bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12100: Exploration of Proteomic Risk Markers for Incident Heart Failure and Cardiac Remodeling in Three European Population-Based Cohorts
Authors: Dieden Anna , Jujic Amra , Ottosson Filip , Molvin John , Pareek Manan , MELANDER Olle , Råstam Lennart , Lindblad Ulf , Daka Bledar , Leosdottir Margret , Holmes Hannes , Nilsson Peter , Hecht Olsen Michael , Duarte Kevin , ZANNAD Faiez , Girerd Nicolas , Magnusson Martin
Published: April 2022

Introduction:
Several biomarkers have been linked with incident heart failure (HF), but the pathophysiology of HF is complex and multifactorial.

Hypothesis:
We explored 92 biomarkers’ associations with left ventricular hypertrophy (LVH), prevalent LV diastolic dysfunction (LVDD), and incident HF in three European population-based cohorts.

Methods:
Profiling of 92 biomarkers was carried out in 1737 participants from the echocardiography subsample of the population-based cohort study, the Malmö Preventive Project (mean age 67 years, 29% women). The final study sample consisted of 1681 subjects for analyses of incident HF (n=130), and 1530 subjects for analyses of LVDD (n=109) and LVH (n=498). Multivariable Cox regression analyses excluding subjects with prevalent HF were carried out for incident HF. Multivariable logistic regression analyses excluding subjects with reduced or mid-range LV ejection fraction (<50%) were carried out for LVDD and LVH. Replication analyses of significant findings were carried out in the HOMAGE (562 cases of incident HF, 871 controls) and STANISLAS cohorts (304 cases of LVDD and 1668 controls; and 245 cases of LVH and 1681 controls).

Results:
In the multivariable model adjusted for clinical risk factors, six proteins were associated with incident HF (median follow-up time 12.6, interquartile range 10.9-13.6 years): ST2 (hazard ratio (HR) 1.40; 95% confidence interval (1.03-1.91); p=0.031), GDF-15 (HR 1.33 (1.00-1.77); p=0.048), AZU1 (HR 1.42 (1.10-1.82); p=0.006), MPO (HR 1.48 (1.02-2.15); p=0.041), Gal-4 (HR 1.37 (1.02-1.85); p=0.038) and NT-proBNP (HR 1.98 (1.66-2.36); p=2.1x10
-14
) in the discovery cohort. In the replication cohort, ST2, GDF15, NT-proBNP and Gal-4 also displayed significant associations with incident HF. In analyses of DD, none of the associated proteins in the discovery cohort (AZU1; TR; PCSK9 and NT-proBNP) were replicated in the STANISLAS cohort. Among AZU1, PGLYRP1, and NT-proBNP, NT-proBNP was the only protein that was significantly associated with LVH in both cohorts.

Conclusions:
We replicated the association of ST2, GDF-15, NT-proBNP and Gal-4 with incident HF, whereas NT-proBNP was the only biomarker that was associated with LVH as well as incident HF in discovery and replication cohorts.
Abstract 12113: Deletion of Extracellular Signal-Regulated Kinases 2 Using SM22α-Cre Driver Causes Cardiac Failure and Vascular Dysfunction
Authors: Kagami Kazuki , Yumita Yusuke , Iwashita Midori , Yuki Ishinoda , Namba Takayuki , Toya Takumi , Ikegami Yukinori , Yasuda Risako , Masaki Nobuyuki , Ido Yasuo , Nagatomo Yuji , Adachi Takeshi
Published: April 2022

Background:
Extracellular signal-regulated kinases 1/2 (ERK1/2) play significant roles in proliferation, migration, and cell death. Tyrosine kinase inhibitors (TKIs) have a serious concern for cardiotoxicity and these agents target to EGFR/Ras/Raf/MEK/ERK pathway. In previous reports, SM22α-Cre drived EGFR receptor knockout mice revealed cardiac dysfunction.

Hypothesis:
We hypothesized if SM22α-Cre drived ERK2 contributed to the cardiac dysfunction mimicking toxicity of TKIs.

Methods & Results:
We generated SM22α-drived ERK2 knockout mice (SM22α-EKO) by crossing SM22α-Cre mice and ERK2-flox mice. The protein expressions of ERK2 in aorta and heart were markedly lowered in SM22α-EKO, whereas similar in brain, kidney, liver, spleen, and bone marrow. SM22α-EKO displayed lower exercise tolerance and peak oxygen consumptions. Echocardiography revealed left ventricular thickness and dilatation with decreased % fraction shortening (21±4 vs. 38±2%, p=0.0002). Pathological study showed that heart weight was twice accompanied by increases in cardiomyocyte volume, stronger cardiac fibrosis, and inflammations (Figure 1). Western blot analysis showed that the phosphorylation of Akt, p-38 MAP kinase, and STAT3 were also up-regulated in SM22α-EKO with control. Phenylephrine - induced vascular contraction was increased and acetylcholine - induced relaxation was impaired in SM22α-EKO. Finally, SM22α-EKO significantly reduced life span in the Kaplan-Meier plot (Figure 2).

Conclusion:
SM22α-EKO mice revealed spontaneous cardiac dysfunction with the activation of multiple signaling cascades for hypertrophy and inflammation resulting in sudden death. Deletion of ERK2 in heart and smooth muscle cells also led to hypercontraction of phenylephrine / endothelial dysfunction and perivascular cardiac fibrosis and inflammation. SM22α-EKO might be a valuable model for TKI - induced cardiotoxicity.
Abstract 12120: Cost-Effectiveness of Earlier Initiation of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With a History of Heart Failure
Authors: Miller Robert , Chew Derek , Qin Lei , Fine Nowell , McMurray John JV , Howlett Jonathan G , McEwan Phil
Published: April 2022

Background:
Patients with heart failure (HF) are at increased risk after hospitalisations for HF (HHF). Timely initiation of medical therapy may reduce morbidity and mortality in these patients. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial demonstrated that dapagliflozin reduced the risk of worsening HF and mortality when added to guideline-directed medical therapy (GDMT). Whilst previous economic evaluations have demonstrated that dapagliflozin is cost-effective; timing of initiation has not been considered.

Objective:
This study assessed whether early addition of dapagliflozin (D+GDMT) was cost-effective compared to a 12-month delay.

Methods:
A published lifetime Markov model was utilised with health states defined by Kansas City Cardiomyopathy (KCCQ) score, type 2 diabetes status and incidence of HF events. We analysed the DAPA-HF trial to estimate the incidence of HF events using a negative binomial regression model, and parametric survival analysis for all-cause death. Direct healthcare costs (2019 GBP) and utility values were sourced from the published literature and DAPA-HF, respectively. We estimated lifetime costs and quality adjusted life years (QALYs) for early initiation of D+GDMT compared to a 12-month delay.

Results:
Standard therapy was associated with lifetime costs of £12,641 and 4.11 QALYs. Treatment with D+GDMT with 12 months delay was associated with total discounted lifetime costs and QALYs of £15,966 and 4.71 respectively. Early initiation was associated with lifetime cost and QALYS; £16,518 and 4.78 respectively. Consequently, early initiation was associated with an additional cost of £552 and QALY gains of 0.08 resulting in an incremental cost effectiveness ratio of £8,515.

Conclusion:
Early or late initiation of D+GDMT is cost-effective. However, earlier initiation is associated with rapid improvement in patient symptoms leading to 10% greater QALY gains at a very attractive ICER.
Abstract 12121: Coronary Disease Association With ADAMTS7 is Due to Protease Activity: Implications for Therapeutic Development
Authors: Mizoguchi Taiji , MacDonald Bryan T , Bhandary Bidur , Popp Nicholas R , Laprise Dylan , Arduini Alessandro , Lai Daniel , Zhu Qiuyu M , Xing Yi , Kaushik Virendar K , Kathiresan Sekar , Ellinor Patrick T
Published: April 2022

Background:
Despite contemporary therapy, coronary artery disease (CAD) remains a leading cause of mortality. Genetic variants at ADAMTS7 have been associated with CAD and the loss of ADAMTS7 is protective for atherosclerosis. ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs 7) is a secreted metalloproteinase and complex proteoglycan, yet the mechanism linking ADAMTS7 to CAD risk remains unresolved.

Methods and Results:
We established a new purification strategy for full-length mouse ADAMTS7 and demonstrated the loss of activity in the catalytic mutant form of ADAMTS7. To test if the enzymatic activity of ADAMTS7 mediates atherosclerosis, we generated a catalytically inactive mutant mouse allele and compared it to the
Adamts7
knockout. Using two models of atherosclerosis, we found that reducing either ADAMTS7 dosage or catalytic function decreased the burden of atherosclerosis. We demonstrate impaired vascular smooth muscle migration in both
Adamts7
catalytic mutant and null cells using a lateral migration wound healing assay. Expression of the WT allele rescued the migration phenotype in
Adamts7
null cells while expression of the catalytic mutant protein did not. We then characterized a human
ADAMTS7
coding variant rs3825807 (Ser214Pro) associated with reduced CAD risk. This variant had a hypomorphic effect on ADAMTS7 secretion and migration of vascular smooth muscle cells, findings consistent with our mouse studies.

Conclusions:
We demonstrated that loss of ADAMTS7 catalytic function protects against atherosclerosis via phenotype switch of VSMCs and that the atherosclerosis protective effects could be mediated by a loss-of-function coding variant associated with CAD risk. In aggregate, we provide compelling evidence that dosage of ADAMTS7 and catalytic function are responsible for the atherosclerotic phenotype, suggesting that the catalytic domain would be an attractive therapeutic target for CAD.
Abstract 12131: Improved Knowledge and Confidence of Antiarrhythmic Drugs in Atrial Fibrillation via Online Educational Intervention
Authors: Harris Margaret , Amara Walid , Chang Lih-Fan , Lacouture Michael , Guedj Philippe
Published: April 2022

Background:
Antiarrhythmic drugs (AAD) are currently used for the management of patients with arrhythmias. Despite randomized trial and real-world data many physicians remain hesitant to select an AAD in the daily-life routine.

Purpose:
To determine if an online continuing professional development intervention could improve knowledge and confidence of cardiologists and primary care physicians (PCPs) related to real-world data for AAD.

Methods:
Cardiologists and PCPs electively participated in a video-based, 2-faculty educational panel discussion on AAD management of arrhythmias, including real-world data. Educational effect was assessed using a repeated pair, pre-assessment/post-assessment study design and a chi-square test assessed differences from pre- to post-assessment.
P
-values < .05 are statistically significant. Cramer’s V assessed level of educational effect using the range of < 0.06 (modest), 0.06-0.15 (noticeable), 0.16-0.26 (considerable), and > 0.26 (extensive). Data were collected June 5, 2020 through July 20, 2020.

Results:
Overall significant improvements were seen after education for cardiologists (N = 367;
P
< .0001; V = .359) and PCPs (N = 760;
P
< .0001; V = .359). Pre-assessment, the average correct response rate was 32% for cardiologists and 29% for PCPs, while post-assessment average correct response rates increased to 68% and 61%, respectively. Significant improvements were observed in cardiologists’ and PCPs’ knowledge related to the effect of AAD on outcomes (Table). As a result of the education, 36% of cardiologists and 45% of PCPs had a measurable improvement in confidence regarding selection of appropriate antiarrhythmic therapy for patients with AF.

Conclusion:
The statistically significant improvements observed in this intervention demonstrate that participation in a video-based panel discussion improved the knowledge and confidence regarding real-world data for AAD regarding their effects on outcomes.
Abstract 12133: Association Between Polyvascular Disease and Adverse Outcomes Among Patients Undergoing Coronary Artery Bypass Grafting in a Regional Registry
Authors: Ramkumar Niveditta , Westbrook Benjamin M , Hirashima Fuyuki , Malenka David J , Ross Cathy S , Iribarne Alexander , Young Michael , Henkin Stanislav ,   The Northern New England Cardiovascular Disease Study Group
Published: April 2022

Introduction:
Polyvascular disease is defined as the simultaneous presence of coronary artery disease (CAD) and peripheral artery disease (PAD) or cerebrovascular disease (CVD).

Hypothesis:
We hypothesized that polyvascular disease may be associated with worse short- and long-term outcomes in patients undergoing coronary artery bypass grafting (CABG).

Methods:
We performed a retrospective, multi-center analysis of patients undergoing isolated CABG from 2005-2018 among 7 medical centers in Northern New England. Patients were stratified by number of vascular beds affected: CAD only, CAD+PAD or CVD, and CAD+PAD+CVD. The primary outcomes of 30-day and long-term mortality were assessed using multivariable logistic and Cox regression, respectively.

Results:
Of 18,984 patients, 18% had either PAD or CVD, while 4.8% had PAD and CVD. Compared to those with CAD alone, patients with polyvascular disease were older, more likely to be female, and had a higher prevalence of comorbidities including diabetes, smoking, and renal failure (all p<0.001). The risk-adjusted odds of 30-day mortality was higher for patients with either CVD or PAD (OR=1.57, 95% CI: 1.2-2.07) and combination of CVD and PAD (OR=1.56, 95% CI: 1.00-2.42) versus CAD alone. Polyvascular disease patients had higher risk of long-term all-cause mortality compared to CAD only patients (Figure).

Conclusions:
Among patients undergoing CABG in Northern New England, those with polyvascular disease had a higher risk of short- and long-term adverse outcomes compared to CAD alone, with incremental increase in risk dependent on number of vascular beds affected. Aggressive secondary prevention measures, prior to and after CABG, should be routinely employed for these patients.
Abstract 12136: Detection of Sub-Clinical Left Ventricular Dysfunction in COVID-19 Patients
Authors: Khalid Muhammad , Thodeti Sathwika , Mikolich Brandon , Mikolich J Ronald
Published: April 2022

Introduction:
Abnormalities of left ventricular (LV) strain have been shown to occur prior to impairment of global left ventricular function, measured by global LV ejection fraction (EF). Although first described in patients receiving cardiotoxic chemotherapy, impairment of LV strain prior to a decrease in EF has also been shown in many other disease states which affect LV function. This study was designed to assess impairment of LV strain in post COVID-19 patients with normal EF using cardiac MRI MyoStrain Fast-SENC (strain encoded) pulse sequences.

Methods:
An institutional cardiac imaging database was queried for all patients with documented COVID-19 test positivity and a normal LVEF >= 55% who underwent measurement of global longitudinal strain (GLS), global circumferential strain (GCS), and regional longitudinal and circumferential strain using cardiac MRI Fast-SENC pulse sequences. Global and regional strain measurements were compared to a cohort of healthy volunteers who also underwent CMR Fast-SENC imaging. Abnormal myocardial strain was defined as a value >-17%.

Results:
Of 50 COVID-19 patients in the cardiac imaging database who underwent CMR Fast-SENC imaging, 40 had a normal LVEF, constituting the study cohort. Mean GLS and GCS for the study cohort were -16.40% and -15.45% and for healthy volunteers were -19.71% and -20.93% respectively; both comparisons were statistically significant with an unpaired t-test (p<0.01). Furthermore, the prevalence of abnormal LV strain in COVID-19 patients with normal LVEF was 77.78%.

Conclusions:
These data suggest that impairment of LV strain (longitudinal and circumferential) occurs in COVID-19 patients who have a normal LVEF. Whether a decrease in GLS and/or GCS precede a decrease in LVEF, is beyond the scope of this study. However, the ability to evaluate progression of LV strain abnormalities with CMR may help identify changes in LV function before the onset of a reduction in LVEF and development of heart failure. The ability to identify and quantify abnormal left ventricular GLS and GCS with cardiac MRI also opens the door to assess any benefit of therapy, including anti-inflammatory agents, anti-viral drugs and steroids.
Abstract 12138: Cell Senescence Associated H3K9me3 Decline Sensitizes Aortic Valve Cell for Osteogenic Response
Authors: Shuwen Su , Shunyi Li , Jingxin Zeng , Gaopeng Xian , Xi Yang , Kaiji Xie , Qiong Zhan , Dingli Xu , Zeng Qingchun
Published: April 2022

Introduction:
Cell senescence has been identified as an impact etiological factor in cardiovascular diseases, as well as calcific aortic valve disease (CAVD) . In our previous experiment results, We found that a large number of senescent aortic valve interstitial cells (AVIC) accumulated in the calcific aortic valve tissues, especially around the calcification sites. But the role and mechanism of cellular senescence in the development of calcified aortic stenosis have not been clarified. We
hypothesized
valvular interstitial cell senescence sensitize interstitial cell for osteogenic response through enhancing cell senescence associated epigenetic modification.

Methods and Results:
Representative immunofluorescence results of the clinical samples show that p16INK4A positive cells in the calcific aortic valve expressed more osteogenic associated factors, such as Runx2 and BMP2. And RAS system hyperactivation seemed to be an impact association with aortic valve calcification. Then we found Angiotensin II (1μM, 72h) chronic irritation induces valve interstitial cell senescence associated secretion phenotype (SASP) and activates osteogenic response through ERK1/2 and NF-κB pathway. ChIP-qPCR results demonstrated H3K9Me3 modifications on the promoters of Runx2, ACTA2(also known as α-SMA), IL-6, IL-8, MCP-1 were significantly decreased in angiotensin II pretreated AVIC. Blockage of angiotensin II and ABT-263 pretreatment inhibited valvular interstitial cell to convert into osteoblast-like phenotype induced by Angiotensin II, as well as attenuating senescence associated secretion phenotype factors yield. Blockage of angiotensin II receptor and p16
INK4A
knockdown contributed to recover H3K9me3 modification on the promoters of those gene in angiotensin II pretreated AVIC through attenuating angiotensin II-induced ubiquitination degradation of SUV39H1.

Conclusion:
p16
INK4A
mediated H3K9me3 decline sensitizes aortic valvular interstitial cell for osteogenic response, which impacts on aortic valve homeostasis and aortic valve calcification. Taken together, p16
INK4A
positive senescent cells would be the potential target on prevention and treatment of calcific aortic valve disease.
Abstract 12139: Substance P Replacement Reduces Cardiac Fibrosis in Monkeys With Type 2 Diabetes
Authors: Melendez Giselle C , Kavanagh Kylie , Lacy Jessica L , Block Masha , Gharraee Nazli , Widiapradja Alexander , Levick Scott P
Published: April 2022

Introduction:
Type 2 diabetes mellitus (T2DM)-associated cardiac fibrosis contributes to heart failure, especially in women. We have data showing that diabetic mice with cardiomyopathy, including cardiac fibrosis, exhibit low levels of the neuropeptide substance P (SP); and SP replacement reverses cardiac fibrosis, independent of body weight and blood glucose. To understand the potential translational significance of these findings, we sought to determine in a T2DM monkey model if replacement SP could reverse cardiac magnetic resonance (CMR) imaging and circulating markers of fibrosis, while also assessing safety of administration.

Methods:
Female T2DM African Green monkeys were randomized to receive SP (n=4, 0.5 mg/Kg/day S.Q. injection) or vehicle (n=3) for 10 weeks. We obtained CMR imaging and blood samples to assess left ventricular (LV) function and fibrosis by T1 map-derived extracellular volume (ECV) and circulating procollagen type I C-terminal propeptide (PICP). Hematological parameters for toxicities were also assessed. We performed a blinded paired analysis of all parameters.

Results:
Monkeys receiving replacement SP exhibited a decrease in ECV (Pre: 31.6 ± 5.53% vs. Post: 25.2 ± 3.3%, p=0.03), concomitant with decreased PICP levels (Pre: 5148.58 ± 1143.5 ng/mL vs. Post: 3851.1 ± 1377.5 ng/mL, p=0.01). Animals receiving vehicle showed no changes in ECV (p=0.32) or PICP (p=0.16). No changes in LV ejection fraction were observed (p=0.89). Complete blood counts, metabolic panel (ΔA1c, SP: -0.45 ± 0.59 % vs vehicle: -0.53 ± 0.61 %, p=0.43), lipids, liver and pancreatic enzymes, and inflammation markers were unchanged (p>0.05 for all).

Conclusion:
Replacement SP reversed cardiac fibrosis in a large preclinical model of T2DM, independent of glycemic control. No organ-related toxicity was associated with replacement SP. These results strongly support a potential application for replacement SP as an antifibrotic therapy for diabetic cardiac fibrosis.
Abstract 12147: Prognostic Impact of Cardiac MRI Derived Left Atrial Volumetric and Functional Parameters in Patients With Advanced Ischemic Cardiomyopathy
Authors: Anthony Chris , Obuchowski Nancy , Popovic Zoran B , Tang Wilson , Griffin Brian P , Flamm Scott D , Kwon Deborah H
Published: April 2022

Background:
Left atrial (LA) size has been shown to be predictive of adverse outcomes in patients with various cardiac conditions. However, the significance of left atrial function (LAF) is not clearly defined in patients with advanced ischemic cardiomyopathy (ICM). We assess the effect of cardiac magnetic resonance imaging (CMR) based LA ejection fraction (LAEF), LA volume index (LAVi) and total LA strain(Las) on outcomes in patients with ICM.

Methods:
Patients with ICM, who underwent cardiac magnetic resonance (CMR) between January 2002 and January 2017, were included in our study. Clinical characteristics and CMR parameters were collected and analyzed. Maximum and minimum left atrial volume (LAV) and LAEF were calculated using the biplane area-length method. Multi-variable Cox proportional hazards models were then built to test whether LAEF, LAs, and LAVi predict all-cause mortality or time to transplant. The proportionality assumption test and supremum test for functional form were used to verify the model.

Results:
LA functional data on 656 patients were analyzed. Patients were followed for a median of 1900 days (5.2 years). There were 336 deaths and 17 transplants. LAEF and Las were significant predictors of outcome: HR=0.98, 95% CI [0.97, 0.99], p<0.001 , HR=0.94, 95% CI [0.91, 0.96], p<0.001) respectively. LAVi was not an independent predictor of survival after adjusting for the medical risk score (p=0.749). Multivariable Cox proportional analysis and ROC analysis for the prediction of death or transplant of the model within two years is shown in Figure 1.

Conclusion:
Left atrial function is a more powerful predictor of adverse outcome than left atrial size and ischemic mitral regurgitation. Further studies are needed to assess impact of treatment on LA function.
Abstract 12155: Detecting Peripheral Arterial Stenosis and Monitoring Atherosclerosis Severity
Authors: Heitner Tomer , Livneh Amit , Vargas Martha , Lorber Jonathan , Karmeli Ron , Landesberg Amir
Published: April 2022

Background:
The AHA guidelines recommend measuring the Ankle-Brachial Index (ABI) for assessing the severity of atherosclerosis. There is also an unmet need for early detection of peripheral artery stenosis to reduce morbidity and tissue loss. However, the sensitivity of ABI in detecting arterial stenosis is limited in the presence of arterial stiffening (arteriosclerosis), especially in diabetic and elderly patients, since arteriosclerosis yields fictitious higher ABI.
We hypothesize
that non-invasive quantification of the peripheral perfusion dynamics, instead of a single pressure point, can improve the diagnosis and differentiate between focal stenosis and general arteriosclerosis.

Methods:
Impedance plethysmography (IPG) were measured from the calf of patients that underwent peripheral revascularization, before and shortly after the interventions. The characteristic perfusion dynamics curves were derived from the cardiac complexes of the IPG that were recorded over at least 3 minutes. Successful interventions were defined according to the guidelines as a post-operational ABI increase of at least 0.15.

Results:
Twenty-four patients (60.9±9.3 years old, 16 (66.6 %) diabetics) that underwent above-knee revascularization were analyzed. The perfusion upstroke consisted of two characteristic phases: an initial slow phase followed by a fast vigorous rise. Improvement in the perfusion after the revascularization appeared only in the initial slow duration, denoted as the ‘Perfusion Deficit Index` (PDI). Of those, 15 (62%) had a successful intervention and the PDI decreased from 115±48 ms to 22±10 ms (p<0.0001) while the ABI increased from 0.53±0.26 to 0.94±0.22. In 9 limbs (37%) with unsuccessful interventions, there were no significant changes in PDI and ABI (from 143±31 ms to 117±40 ms and from 0.38±0.11 to 0.48±0.11, respectively). There was no significant change in the pulse transit time (p=0.19), a well-known index of arteriosclerosis, before and after the interventions.

Conclusions:
The PDI is a novel sensitive index for detection of focal arterial stenosis and it is independent of the severity of arteriosclerosis. This simple to use method can be used for monitoring atherosclerosis severity.
Abstract 12160: Predicting Atrial Fibrillation Recurrence After Thoracoscopic Ablation by Left Atrium Appendage Emptying Velocity
Authors: Bak Minjung , KIM Jihoon , Park Sung-ji , Kim Eun Kyoung , Jeong Dong Seop
Published: April 2022

Introduction:
Totally thoracoscopic ablation (TTA) is the latest tool for in patient with persistent or long-standing atrial fibrillation (AF). Left atrium appendage (LAA) emptying velocity is known related with maintenance sinus rhythm after successful cardioversion and catheter ablation. There were no studies about the value of LAA emptying velocity in thoracoscopic ablation since now.

Hypothesis:
We assessed the hypothesis that LAA emptying velocity could predict AF recurrence also in patient who underwent TTA.

Methods:
Between February 2012 and March 2015, 150 patients underwent TTA in a tertiary center in South Korea. The primary outcome was AF recurrence detection in either 12-lead electrocardiogram or holter during 3 years after TTA, excluding initial 3 months of blanking period. After baseline characteristics comparison between no AF recurrence group and AF recurrence group, main contributing factor for AF recurrence was analyzed with multivariable cox regression. Additionally, time-dependent ROC (receiver operating characteristic) analysis was done to estimate predictive power of LAA emptying velocity for AF recurrence.

Results:
Proportion of paroxysmal AF and LAA emptying velocity were higher in no AF recurrence group. LA volume size was larger in AF recurrence group. Except these values, other clinical characteristics like age, sex, underlying disease, CHA
2
DS
2
-VASc score, history of RFCA, use of antiarrhythmic drug or surgical method were not significantly different. In multivariable cox regression, female sex (HR 2.474, 95% CI [1.036-5.905], p value=0.041) and LAA emptying velocity (HR 0.941, 95% CI [0.915-0.967], p value<0.001) were meaningful contributing factor for AF recurrence. Also, LAA emptying velocity showed modest degree predictive performances for predicting AF recurrence (AUC 0.754, 95% CI [0.675 - 0.834])(figure 1).

Conclusions:
In conclusion, LAA emptying velocity could predict AF recurrence after TTA.
Abstract 12174: Valsartan Protects Both Cardiac and Lung Cells From SARS-CoV-2 Infection
Authors: Bastaroli Francesca , Mura Manuela , SAMMARTINO JOSE' CAMILLA , ferrari alessandro , CORLI MARZIA , Guarona Chiara , Percivalle Elena , Gnecchi Massimiliano
Published: April 2022

Background:
Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) disease (COVID-19) mainly affects the respiratory system, but cardiac complications occur very often. SARS-CoV-2 entry in host cells is mediated by the interaction between the viral Spike (S) glycoprotein and the host angiotensin-converting enzyme 2 (ACE2). The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) might influence the expression of ACE2 and viral infection, but not much is known about these interactions.

Aim:
To evaluate the effects of ACEIs and ARBs during active viraemia.

Methods:
We tested the ACEI Lisinopril (at 100nM and 500nM) and the ARB Valsartan (at 10uM and 50uM) for one week on two cell types: cardiomyocytes derived from hiPSC (hiPSC-CMs) as heart model and a lung epithelial cancer cell line (16HBE) as pulmonary model. The SARS-CoV-2 wild strain was inoculated in the two treated cell types for one hour. Cell viability was measured 72 hours after infection. Supernatants were collected and titrated to verify the presence of infectious virus using a micro-neutralization assay on VERO-E6 cells. Levels of ACE2 mRNA and protein content on cell lysates were quantified after each treatment by RT-qPCR and western blot, respectively.

Results:
ACEI and ARB at both concentrations affected the viability of neither hiPSC-CMs nor 16HBE cells in the absence of virus. Vice versa, viral infection significantly decreased viability of both hiPSC-CMs (-46%; p<0,01) and 16HBE (-19%; p<0,05). Viral titration revealed that SARS-CoV-2 replicated in both cell lines and was actively released in supernatants. Importantly, pre-treatment with Valsartan 50uM increased the viability of both hiPSC-CMs and 16HBE after infection, while Lisinopril and the lower dose of Valsartan had neutral effect. Of note, Valsartan 50uM treatment decrease ACE2 mRNA level in both hiPSC-CMs (-47%, p<0,01) and 16HBE (-37%, p<0,01). Also ACE2 protein levels were reduced in cell lysates of hiPSC-CMs and 16HBE treated with Valsartan 50uM.

Conclusion:
These data suggest that ACEIs and ARBs do not worsen the SARS-CoV-2 infection. On the contrary, Valsartan seems to be protective against SARS-CoV-2 infection, possibly by reducing ACE2 expression.
Abstract 12187: Arrhythmia Substrate and Approaches for First-Time and Repeat Catheter Ablation in Patients With D-transposition of the Great Arteries and Atrial Baffles
Authors: Chiriac Anca , Cheema Kamal Preet P , Giardi Davide , Espinosa Samantha , Fitzgerald Patrick , Umadat Goyal , Perez-Downes Julio , Phillips Sabrina D , Madhavan Malini , Asirvatham Samuel , McLeod Christopher J
Published: April 2022

Introduction:
Atrial arrhythmias are common in patients with D-TGA and atrial switch. We sought to analyze the arrhythmia substrate and catheter ablation approaches and outcomes.

Methods:
We performed a retrospective review of all clinical and procedural data in patients with D-TGA followed at a large tertiary care center.

Results:
In a cohort of 152 patients (mean age 30±11 years), atrial tachycardia was present in 69(45%) patients. Ablations were performed in 39(26%) patients: macro-reentrant atrial flutter (N=37), atrial fibrillation (N=4), and focal automatic atrial tachycardia (N=3). Detailed electrophysiology study data was available for 34 patients. At first ablation (N=28), cavo-tricuspid isthmus dependent flutter (CTI, 23(82%)) was most common, followed by right atriotomy-related flutter (IART, 16(57%)) and focal atrial tachycardia (FAT, 1(3.5%)). Bidirectional CTI block often required ablation on both sides of the baffle to complete the isthmus line. Access to the pulmonary venous atrium was obtained in 82% of first-time ablations (via retrograde aortic access, 74%, baffle puncture, 6%, or baffle fenestration, 12%) and in 100% of redo procedures. The first ablation was acutely successful in 25 (89%) patients; the other 3 patients had either partial procedural success (1), failed ablation (1), or underwent an empirical ablation (1). Long-term arrhythmia recurrence occurred in 13(46%) after the first ablation and class III antiarrhythmic medications were utilized in 12 patients. At least one long-term recurrence occurred in 11(44%) patients. Importantly, clinical arrhythmia burden was significantly reduced post-ablation, with rare and short-limited episodes amenable to antiarrhythmic drugs or cardioversion. Repeat ablation was required in 3 cases. Long-term arrhythmia recurrence after a previously completed CTI line involved different arrhythmia mechanisms: scar-related reentry (80%) and automatic atrial tachycardia (40%).

Conclusions:
Atrial arrhythmia in patients with D-TGA often involves the CTI and atriotomy scars. Ablation of the CTI typically requires access to the pulmonary venous atrium to achieve bidirectional block. Despite late recurrence, the clinical arrhythmic burden is substantially improved.
Abstract 12190: The Role of Lipid Core Burden Index Measured by Near-Infrared Spectroscopy in Predicting Slow TIMI Flow After Coronary Intervention
Authors: Lim Subin , Cha Jung-Joon , Joo Hyung Joon , Park Jae Hyoung , Yu Cheol Woong , Ahn Tae Hoon , Lim Do-Sun , Hong Soon Jun
Published: April 2022

Background:
Decreased TIMI flow following percutaneous coronary intervention (PCI) is associated with poor clinical outcomes. However, predicting slow TIMI flow after PCI is limited. Herein, we investigated predicting slow TIMI flow based on the lipid core burden (LCB) of target lesion by using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS).

Methods and Results:
This study retrospectively evaluated 636 patients who underwent NIRS-IVUS guided PCI from a single tertiary center registry. Total patients were divided into decreased TIMI flow group (n=90, TIMI 0, 1, and 2) and normal TIMI flow group (n=546, TIMI 3). The extent of LCB in the treatment zone was calculated as the maximal LCB index (maxLCBi) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. In three-month composite events including all-cause death, myocardial infarction, stent thrombosis, and re-intervention, decreased TIMI flow group showed worse clinical outcomes compared to normal TIMI flow group (5.6% vs. 1.5%, log-rank p=0.010). To investigate the correlation between TIMI flow and lipid core burden, a receiver-operating characteristic analysis was performed, and a high LCBi group was defined as maxLCBi
4mm
≥353. Multivariate logistic regression analysis revealed that high LCBi group was strongly associated with decreased TIMI flow (OR 2.223, 95% CI 1.341-3.685, p=0.002).

Conclusions:
High LCBi measured by NIRS-IVUS could be considered an independent predictor for decreased TIMI flow. Furthermore, a high value for LCBi could lead to worse clinical outcomes.
Abstract 12197: Rural Caregivers With Low Health Literacy Show Greater Improvements in Diet Quality From a Cardiovascular Disease Risk Reduction Intervention Designed to Address Low Health Literacy Than Those With High Health Literacy
Authors: Kang Junghee , Chung Misook L , Biddle Martha J , Lennie Terry A , Miller Jennifer , Moser Debra K
Published: April 2022

Introduction:
Rural caregivers of those with chronic illnesses have higher cardiovascular disease (CVD) risk than urban caregivers. Diet is a major lifestyle factor that contributes to CVD risk. We conducted a randomized controlled trial of a CVD risk reduction intervention called Rural Intervention for Caregivers’ Heart Health (RICHH), that was designed to promote CVD risk reduction, including healthy eating and that was designed to be accessible to those with low health literacy (HL). We tested the moderating effect of HL on the impact of the intervention on diet quality.

Hypothesis:
Rural caregivers with low HL would gain equal or greater benefits from the RICHH intervention on diet quality compared to those with high HL.

Methods:
The newest vital sign (NVS), rural-urban commuting area (RUCA) code ≥4 or living in Appalachian counties, and Healthy Eating Index-2015 (HEI-2015) were used to determine HL, rurality, and diet quality, respectively. The HEI-2015 was computed based on a food frequency questionnaire at baseline and post-intervention. The RICHH intervention was delivered using videoconference technology by nurse interventionists once a week for 12 weeks. A linear mixed effect model was used to evaluate the moderation effect of HL (NVS ≥ 4) on the impact of the intervention on diet quality.

Results:
A total of 296 rural caregivers (54.5 ± 13.7 years old, 76% female) completed the study. The improvement in HEI-2015 scores was greater in the low HL group than in the high HL group controlling for age and sex (beta estimate = 9.21, SE = 3.31,
P
= 0.0058).

Conclusions:
The RICHH intervention was effective in improving diet quality of rural caregivers compared to the control group. In particular, rural caregivers with low HL benefited more from the intervention aimed at increasing diet quality. Thus, addressing low HL could play an important role to improve diet quality and to reduce CVD risk among caregivers residing in rural environment.
Abstract 12204: Factor Xa Inhibitors but Not Vitamin K Antagonists Are Associated With Lower Risk of Mortality After Index Peripheral Endovascular Intervention
Authors: Henkin Stanislav , Gladders Barbara , Young Michael , Goodney Philip P
Published: April 2022

Introduction:
Peripheral endovascular intervention (PVI) has become more common than surgical bypass for patients with peripheral artery disease (PAD). While low-dose rivaroxaban is associated with lower risk of major adverse limb events, full-dose anticoagulation may be necessary for other indications.

Hypothesis:
We hypothesized that, compared to Vitamin K antagonists, Factor Xa inhibitors are associated with lower risk of adverse events after PVI.

Methods:
We analyzed patients who underwent index PVI in the Vascular Quality Initiative (2010-2016) and linked outcomes to Medicare claims data. Using multivariable regression modeling, we then examined the association between discharge anticoagulation and prespecified outcomes (all-cause mortality, re-intervention, lower limb amputation).

Results:
Among 10,165 patients undergoing PVI, 1497 (14.7%: 11.7% Vitamin K antagonist, 1.3% Factor Xa inhibitors, 1.7% other anticoagulant) were discharged on an anticoagulant. Patients on an anticoagulant were older and more medically complex (e.g. coronary artery disease, congestive heart failure, diabetes); more likely to undergo urgent/emergent procedure with infrapopliteal treatment; and more likely to be discharged without an antiplatelet agent. Anticoagulation was associated with significantly higher risk of mortality (OR 1.8, 95% CI 1.2-2.1, p<0.001) and amputation (OR 1.4, 95% CI 1.2-1.6). In multivariate regression modeling, Factor Xa inhibitors were associated with lower risk of death (OR 0.61, 95% 0.39-0.95), while Vitamin K antagonists were associated with higher risk of death (OR 1.28, 95% CI 1.1-1.5). Similar trends were observed for re-intervention and lower limb amputation, although not statistically significant.

Conclusions:
Compared to Vitamin K antagonists, the use of Factor Xa inhibitors post-PVI is associated with lower risk of death. Further studies are necessary to evaluate the mechanism of this effect.
Abstract 12207: Impact of Residual Pulmonary Stenosis on the Prognosis After Pulmonary Valve Replacement for Pulmonary Regurgitation
Authors: Tominaga Yuji , Taira Masaki , Watanabe Takuji , Hasegawa Moyu , Ueno Takayoshi , Miyagawa Shigeru , Sawa Yoshiki
Published: April 2022

Introduction:
Pulmonary valve replacement (PVR) for pulmonary regurgitation (PR) was reported to provide beneficial effects on patients late after repair of tetralogy of Fallot (TOF). However, the impact of the degree of residual pulmonary stenosis (PS) in patients with severe PR remains unclear. Furthermore, the assessment of residual PS was difficult in patients with reduced RVEF. This study aimed to identify the impact of residual PS on the incidence of cardiovascular adverse events after PVR in preserved RVEF (pEF) or reduced RVEF (rEF) patients with PR late after repair of TOF.

Methods:
This was a single-center, retrospective review of 64 patients (56 repaired TOF-PS and 8 repaired TOF-pulmonary atresia) who underwent PVR for moderate to severe PR between 2003 and 2020. The threshold dividing pEF and rEF was 40%. Regarding residual PS, the definition the pressure gradient at the pulmonary valve in PSR group was 25 mmHg or more and less than 50mmHg. Patients were divided into 4 groups according to RVEF and the degree of residual PS (20 in PR-pEF, 12 in PSR-pEF, 25 in PR-rEF, 7 in PSR-rEF). Cardiovascular adverse events included cardiac death, prosthetic valve dysfunction, arrhythmia requiring treatment, and hospitalization for heart failure. Based on the above, the influence of hemodynamic parameters before PVR was analyzed.

Results:
The median follow-up period was 6.1 years [interquartile range 2.7-10]. There was no cardiac death and prosthetic valve dysfunction. Two patients died due to non-cardiac reason. Twenty-two (34%) patients showed cardiovascular adverse events. The cardiovascular adverse event-free rates were the highest in PSR-pEF group (100% at 5 years) and the lowest in PSR-rEF group (43% at 5 years) after PVR (log-rank p < 0.01), and 60% in PR-pEF and 70% in PR-rEF. In comparison between PSR groups, PSR-rEF had higher RVEDP (8±2 vs 13±2 mmHg, p < 0.01) and larger RAVI (71±25 vs 105±42 ml/m
2
, p=0.043).

Conclusion:
Patients with PSR-rEF had a high incidence of cardiovascular adverse events, high RVEDP, and large RAVI, suggesting RV adverse remodeling. The association between the degree of residual PS and RVEF should be taken into consideration on deciding the timing of PVR for PR.
Abstract 12208: Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity With County-Level COVID-19 Incidence and Outcomes in the United States
Authors: Islam Shabatun , Nayak Aditi , Hu Yingtian , Mehta Anurag , Dieppa Katherine , Almuwaqqat Zakaria , Ko Yi-An , Patel Shivani , Goyal Abhinav , Sullivan Samaah , Lewis Tene , Vaccarino Viola , Morris Alanna A , Quyyumi Arshed A
Published: April 2022

Background:
The COVID-19 pandemic adversely affected socially vulnerable and minority communities in the US initially, but the temporal trends during the year-long pandemic remain unknown.

Objective:
We examined temporal association between county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in US in the year starting in March 2020.

Methods:
Counties (n=3091) with > 50 COVID-19 cases by March 6th, 2021 were included. Associations between SVI (and its subcomponents) and county level racial composition with incidence and death per capita were assessed using a negative-binomial mixed-effects model. This model was used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, county-level comorbidities, and environmental factors.

Results:
Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, p<0.001), and death per capita (1.04, (95% CI 1.04, 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by winter, a period that coincided with sharp increase in infection rates and mortality, and when counties with higher proportion of White residents were disproportionately represented (“third wave”). By Spring 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of Blacks also observed similar temporal trends in COVID-19-related adverse outcomes. Counties with greater proportion of Hispanics had worse outcomes throughout the duration of the analysis.

Conclusion:
Except for winter “third wave” when majority White communities had highest incidence of cases, counties with greater social vulnerability and higher minority populations, experienced worse COVID-19 outcomes.
Abstract 12222: The Role of Metformin in Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis
Authors: Dewangga Raditya , Winston Kevin , Ilhami Lazuardi Gayu , Indriani Suci , Siddiq Taofan , Adiarto Suko
Published: April 2022

Introduction:
Abdominal aortic aneurysm (AAA) is a cardiovascular disease with very high mortality especially due to its tendency to be asymptomatic. Some reports suggest that patients with diabetes, especially those who take metformin, may be negatively associated with AAA, but the association is still unclear. Hence, we aim to conduct a systematic review with meta-analysis on the role of metformin in reducing AAA diameter progression and AAA-related events.

Hypothesis:
We hypothesized that metformin reduces the growth of AAA diameter and AAA-related events.

Methods:
A comprehensive search of relevant articles was systematically performed on PubMed, Science Direct, Cochrane, and Scopus for studies comparing metformin with no metformin treatment on patients with AAA. Two reviewers independently assessed the abstracts and full-text articles. The outcome was aortic enlargement progression and AAA-related events such as AAA rupture and mortality. Biases in selected studies were assessed using Newcastle-Ottawa Scale. Data from eligible studies were pooled for effect estimates. Statistical analysis was performed using Review Manager software.

Results:
A total of 11 articles comprising 110,727 patients were included in the systematic review. Results showed that metformin was associated with reduction of annual AAA diameter progression (weighted mean difference: -0.84 mm; 95%CI: -1.33 to -0.35; p: 0.0007; I
2
: 85%). Metformin treatment may be associated with a decrease in AAA-related events. Funnel plot analysis showed that there was an indication of publication bias.

Conclusions:
Our results may suggest a potential role for metformin in limiting AAA growth. Further randomized controlled trials are needed to confirm the results.
Abstract 12223: Prognostic Significance of Hyperkalemia in Chronic Heart Failure Patients With Implantable Cardioverter-Defibrillator
Authors: Kishihara Makoto , Hattori Hidetoshi , Suzuki Atsushi , Kikuchi Noriko , Minami Yuichiro , Shoda Morio , Hagiwara Nobuhisa
Published: April 2022

Introduction:
Hyperkalemia is a common morbidity in heart failure (HF) patients and potentially leads to the lethal arrhythmia. However, whether hyperkalemia is associated with worse outcome in chronic HF patients with Implantable Cardioverter-Defibrillator (ICD) is unknown.

Methods:
This was a retrospective review of all HF patients (n=532) who had been implanted with ICD from 2008 to 2017 at our institution. We examined the association of hyperkalemia with all-cause mortality, hospitalization for HF and appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation.

Results:
Hyperkalemia (≥5.0 mmol/L) were present in 48 patients (9%) and normokalemia (3.5 to 4.9 mmol/L) in 476 patients (89%). The median potassium levels were 5.2 mmol/L [interquartile range (IQR) 5.0-5.3] in the hyperkalemia group and 4.2 mmol/L (IQR 4.0-4.5) in the normokalemia group. Mean follow-up was 1,602 days. The Kaplan-Meier analysis showed there were no significant between-group differences in all-cause mortality and appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation (log-rank
P
= 0.10 and
P
= 0.97, respectively). However, in hyperkalemia group there was a significant higher rate of hospitalization for HF (log-rank
P
= 0.0002). Cox regression analysis after adjustment for significant predictors demonstrated that hyperkalemia was independently associated with hospitalization for HF compared with normokalemia.

Conclusion:
In chronic HF patients with ICD, hyperkalemia is an independent predictor of hospitalization for HF, but hyperkalemia is not associated with increased risk of ventricular tachycardia or ventricular fibrillation.