawi Luay , Kinninger April , Roy Sion , Ac Lima Joao A , Heckbert Susan R , Budoff Matthew
Published: June 2023

Introduction:
Despite the best risk prediction tools, there seems to be a significant amount of residual risk of atrial fibrillation (AF) that justifies new risk prediction strategies. The CHARGE- AF simple model outperforms other existing models. This study aims to evaluate the predictive ability of cardiac MRI-based imaging biomarkers in addition to the CHARGE AF simple model.

Methods:
MESA is an observational cohort study of 6,814 men and women from six U.S. communities between the ages of 45 and 84 years, who were initially free of clinical CVD. We included 4185 participants after excluding baseline AF (n=70) and missing values of imaging biomarkers (n=2559) at the baseline exam. Left atrial (LA) volume and left ventricular (LV) volumes were obtained from cardiac MRI measurements. Multivariable Cox regression was used to assess the independent 5/10-year AF predictive ability of imaging biomarkers in addition to the baseline model while adjusting for confounders.

Results:
4,185 participants were included in the study. The average age (SD) was 61(±10) years, 47% male, 13% current smokers, and 39% White with a median follow-up of 17 years. Of this population, 19% developed AF. In multivariable regression models, a 1 ml increase in LA volume was significantly associated with a 3 to 10% higher risk of developing AF. Compared to the baseline model (M1, with no imaging biomarker), the 5 /10-year risk prediction of atrial fibrillation was improved after adding the imaging biomarkers for models 2, 3, and 6 (Table 1). The 5 /10 years concordance index for assessing risk prediction increased marginally from 80 / 79% in M1 to 84 / 81%, 84 / 81%, and 84 / 81% in M2, M3 and M6 respectively (all p values < 0.0001).

Conclusions:
The incorporation of MRI-based LA volume index into the CHARGE AF simple model demonstrated a modest improvement in the 5/10-year risk prediction of AF. The clinical benefit should be interpreted with caution due to marginal improvement in risk prediction.