bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13686: Increased Right Superior Pulmonary Vein Ovality is Associated With Phrenic Nerve Injury in Patients Undergoing Cryoablation for Atrial Fibrillation
Authors: Vaishnav Aditi S , Coleman Kristie M , Makker Parth , Saleh Moussa , Bhasin Kabir , Bernstein Neil , Skipitaris Nicholas T , Mountantonakis Stavros E
Published: November 2020

Introduction:
Success of cryoablation for atrial fibrillation (AF) requires creation of continuous, circumferential lesions around the pulmonary veins (PVs). The depth of these cryo-lesions depends on tissue contact, balloon location, ablation duration and nadir temperature. An optimum lesion depth must be achieved such that effective isolation occurs without collateral cryothermal damage to surrounding structures eg, phrenic nerve injury (PNI).

Hypothesis:
Increased RSPV ovality results in poor pairing between the balloon and PV, which may cause deeper freezing at the lateral circumference of the PV antrum, near the course of the phrenic nerve, resulting in PNI.

Methods:
Consecutive patients undergoing cryoablation for paroxysmal/persistent AF were included. Pre-procedural cardiac CT scans were analyzed to evaluate PV size (diameters, cross-sectional area, circumference) and ovality (ratio of maximum:minimum diameter (d
max
:d
min
), shape). Effects of these anatomic characteristics on rates of complications were analyzed.

Results:
RSPVs from 310 patients (age 65.2 years, 38.1% female, 43.2% persAF) were studied. RSPVs were the largest of the 4 normal PVs (d
max
21.5±4 mm; d
min
17.8±3.8 mm; area 309±113 mm
2
; circumference 124.2±22.8 mm). A majority of RSPVs were round (57.3% round, 26.9% oval and 15.9% flat), with median d
max
:d
min
= 1.18 [1.1-1.32].

PNI was the 2nd most common complication (after access-site complications). Transient diaphragmatic palsy occurred in 2.9% of patients; there were no cases of complete or persistent diaphragmatic paralysis.

Patients in whom diaphragmatic palsy occurred had more oval veins (median d
max
:d
min
1.35 [1.23-1.5] vs 1.18 [1.1-1.31]; p=0.015). Additionally, there was a significant difference in the proportion of patients with round RSPVs who had diaphragmatic palsy (1.1%) compared to those with oval or flat RSPVs (5.3%) (p=0.029) (Fig).

Conclusion:
Increased RSPV ovality is associated with phrenic nerve injury.
Abstract 13695: Paracrine-mediated Rejuvenation of Aged Mesenchymal Stem Cells Involves Broad Transcriptional Modulation of Angiogenic Factors
Authors: Hung George , Barth Andreas S , Johnston Peter V , Gerstenblith Gary
Published: November 2020

Introduction:
Angiogenesis induced by bone marrow mesenchymal stem cells (MSCs) obtained from aged mice is inferior to those obtained from young mice, but is improved following exposure to conditioned media (CM) from young MSCs. To define alterations in gene expression and signaling pathways underlying the observed angiogenic improvement, we characterized differences in cellular mRNA expression between “non-rejuvenated” and “rejuvenated” (exposed to CM from young MSCs) old MSCs.

Methods:
Replicates of 105 MSCs isolated from old (18-24 months) C57BL mice (n=6) were cultured separately, or in co-culture with MSCs from young (4-6 weeks, n=6) mice using 0.4μm Transwell plates that allow transfer of soluble factors, but not of cells. After 7d in culture, mRNA from old and rejuvenated MSCs was isolated and sequenced. Analysis was performed using open source Galaxy pipeline. Transcription factor (TF) and miRNA target enrichment analyses were performed using ChEA3 and MIENTURNET.

Results:
Of the 529 unique transcripts involved in angiogenesis (GO-ID 0001525), 98 differentially expressed transcripts (Bonferroni p < 0.0001) were identified. The rejuvenated MSCs showed significantly increased expression of 39 genes. The majority of these involved canonical angiogenic pathways and/or regulation of VEGF: JAK1, LOXL2, KLF4, BMP4, and ADM. Top enriched TFs and miRNAs included EPAS1 and miR-20a, respectively, both directly involved in VEGF signaling, along with SOX18, SNAI1, SOX7, miR-126a, and miR-499 (FDR < 0.05), all of which are known to promote either angiogenesis and/or stemness.

Conclusions:
Improved angiogenesis by old MSCs exposed to CM from young MSCs is accompanied by significant modulation of angiogenic mediators, crucial in both VEGF and non-VEGF signaling pathways. These changes suggest targets for transcriptional modification to improve angiogenesis and tissue repair in aged patients.
Abstract 13721: Is Single Dose Interruption of Direct Oral Anticoagulants Necessary Before Atrial Fibrillation Ablation? A Systematic Review and Meta-analysis
Authors: Jafry Ali H , Akhtar Khawaja H , Chaudhary Amna M , Khan Safi U , Khan Mohammad S , Lakkireddy Dhanunjaya R , Gopinathannair Rakesh , Asad Zain Ul Abideen
Published: November 2020

Background:
In patients with atrial fibrillation taking direct oral anticoagulants (DOACS) and undergoing catheter ablation, it is unclear if interruption of a single dose of DOAC before the procedure is necessary. We assessed the peri-procedural adverse events between uninterrupted vs single-dose interrupted DOACS.

Methods:
A systematic review of Medline and EMBASE was conducted and all randomized controlled trials (RCTs) and observational studies that compared uninterrupted versus interrupted DOACS were included. Random effects model was used and risk ratios (RR) with 95% confidence intervals (CI) were reported using Mantel Haenszel method. All studies defined dose interruption as holding a single dose of DOAC before ablation. Separate analyses were conducted for RCTs and observational studies.

Results:
Eight RCTs with 2656 patients and 4 observational studies with 834 patients were included. In RCT restricted analysis, no significant difference was seen in major bleeding [RR 0.65 (CI 0.30-1.42)], minor bleeding [RR 0.98 (0.68-1.40)], stroke/transient ischemic attack/thromboembolism [RR 0.90 (CI 0.27-2.98)] and silent cerebral infarction [RR 0.51 (CI 0.14-1.89)]. In observational study restricted analysis, no significant difference was seen in major bleeding [RR 3.04 (CI 0.13-74.07)], minor bleeding [RR 0.88 (0.46-1.69)], stroke/transient ischemic attack/thromboembolism [RR 0.98 (CI 0.12-7.91)] and a statistically significant lower silent cerebral infarction [RR 0.45 (CI 0.31-0.67)].

Conclusion:
Uninterrupted DOACS are safe for patients undergoing AF ablation and logistically easier for patients.

Figure 1: Forest plot showing outcomes with uninterrupted vs interrupted direct oral anticoagulants in patients undergoing ablation for atrial fibrillation in randomized controlled trials.
Abstract 13732: Evaluation of the Mechanical Effect of Thickened IPS Derived Cardiomyocyte Patch on the Distressed Left Ventricle Using Cardiac Simulator “Ut-heart”
Authors: Masuda Hirotada , Miyagawa Shigeru , Washio Takumi , Sugiura Seiryo , Okada Jun-ichi , Ueno Takayoshi , Toda Koichi , Kuratani Toru , Hisada Toshiaki , Sawa Yoshiki
Published: November 2020

Introduction:
iPS cell-derived cardiac cell sheet (iPS sheet) transplantation is expected to have both cytokine paracrine effect and mechanical effect on the failed heart. In order to clarify the latter effect, we utilized the cardiac simulator “UT-Heart” to quantitatively evaluate the improvement of pumping function of the left ventricle with myocardial infarction covered by the thickened iPS sheet in silico. The direct mechanical impact of iPS sheet with various thicknesses was calculated first, and then the remodeling effect of fiber orientation was investigated.

Patient and Method:
An infarcted heart model based on the actual patient’s data was created on the computer and an iPS sheet was virtually implanted under the following assumptions: (1) electrophysiologically synchronized with the underlying cardiac muscle, (2) covered the infarct area entirely, (3) the fiber orientation of sheet was parallel to that of the epicardial tissue when attached, (4) if remodeling occurs, the fiber orientations of myocardial tissue and the attached sheet change such that the contraction force and the fiber strains are homogenized in the heart. The UT-Heart simulation was performed while changing iPS sheet thickness from 1mm to 5mm.

Results:
The LVEF of 18.0 % at pre-implantation was improved to 18.5 % with 1 mm thickness, and 19.6 % with 5 mm thickness without remodeling assumption as shown in the left of the figure. If LV remodeling occurs, the LVEF was improved to 20.9 % with 1mm thickness and 22.8 % with 5mm thickness. The LVESP was 10 mmHg higher than that of pre-implantation even when 1mm thickness was implanted.

Conclusion:
The direct mechanical effect of the thickened iPS sheet on the distressed LV was quantitatively evaluated in silico. Because changes in fiber orientation have a significant impact on pumping function, the remodeling assumption used herein should be experimentally verified in the future.
Abstract 13735: Coronary Endothelial Dysfunction Plays Important Roles on Development of Acute Coronary Syndrome and Fatal Cardiovascular Events During Long-term Follow-up Over 10 Years
Authors: Murakami Tatsuaki , Ohsato Kazuo
Published: November 2020

Introduction:
Although coronary endothelial dysfunction is thought to affect coronary atherothrombogenic processes, there has been little practical evidence for the relationship between clinical evolution of fatal or non-fatal acute coronary syndrome (ACS) and coronary endothelial dysfunction.

Hypothesis:
We assessed hypothesis that coronary endothelial dysfunction has clinical impacts on development of ACS and fatal cardiovascular events.

Methods:
Coronary endothelial dysfunction was practically graded by the flow-mediated endothelium-dependent reactive changes in coronary artery diameter (CFMD) to infusion of adenosine triphosphate (ATP ; 50μg) into the normal left coronary artery using quantitative coronary arteriography in 150 patients with stable coronary artery disease. The enrolled patients were categorized into tertile groups according to the values of CFMD, and we prospectively followed-up major adverse clinical cardiac events including ACS and cardiovascular death.

Results:
For a mean follow-up period of 132 months (range; 120 to 144) with complete follow-up, the patients in the lower third with severe coronary endothelial dysfunction (Group-L) more frequently developed ACS than those in the middle third with mild coronary endothelial dysfunction (Group-M) plus those in the higher third without coronary endothelial dysfunction (Group-H) [Group-L versus Group-M plus Group-H: 15(30%) versus 5(10%) plus 0(0%), p<0.001, by Kaplan-Meier analysis]. Majority of the patients who resulted in cardiovascular death belonged to Group-L, [6(12%) versus 1(2%) plus 0(0%), p=0.014]. Cox hazard proportional model analyses indicated that severe coronary endothelial dysfunction was the strong predictor for future ACS (hazard ratio=7.53, 95%confidential interval; 1.78-12.25, p<0.001) and future cardiovascular death (hazard ratio=13.50, 95%confidential interval; 1.55-25.25, p=0.005).

Conclusions:
This is the novel and longest follow-up investigation that demonstrates coronary endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events and therefore the strategies based on status of coronary endothelial dysfunction are required to prevent major adverse ischemic cardiac events.
Abstract 13764: Chronic Electronic Cigarette Vapor Exposure Leads to Impaired Cardiac Function in Experimental Rat Myocardial Ischemia/reperfusion Model
Authors: Dai Wangde , Shi Jianru , Carreno Juan , Zhao Lifu , Kleinman Michael T , Herman David A , Johnson Rebecca M , Renusch Samantha , Hasen Irene , Ting Amanda , Kloner Robert A
Published: November 2020

Background:
We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI).

Methods:
After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Cardiac function was assessed by echocardiogram and pressure measurements of the aorta and left ventricle (LV). Cardiac output (CO) was measured using a thermodilution catheter. At 3 hours of reperfusion, ischemic risk zone, no-reflow and infarct areas were determined.

Results:
Prior to coronary artery occlusion, chronic eC exposure was associated with a lower CO (45 ± 2 ml/min ) compared to air (55 ± 4 ml/min; p<0.05)) and a decrease in +dP/dt (5226 ± 294 mmHg/s versus 6062 ± 271 mmHg/s; p=0.05). After 30 minutes of coronary occlusion and 2.5 hours of reperfusion, CO and LV + dp/dt fell in both groups, but remained significantly lower in eC compared to the pure air group (Table). LV systolic and diastolic dimensions were significantly smaller in the E-Cig group compared to the air group. Systolic and diastolic anterior LV wall thickness were significantly thicker in the eC group after reperfusion. The ischemic risk size was comparable between the 2 groups. MI size was 48.8 ± 4.8% of the ischemic risk zone in the air group and 45.4 ± 4.4 % in the eC group (p=0.603). The area of no reflow was 26.7 ± 4.0% of the ischemic risk zone in the air group and 21.1 ± 3.5% in the E-C group (p=0.298). Chronic eC exposure did not change heart rate and blood pressure, but the significantly increased the systemic arterial resistance.

Conclusions:
Chronic exposure to eC significantly impaired cardiac function in rats prior to and during ischemia/reperfusion, increased arterial resistance, but did not increase infarct size or no-reflow zone. Increased LV wall thickness of the risk zone suggested that eC may have increased edema.
Abstract 13768: Adoption and Effectiveness of an Mhealth Intervention for Hypertension in Older Adults: A Pilot Clinical Trial
Authors: Muldoon Matthew F , Einhorn Julian , Yabes Jonathan , Burton Danielle , Rollman Bruce , Irizarry Taya , Basse Jeanne , Burke Lora E , Kamarck Thomas , Suffoletto Brian
Published: November 2020

Introduction:
Hypertension is uncontrolled in 50% of diagnosed adults in the US, and especially in older adults. Home blood pressure monitoring (HBPM) can improve hypertension management by providing clinicians with up-to-date information on BP control and by improving patients’ adherence to prescribed medications and other healthy behaviors. MyBP is a patient-facing HBPM aide that provides video-based education and supports BP self-monitoring with recurring feedback using proactive, bidirectional, automated text messages. Summary reports are routed to primary care providers.

Hypothesis:
In this proof-of-concept, pragmatic clinical trial, we tested the hypothesis that MyBP will improve hypertension self-efficacy and lower BP in older adults.

Methods:
Community-dwelling adults ≥55 y/o with uncontrolled hypertension were recruited from primary care offices. Enrollees were provided a standard automatic BP cuff and randomized 2:1 to MyBP vs treatment-as-usual (control). Engagement with MyBP was defined as the proportion of BP reading prompts for which a reading was submitted, tracked over successive 2-week monitoring periods. Study BP data were acquired independently of MyBP from all participants by single-blind, phone-supervised home BP measurements.

Results:
Participants (N=62; 40 women, 33 Blacks, 38 without a college degree, mean age 66, mean office BP 164/91, mean # BP medications 2.6) were randomized to MyBP (41) vs. control (n=21). In the MyBP group, engagement with HBPM averaged over 80%, without notable attrition over the 5-month study period. Regression analyses revealed an interaction between baseline systolic BP and group assignment on change in systolic BP [interaction effect estimate -0.59 (-1.00, -0.19)], such that patients who had a higher baseline systolic BP and were assigned to MyBP showed a greater decline in systolic BP when compared to control patients. Hypertension self-efficacy also improved in the intervention group compared to controls [estimate 0.556 (0.104,1.008)].

Conclusions:
In this pragmatic, pilot clinical trial, older adults with hypertension used a novel mHealth technology at high levels, reported improved hypertension self-efficacy, and experienced a decline in BP if home BP was elevated at baseline.
Abstract 14062: Accuracy of Exercise Induced St- Elevation in Lead Avr in the Diagnosis of Significant Left Main or Proximal Left Anterior Descending Artery Stenosis: A Systematic Review
Authors: Bhatia Kirtipal S , Das Subrat , Krishnamurthi Nirupama , Aggarwal Devika , jain vardhmaan , Narasimhan Bharat , Martin Lily , Joshi Aditya , Kukar Nina
Published: November 2020

Introduction:
ST-segment changes during exercise stress testing are diagnostic of myocardial ischemia in patients with suspected coronary artery disease (CAD). Recent studies have shown that exercise-induced ST-elevation in aVR is associated with significant stenosis of the left main (LM) and proximal left anterior descending (pLAD) arteries

Methods:
Search of electronic databases (Embase, Medline, and Web of Science) using MeSH terms and keywords for exercise stress test, lead aVR and CAD was performed from inception through December 2019. 2 reviewers independently screened results in 2 stages: title/abstract followed by full text. Included studies had adult patients who underwent exercise stress testing and reported the performance of ST-elevation >1 mm in lead aVR for diagnosing significant LM or pLAD disease. Significant disease was defined as luminal narrowing >50% and >70% for LM and pLAD respectively. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios were calculated using a bivariate model, and a summary receiver operator curve (SROC) was constructed.

Results:
We included 6 studies with 1128 patients. The pooled sensitivity was 0.8 (95% CI 0.36-0.97; I
2
=94.7) and pooled specificity was 0.78 (95% CI 0.56-0.90; I
2
=97.8). Overall calculated positive LR was 3.56 (95% CI 2.34-5.4) and negative LR was 0.26 (95% CI 0.07-1.01). The pooled diagnostic odds ratio was 13.5 (95% CI 4.8-38.5). Hierarchical SROC curve showed an area under the curve of 0.84 (95% CI 0.81-0.87) (Figure 1).

Conclusions:
Our analysis showed moderate sensitivity and specificity of exercise-induced aVR ST-elevation for diagnosing significant LM or pLAD disease. The heterogeneity among studies was high, likely due to differences in patient selection. In conclusion, ST-elevation in aVR during exercise stress test increases the likelihood of having LM or pLAD disease. Large studies are needed to substantiate this finding.
Abstract 14082: The Effect of Diagnostic Ultrasound Mediated High Mechanical Impulses on Cardiac Output During an Ultrasound Enhancing Agent Infusion
Authors: Sundaravel Swethika , Roettger Jessica , Albulushi Arif , Olson Joan , Xie Feng , Porter Thomas R
Published: November 2020

Introduction:
Diagnostic ultrasound high mechanical index (MI) impulses are used during an ultrasound enhancing agent (UEA) infusion to improve endocardial border resolution and study myocardial perfusion. They have also been shown to cause endothelial shear, resulting in prolonged increases in ATP release and augment microvascular flow. The potential for these high MI impulses to alter cardiac output (CO) are unknown.

Hypothesis:
To study the impact of high MI impulses on CO

Methods:
Fifty one patients (mean age 63±15 years; 41% female) referred for contrast echocardiography underwent very low MI imaging with intermittent high MI impulses (1.6-1.7 Megahertz) in three different apical windows during either a Definity (Lantheus Medical) or Lumason (Bracco Diagnostics) infusion or bolus. CO was determined from Doppler measurements of left ventricular outflow tract stroke volume and heart rate. Mean contrast enhanced biplane left ventricular ejection fraction (LVEF) was 53±15%; (range 10-75%). CO from baseline without contrast (COwoC) and baseline after contrast (COwC) before high MI impulses were compared to CO after contrast and after high MI impulses (COaHMI). All CO measurements were made by an independent reviewer blinded to time of measurement (before or after high MI impulses).

Results:
Although heart rate did not change before and after intermittent high MI impulse administration, COaHMI increased significantly when compared to COwoC and COwC (p< 0.001 for both comparisons; Figure). In nine patients (18%), CO increased by more than 20%. In patients with LVEF < 40% COwC was 2.4±0.8 liters per minute (LPM) and COaHMI increased to 2.7± 0.8 LPM (p=0001). In patients with LVEF≥40%, COwC was 3.4±1.06 LPM while COaHMI increased to 3.8± 1.2 LPM (p=0.00001).

Conclusions:
Application of diagnostic guided high MI impulses during a commercially available microbubble infusion significantly increases CO irrespective of underlying left ventricular systolic function.
Abstract 14084: Albuminuria and Prognosis Among Individuals With Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (aric) Study
Authors: Mok Yejin , Ballew Shoshana , Stacey Richard , Rossi Joseph , Koton Silvia , Kucharska-newton Anna , Chang Patricia , Coresh Josef , Rosamond Wayne D , Matsushita Kunihiro
Published: November 2020

Background:
The AHA/ACC 2018 Cholesterol Guideline categorizes ASCVD patients into very high-risk vs. high-risk to guide intensive therapy. This categorization is based on clinical conditions, including reduced kidney function, but does not take into account albuminuria, the other kidney measure often available in clinical practice.

Methods:
We studied 838 participants with major ASCVD (myocardial infarction, ischemic stroke, or symptomatic peripheral artery disease) from the ARIC study at baseline (1996
-
98). We compared urine albumin-to-creatinine ratio (ACR) and the eight high-risk conditions of age 65+, reduced kidney function, diabetes, etc. in the AHA/ACC Guideline regarding their associations with composite outcome of all-cause mortality, myocardial infarction, ischemic stroke, and heart failure. We also evaluated risk classification by adding ACR to the eight high-risk conditions.

Results:
During a median follow-up of 8 years, 724 (86%) participants developed a composite outcome. ACR ≥30 mg/g was associated with the composite outcome (adjusted hazard ratio [aHR] 1.45 [95% CI 1.20, 1.75]) beyond the eight high-risk conditions (aHR of these conditions ranged from 0.96 to 2.46). The addition of ACR improved the c-statistic by 0.011 (95% CI 0.003-0.019) from 0.661 to 0.672. ACR classified 4.6% of high-risk group to very high-risk and 11.2% of very high-risk group to extremely very high-risk with a reasonable calibration (Figure). Even ACR ≥10 mg/g showed a significant aHR of 1.38 (1.17, 1.63) and classified 13.4% of high-risk and 18.1% very high-risk to a higher risk category. Of our patients with ASCVD, 77% had diabetes, hypertension, or low kidney function, clinical conditions in which the ACR assessment is recommended.

Conclusions:
In ASCVD, albuminuria was a strong predictor of major adverse cardiovascular outcome and improved risk prediction. Clinicians should pay attention to albuminuria, in addition to eGFR, when managing ASCVD patients.
Abstract 14088: Pro-neurotensin/neuromedin N is Associated With Incident Metabolic Syndrome
Authors: Nicoli Charles D , Carson April P , Plante Timothy B , Long Leann , McClure Leslie A , Schulte Janin , Cushman Mary
Published: November 2020

Introduction:
The tridecapeptide neurotensin increases dietary fatty acid uptake and is implicated in insulin resistance in animal models and—through plasma levels of its stable precursor pro-neurotensin/neuromedin N (pro-NT/NMN)—with human diabetes mellitus, obesity, and cardiovascular disease. We evaluated the association of pro-NT/NMN with incident metabolic syndrome (MetS).

Methods:
This analysis included a subcohort of 2,770 Black and White participants without prevalent MetS at baseline (2003-2007) from the REasons for Geographic And Racial Differences in Stroke study who had fasting plasma pro-NT/NMN measured by immunoassay and completed a second assessment from 2013-2016. Incident MetS was defined as ≥3 harmonized criteria at follow-up: impaired glycemic control, high systolic blood pressure, high triglycerides, low high-density lipoprotein (HDL), and increased waist circumference. Four sequential weighted logistic regression models were fitted to incident MetS overall and for each criterion separately, incorporating demographic factors, metabolic risk factors, HOMA-IR, and diet scores.

Results:
Over mean 9.4 (standard deviation [SD] 1.0) years follow up, 564 participants developed MetS. Median [IQR] plasma pro-NT/NMN was 160 [118-218] pmol/L. In the overall group, higher log pro-NT/NMN was associated with incidence of lower HDL (odds ratio [OR] per SD pro-NT/NMN 1.16, 95% confidence interval [CI] 1.00-1.35) and impaired glycemic control (1.25, 95% CI 1.11-1.40), but not other MetS components. Each SD higher log pro-NT/NMN was associated with a 22% increased odds of incident MetS, adjusted for demographics (Table); this was not significant when controlling for HOMA-IR in all but the White subgroup (race
p
-interaction 0.05). No differences by sex were observed.

Conclusions:
Higher neurotensin likely augments insulin resistance to increase odds of incident metabolic syndrome through impaired glycemic control and lower HDL.
Abstract 14089: Reduced Pain External Defibrillation (RPD) and MRI-conditional RPD: Reduced Pain ind Equivalent Efficiency Validation in Swine
Authors: Schmidt Ehud J , Elahi Hassan , Baumgaertner Ryan , Halperin Henry R
Published: November 2020

Introduction:
External defibrillators are used for cardioversion and resuscitation after sudden cardiac arrest (SCA). External defibrillators are also required for emergency MRI (acute stroke, spinal trauma). Low-power (9 Joule) ICD RPDs [1], and MRI-conditional external defibrillator prototypes exist [2]. An RPD external defibrillator was constructed, consisting of a Zoll defibrillator integrated with a tetanizing unit. The tetanizing waveform slowly compressed chest musculature prior to the strong biphasic defibrillating pulse, reducing chest contraction during the biphasic pulse, the major pain source. This RPD system (Fig. 1A-D) was evaluated for pain reduction and defibrillation effectiveness in swine.

Method:
The tetanizing unit consisted of a programmable generator that delivered a triangular 1-KHz pulse of 250-2000msec duration and 10-100 Volt peak amplitude, and subsequently triggered the conventional defibrillator to send out standard short (8msec) powerful (20-400 J) biphasic pulses. Forward limb motion (Fig. 1E), an established pain measure [3], was evaluated by measuring limb acceleration, acceleration rate and work (energy). 5 swine were arrested electrically and then defibrillated. RPD was repeated 15-20 times/swine, varying tetanizing parameters and biphasic energy.

Results:
Fig. 1F-H compare an RPD defibrillation and equivalent biphasic defibrillation, showing smaller accelerations and acceleration rates. Fig. 1J shows work results, at 30-200J biphasic energy, demonstrating an 83

+

15% limb work reduction with the RPD waveforms. Optimal tetanizing parameters were 15-25V amplitude and 500-750msec duration. Rhythm recovery for RPD and conventional defibrillation was identical.

Conclusions:
Reduced pain defibrillation may allow cardioversion without anesthesia and faster defibrillation after SCA.
References:
[1] Hunter DW 2016. [2] Schmidt EJ 2016. [3] Boriani G, 2005.
Abstract 14105: Geographic Variation in Infant Mortality Due to Congenital Heart Disease
Authors: Udine Michelle , Evans Frank , Burns Kristin M , Pearson Gail D , Kaltman Jonathan
Published: November 2020

Background:
Geographic variation in ischemic heart disease and stroke mortality is well-known and likely mediated by health care access, environmental, and sociodemographic factors. Little is known, however, about geographic variation in infant mortality due to congenital heart disease (CHD-IM). This study examines county-level estimates of CHD-IM to understand geographic patterns and factors that may influence variation in mortality.

Methods:
In this cross-sectional population-based study, we used linked live birth-infant death cohort files from the National Center for Health Statistics containing live births from 2006 to 2015 with cause of death attributed to congenital heart disease. Hierarchical Bayesian models were used to estimate CHD-IM rate for all US counties (N=3,142). Model based estimates were mapped to explore geographic patterns. Covariates included sex, maternal race and ethnicity, percentage of the county population below the poverty level, and proximity of the county to a US News and World Report top 50 ranked pediatric cardiac center (PCC).

Results:
From 2006 to 2015, there were 13,987 infant deaths due to congenital heart disease and 40,847,089 live births, giving an unadjusted CHD-IM rate of 0.34/1,000 live births. In our model, decreased mortality risk correlated with close proximity to a top 50 PCC, while increased mortality risk correlated with higher level of poverty. The figure shows predicted CHD-IM rates by county. Kentucky and Mississippi had the greatest proportion of counties with a predicted CHD-IM rate > 95th percentile. All counties in Connecticut, Massachusetts, and Rhode Island had a predicted CHD-IM rate < 5th percentile.

Conclusion:
Analyzing county-level variation of CHD-IM reveals patterns that can help to identify health care disparities and inform local efforts to understand and address variation in outcomes of infants born with congenital heart disease.
Abstract 14134: The Impact of Ablation for Atrial Fibrillation on Dementia Incidence in Patients With and Without Depression
Authors: May Heidi T , Bair Tami L , Knight Stacey , Anderson Jeffrey L , Muhlestein Joseph B , Knowlton Kirk U , Horne Benjamin D , Bunch T Jared J
Published: November 2020

Introduction:
Studies have previously shown that atrial fibrillation (AF) is associated with dementia. The mechanisms are likely multifactorial, but may involve treatment strategies that include anticoagulation use and rhythm management, particularly when used early. Patients that have earlier-life depression are at risk of dementia. However, depression diagnosis in AF patients may indicate a patient at higher risk of developing dementia and whether treatments ameliorate that risk is unknown.

Methods:
A total of 132,703 AF patients without a history of dementia were studied. History of depression was determined at the time of AF diagnosis. Patients were deemed as having a follow-up ablation if it occurred prior to a dementia diagnosis. Patients were stratified into 4 groups based on depression history and follow-up ablation status: no depression, ablation (n=5,960); no depression, no ablation (n=106,986); depression, ablation (n=923); and depression, no ablation (n=18,834). Patients were followed for 5-year incidence of dementia.

Results:
A total of 14.9% (n=19,757) pts had a history of depression at the time of AF diagnosis. The mean time between depression and AF diagnoses was 4.9±4.8 years. Patients with depression were younger (68±15 vs. 71±14 years), more likely to be female (62% vs. 44%), and had more cardiovascular comorbidities. Mean time to ablation was 1.3±1.4 days (median: 7.7 months) from AF diagnosis. Frequencies of 5-year dementia were: no depression, ablation=1.6%; no depression, no ablation=5.2%; depression, ablation=4.7%; and depression, no ablation=9.7%, p<0.0001. Multivariable comparisons between the groups are shown in the Figure.

Conclusion:
In AF patients with and without depression, ablation was associated with a lower risk of incident dementia. Rhythm control approaches that improve long-term brain perfusion may represent a means to impact cognitive declines in patients at higher risk because of earlier-life depression.
Abstract 14141: A Contemporary Assessment of Lipid Lowering Therapies and Low-density Lipoprotein Cholesterol in Peripheral Artery Disease
Authors: Hess Connie N , Cannon Christopher P , Beckman Joshua A , Goodney Philip , Patel Manesh R , Shannon Erin , Orroth Kate K , Mues Katherine E , hiatt william R , Bonaca Marc P
Published: November 2020

Introduction:
Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Strategies that lower LDL-C levels reduce this risk.

Hypothesis:
We hypothesized that real-world PAD patients are overall undertreated with lipid lowering therapies (LLT) but that LLT use and achieved LDL-C are improved in high risk patients with ischemic events.

Methods:
Patients with PAD in the MarketScan database linked to PROGNOS lab data from January 1, 2014 through December 31, 2018 were examined. Outcomes included use of LLT, defined as high intensity (HI) (high intensity statin, any statin plus ezetimibe, or any use of a PCSK9 inhibitor), low intensity (LI) (any other lipid regimen), or no therapy, and follow up LDL-C level. Goal LDL-C was defined as <70 mg/dl.

Results:
Among 18,747 PAD patients, 25% were on HI LLT, 43% were on LI LLT, and 32% were on no therapy at baseline (Figure A). The median LDL-C was 91 mg/dl (IQR 70, 118), and 25% of patients were at goal (Figure B). After a median follow up of 18 months, use of HI LLT increased by 4%, the median LDL-C decreased by 5 mg/dl, and an additional 3% of patients were at goal LDL-C. Greater use of HI LLT was observed among patients with a MACE (55%) or MALE (41%) event during follow up compared with patients without an ischemic event (26%) during follow up (Figure C). Follow up LDL-C levels remained above goal for most patients (post-MACE: median LDL-C 77 mg/dl, 42% patients at goal; post-MALE: median LDL-C 80 mg/dl, 36% patients at goal).

Conclusions:
In PAD patients, use of LLT is suboptimal, and LDL-C levels remain elevated. After an ischemic event, LLT use is intensified, with greater use of HI LLT observed after MACE than MALE. Despite this, LLT remains underutilized, with >50% of patients not at goal LDL-C. Strategies to better implement proven therapies to reduce risk in this high risk population are needed.
Abstract 14164: Trends in U.S. Spending on Diabetes Therapies by Insurance Payer From 2007 to 2017
Authors: Chiu Nicholas , Aggarwal Rahul , Wadhera Rishi , Shen Changyu , Yeh Robert W , Kazi Dhruv
Published: November 2020

Importance:
Diabetes mellitus is an important cardiovascular risk factor, and diabetes therapies are among the most commonly prescribed medications in the U.S. While the introduction of new, high-cost therapies has increased costs, recent trends in national spending on diabetes medications by insurance payer have not been examined. Understanding the burden of costs amongst all payers may help inform strategies to optimize drug expenditures in the US.

Objective:
To produce nationally representative estimates of US spending on diabetes therapies from 2007 to 2017, stratified by insurance payers (Medicare, Medicaid, Private, VA, and TRICARE—a program for civilian health benefits for US Armed Forces). Trends in out-of-pocket costs were also examined.

Design/Setting:
Retrospective analysis of patient-level data from the Medical Expenditure Panel Survey, a nationally representative survey that is the most complete source of data on healthcare costs in the US, from 2007 to 2017.

Participants:
All patients receiving one or more classes of diabetes therapies.

Outcomes:
Inflation-adjusted total national expenditures on all diabetes therapies.

Results:
There were substantial increases in total expenditures on diabetes therapies for all payers during the study period, ranging from +165.6% for VA & TRICARE ($380.6 million to $1.0 billion) to +460.4% for Medicaid ($1.1 to $6.1 billion). Private insurers increased spending by +346.6% ($5.7 to $25.5 billion), and Medicare increased spending by +389.9% ($5.4 to $25.2 billion). Out-of-pocket spending increased more modestly (+15.7%, from $4.7 to $5.7 billion).

Conclusions/Relevance:
Spending on diabetes therapies increased dramatically between 2007-2017, with Medicare spending increasing by 389.9%. In contrast, increases in out-of-pocket costs have been more modest. Reasons for the rapid rate of rise in Medicare and private spending compared to out-of-pocket spending should be examined in future studies.
Abstract 14171: Association of Women Authors With Women Enrollment in the Clinical Trials of Atrial Fibrillation
Authors: Khan Safi U , KHAN Muhammad Z , Lone Ahmad N , Subramanian Chraumathi Raghu , Talluri Swapna , HAN JANET K , Isakadze Nino , Volgman Annabelle , Michos Erin D
Published: November 2020

Introduction:
Women with atrial fibrillation (AF) are more symptomatic, have poorer quality of life and carry a higher risk of stroke than men. Despite this woman have been underrepresented in randomized controlled trials (RCTs) of AF.

Hypothesis:
Women representation in the author panel might influence enrollment of women in RCTs of AF.

Methods:
We performed a systematic literature search from 1989 through December 2019 to identify RCTs of AF with a follow-up duration of ≥3 months. The multivariate linear regression model was constructed with the proportion of women enrollment in the RCTs as the dependent variable and the proportion of women in the author panel as a key independent variable. The model was adjusted for publication year, region, sponsor, and type of RCTs (invasive or medical treatment).

Results:
A total of 134 RCTs (n=149,162) were included. The median number of participants per trial was 205 (IQR, 74-676). The median number of women per trial was 71 (IQR, 27-218). The overall representation of women was 35.1% (95% CI, 32.6-37.6%), which did not improve between 1989 to 2019 (from 27.3% to 29.6%; P=0.10). RCTs of AF were authored by 1,568 authors. The median number of authors per trial publication was 10 (IQR, 7-10). The median number of women authors was 1 (IQR, 0-3). First (93%) and senior (92%) authors were predominantly men. Only 13.3% (n=18) of publications had women as first or senior authors, which did not improve over time (P=0.07). Multivariate model showed that each 1% increase in women in the author panel was associated with 19% increase in women enrollment in RCTs (P=0.02) (Table).

Conclusions:
Women remained underrepresented both as participants and as authors of RCTs of AF. Higher representation of women in the author panel was associated with higher enrollment of women in RCTs of AF. Efforts to recruitment and retain women AF investigators may be a critical mechanism to help lessen the disparities in both areas.
Abstract 14182: Genome Wide Association Study for High Sensitive Cardiac Troponin T Levels Identifies a Novel Gene in Europeans With Type 1 Diabetes
Authors: Ahluwalia Tarunveer S , Persson Frederik , Hansen Tine W , Tarnow Lise , Parving Hans-Henrik , Rossing Peter
Published: November 2020

Introduction:
Adults with diabetes have a two to four folds increased risk of dying with heart disease compared to those without diabetes. Higher cardiac troponins, especially Troponin T (TnT) is a specific biomarker for cardiac injury also guiding management of chest pain and associated with increased risk of heart failure.

Hypothesis:
There is limited knowledge on genes regulating cardiac TnT levels. We conducted a genome wide association study (GWAS) for circulating cardiac TnT levels among individuals with type 1 diabetes (T1D).

Methods:
The study included 849 T1D individuals recruited from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Serum high sensitive TnT (hsTnT) levels were measured and log transformed for normalization after check for outliers (mean ± 4 SD). Genotyping on 538,448 single nucleotide variants (SNVs) was done using Illumina Human Core Exome Chip. After quality control filters: hardy weinberg equilibrium (p >10
-6
), European ancestry, genotype call rates >95%, common variants were examined in 740 individuals with hs TnT data. We ran linear regression based additive genetic models adjusting for age, sex, diabetes duration and population sub structure using Plink and R statistical programs. P <5 x 10
-8
was genome wide significant (GWS) while 5 x 10
-8
< p < 1 x 10
-6
was considered suggestive.

Results:
Participants had a mean (SD) age of 43.7 (11.1) years, 57.4% were men, with diabetes duration of 28.0 (9.5) years, HbA1c 8.9 (1.3) % and 50.5% with diabetic nephropathy. Median (IQR) hsTnT levels were 64.7 (29.2-175.6) pg/ml. We identified a GWS missense common variant in the
CISD3
gene locus on chromosome 17 (p=1.7 x 10
-8
) for cardiac hsTnT levels. This gene codes CDGSH Iron Sulfur Domain 3 protein also called Mitochondrial Inner NEET Protein. Two suggestive loci were
PTPRD
(Protein Tyrosine Phosphatase Receptor Type D; p=4.9 x 10
-7
) and
DCC
(DCC Netrin 1 Receptor; 6.6 x 10
-7
) on chromosomes 9 and 18.
PTPRD
is a known GWS locus for hsTnT that we reconfirm among T1D individuals.

Conclusions:
We identify a novel gene locus for circulating cardiac hsTnT levels among T1D individuals of European ancestry. CISD3 is expressed in heart tissue regulating mitochondrial functions. Further validation is suggested.
Abstract 14192: Breakfast Consumption is Associated With Weight Loss During an Intensive Lifestyle Intervention for Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Look AHEAD Trial
Authors: Duan Daisy , Pilla Scott J , Clark Jeanne M , Maruthur Nisa M
Published: November 2020

Background:
Breakfast skipping is linked to obesity and related cardiometabolic outcomes in observational studies, but the association between breakfast eating and weight loss is not well-established. We examined if weight loss outcomes in Look AHEAD were related to breakfast consumption frequency (BCF).

Methods:
We included a subset of participants (n=3862) from the public access dataset of Look AHEAD, an RCT that compared intensive lifestyle intervention (ILI) to diabetes support and education (DSE) control in adults with overweight/obesity and type 2 diabetes. A self-reported questionnaire collected BCF over a 7-day week annually. This value (0-7) was averaged across 4 years of the intervention to calculate an average BCF. We used robust multivariable linear regression analysis to estimate the association between % weight change and 4-year average BCF controlling for baseline sociodemographics, BMI, and diabetes-related variables. In separate models, we adjusted for self-reported caloric intake (n=880) and self-reported physical activity level (n=735) among those with data.

Results:
4-year average BCF was similar in DSE (n=1914) and ILI (n=1948) arms, with a median of 7 days (IQR 6-7) for both arms (p=0.11). Each 1 day increase in average BCF was associated with an additional 0.43% weight loss in the ILI arm (p=0.002) but not in the DSE arm (β-coefficient 0.04% weight loss; p=0.73; p-interaction for arm x BCF=0.01). This association in the ILI arm remained significant after adjustment for daily caloric intake (p=0.04) but not after adjustment for physical activity (p=0.16).

Conclusions:
Breakfast consumption was associated with greater weight loss in subjects who received ILI, which was attenuated after adjustment for caloric intake and physical activity. To optimize weight loss interventions, the relationship between breakfast consumption and other weight loss behaviors should be further explored.
Abstract 14194: Triple Vessel Spontaneous Coronary Artery Dissection With Coronary Artery Fibromuscular Dysplasia
Authors: Schweis Franz , Rostomian Ara , Phan Derek , Lee Mingsum , Ichiuji Anne , Shen Albert Yuh-Jer , Moore Naing
Published: November 2020

Introduction:
Spontaneous coronary artery dissection (SCAD) is a rare albeit well-established etiology of myocardial infarction and most commonly involves a single coronary vessel. We present a unique case of a patient presenting with chest pain and found to have triple vessel SCAD with associated findings suggestive of coronary artery fibromuscular dysplasia (FMD).

Case Presentation:
A 53 year-old woman with a past medical history of hypertension and chronic headaches presented with intermittent exertional substernal chest pain for two days. Labs were significant for an elevated Troponin-I of 0.12 ng/mL (normal < 0.04 ng/mL). Coronary angiogram revealed tortuous vessels with evidence of SCAD in multiple coronary arteries including the left anterior descending artery (LAD), posterior descending artery (PDA), and posterior left ventricular artery (PLV) (Figure A, B). Intracoronary nitroglycerin was administered during the procedure to ensure the findings were not due to coronary vasospasm. Due to the known association of SCAD and FMD, a renal angiogram was performed, which demonstrated a “beading” appearance of the right renal artery consistent with renal artery FMD. She was conservatively managed with medical therapy.A head computed tomography angiogram (CTA) was performed, which showed evidence of FMD of the bilateral vertebral arteries. A repeat coronary angiogram was performed six weeks after discharge. She was found to have complete resolution of SCAD in the LAD and PLV

(Figure C, D). Interestingly, the PDA displayed a “string of beads” appearance concerning for intracoronary artery FMD (Figure D).

Conclusion:
Our case demonstrates evidence that coronary artery FMD may contribute to the underlying etiology of the coronary artery dissection. A conservative management approach resulted in a favorable outcome and the patient was able to avoid unnecessary intervention and potential related complications.
Abstract 14199: Long-term Impact of Baseline Anemia and Dual Antiplatelet Therapy Duration After Percutaneous Coronary Intervention
Authors: Kim Huntae , Park Jong-Il , Kim Byung-Jun , Lee Jung-hee , Kim Ung , Park Jong-Seon
Published: November 2020

Background:
Anemia is a known risk factor for future ischemic events and bleeding for patients with ischemic heart disease. However, there are little data about dual antiplatelet therapy (DAPT) duration for patients with anemia after percutaneous coronary intervention (PCI).

Methods:
From 2010 to 2013, a total of 1,470 patients who underwent PCI were investigated. We categorized the study population into four groups based on the DAPT duration and anemia (Hemoglobin <13g/dL for men and <12g/dL for women): Group A (non-anemia & ≤12m DAPT, n=521), Group B (non-anemia & >12m DAPT, n=501), Group C (anemia & ≤12m DAPT, n=226), and Group D (anemia & >12m DAPT, n=222). We evaluated major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction, repeat target vessel revascularization, or stroke, and bleeding complication.

Results:
Even though anemic patients had more severe angiographic findings, such as three-vessel disease or diffuse long lesion, the DAPT duration was similar between anemia and non-anemia group. MACCEs occurred less frequently in Group B (16.9%) than Group A (24.7%), Group C (34.6%), and Group D (35.1%) (p<0.001) at 8 years. After multivariate analysis, with Group A as a reference, the adjusted hazard ratio for MACCEs was 0.711 (95% confidence interval [CI] 0.526-0.961, p=0.027) for Group B, 1.126 (95% CI 0.802-1.581, p=0.494) for Group C, and 0.995 (95% CI 0.706-1.405, p=0.980) for Group D. However, major bleeding occurred more frequently occurred in Group D (13.0%) than Group A (5.7%), Group B (7.5%), and Group C (11.2%) (p=0.035) at 8 years.

Conclusions:
Although extended DAPT showed reduced rate of MACCEs for non-anemic patients, it can be related with increased of major bleeding for anemic patients.