bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17882: A Method for Real-time CPR Detection From the Thoracic Impedance Signal
Authors: Kwok Heemun , Coult Jason , Sherman Lawrence , Blackwood Jennifer , Kudenchuk Peter , Rea Thomas
Published: March 2022

Introduction:
Accurate detection of chest compressions is a means to improve CPR through real-time feedback or post-event review. Accelerometer technology is the gold standard to detect compressions but is not universally available and requires additional equipment.

Hypothesis:
An algorithm derived from the transthoracic impedance signal could achieve high sensitivity and specificity for compression detection and accurately measure the CPR fraction.

Methods:
Defibrillator recordings from cardiac arrest cases were used to develop (N=20) and validate (N=62) the compression detection algorithm. Accelerometer data were used to define the presence or absence of compressions at 1-second intervals throughout entire cases, up to 10 minutes per case. The impedance-based algorithm cross-correlates the impedance signal with a series of wavelets and then integrates sequential outputs with a hidden Markov model. Using accelerometer classification as the gold standard, the sensitivity and specificity of the impedance-based algorithm for compression detection were estimated by a multilevel model to account for clustering of classifications within cases. The difference in CPR fractions was calculated for each case by subtracting the accelerometer-derived CPR fraction from the impedance-derived CPR fraction, and their median and 95% CI were estimated by the Wilcoxon signed-rank test.

Results:
The validation set included a median 535 seconds per case. The impedance-derived algorithm had mean sensitivity 0.95 (95% CI 0.93, 0.96) and mean specificity 0.91 (95% CI 0.90, 0.93). Median CPR fraction was 0.74 (IQR 0.65, 0.79) based on the accelerometer assessment. The impedance-derived CPR fraction was 0.71 (95% CI 0.64, 0.77), for a difference of -0.01 (95% CI -0.03, 0.00).

Conclusion:
A method that identifies CPR from the impedance signal alone had high mean sensitivity and high mean specificity but slightly underestimated the CPR fraction.
Abstract 17946: How Common is New Onset Atrial Fibrillation in Single Chamber ICD Patients? Sub-analysis From the PainFree SST Study
Authors: Schloss Edward J , Auricchio Angelo , Kurita Takashi , Meijer Albert , Rogers Tyson , Tejima Tomoyuki , Brown Mark L , Sterns Laurence D
Published: March 2022

Introduction:
Nearly 75% of ICD recipients have no history of atrial fibrillation (AF) at the time of initial implantation. Yet, many of these patients will develop new onset AF after implant which can lead to serious consequences if not detected and treated. To date, detection algorithms in single-chamber ICDs are not able to detect AF. We investigate how common is new onset AF in single chamber (SC) ICD recipients compared to CRT-D and dual chamber (DC) ICD recipients.

Methods:
A total of 924 patients with no history of AF from the PainFree SST study (CRT-D: N=321, DC ICD: N=303, SC ICD: N=300) were investigated. We used data from dual-chamber ICDs to estimate the incidence of new-onset AT/AF in SC ICD patients. A propensity score weighted analysis was performed using DC ICD data to match the baseline data of SC ICD patients. Patients with pacing indication were excluded from this evaluation because they would not be indicated for SC ICD. AT/AF-related complications include AT/AF-related serious adverse events, thromboembolic events, progress to AF lasting 7 days or more as well as inappropriate shocks due to AT/AF. Simulated SC ICD results were compared to actual DC and CRT-D results.

Results:
For AF episodes lasting 6 minutes or more, the incidence rates in CRT-D, DC ICD, and the estimated SC ICD were 28.0%, 23.4%, and 20.5% at 24 months, respectively (Table). The estimated incidence rates of AT/AF episodes in patients with SC ICD were comparable to those of DC ICD in each episode duration. Once the patients experienced first AT/AF episode, the complications were common (Table).

Conclusions:
AT/AF was frequently detected following implant in patients with no AF history receiving ICD or CRT-D and is associated subsequent AT/AF-related complications even in SC ICD recipients. Therefore, AT/AF monitoring in all ICDs patients may identify those at risk for these complications.
Abstract 17961: Circulating MicroRNA-122 is Associated With Incident Metabolic Syndrome and Type-2-diabetes
Authors: Willeit Peter , Yin Xiaoke , Kaudewitz Dorothee , Skroblin Philipp , Zampetaki Anna , Moschen Alexander R , Ramirez Cristina M , Goedeke Leigh , Rotllan Noemi , Bonora Enzo , Hughes Alun D , Weger Siegfried , Fernandez-Hernando Carlos , Tilg Herbert , Willeit Johann , Kiechl Stefan , Mayr Manuel
Published: March 2022

Background:
MicroRNA-122 (miR-122) is highly abundant in the liver and has been implicated in lipid and glucose homeostasis.

Methods:
Circulating miR-122 levels were measured in the prospective population-based Bruneck Study (n=810) and the ASCOT trial (n=155 pre/post atorvastatin initiation). Using mass spectrometry, we measured 135 lipid subspecies and 93 plasma proteins in Bruneck participants. We also conducted mechanistic studies in pre-clinical models and cultured hepatocytes. We calculated risk ratios over up to 15 years follow-up for cardiometabolic diseases using pooled logistic and Cox regression, incorporating repeated miR-122 measurements.

Results:
In the Bruneck Study, miR-122 was associated with an adverse metabolic profile, including insulin resistance, obesity, and prevalent metabolic syndrome and diabetes. MiR-122 positively correlated with lipid subspecies containing fatty acids that can be derived from hepatic de novo lipogenesis. In mice, miR-122 inhibition with antagomiR treatment down-regulated hepatic enzymes implicated in de novo lipogenesis and cholesterol synthesis. In the ASCOT trial, 10mg atorvastatin treatment led to a reduction in circulating miR-122 levels. A similar statin response was observed in mice and in primary hepatocytes. In the Bruneck Study, miR-122 was closely related to circulating levels of afamin, zinc-alpha-2-glycoprotein, and a wide range of apolipoproteins. The adjusted relative risk per SD higher log miR-122 was 1.60 (1.30-1.96; P<0.001) for metabolic syndrome, 1.37 (1.03-1.82; P=0.021) for type-2 diabetes, and 1.10 (0.90-1.33; P=0.330) for cardiovascular disease. Risk ratios were similar upon further adjustment, for women and men, and by clinical categories of adiposity.

Conclusion:
This study provides strong evidence for an involvement of miR-122 in glucose and lipid metabolism. High miR-122 levels correlate with an adverse lipid profile and multiple metabolic abnormalities and are associated with a higher risk of new-onset metabolic syndrome and diabetes in the general community.
Abstract 17973: Clinical Markers Associated With Subclinical Atherosclerosis in Otherwise Apparently Healthy Young Adults
Authors: LeBlanc Stephanie , Bibeau Karine , De Larochellière Élianne , Pibarot Philippe , Després Jean-Pierre , Larose Eric
Published: March 2022

Introduction:
Traditional risk factors are poor predictors of cardiovascular events in younger adults. Considering the long silent evolution of atherosclerosis beginning in younger adulthood before the appearance of clinical events at a more advanced age, a simple tool to predict early atherosclerosis in young adults would be desirable to guide primordial prevention. An altered cardiometabolic profile is associated with increased cardiovascular disease in older adults independent from traditional risk factors, but the value of this profile in an otherwise healthy young adult population is unknown.

Hypothesis:
Cardiometabolic risk markers would be associated with early atherosclerosis in young adults despite the absence of traditional risk factors.

Methods:
Healthy young adults (18-35 years) devoid of cardiovascular risk factors (diabetes, smoking, hypertension, dyslipidemia) and obesity were prospectively enrolled. Anthropometric measurements, ECG, lipid profile, fasting blood glucose, blood pressure and high-resolution carotid artery MRI were realized.

Results:
Although the 240 participants (25.8 years, SEM=0.29, 48% women) were at low risk for atherosclerosis, we identified atherosclerosis in 72.6% of men and 64.7% of women (p=0.19). Males had greater atherosclerosis burden vs. females (carotid wall volume [CWV]: 1817 mm3/48mm, SEM=29.7 vs. 1579 mm3/48mm, SEM=21.2; p<0.0001). By multivariate analysis, atherosclerosis burden was associated with fasting blood glucose (p=0.01), BMI (p=0.01), and waist circumference (p<0.001), the latter having the strongest correlation with atherosclerosis burden (r=0.41, p<0.0001). ROC analyses established cutoffs for waist circumference identifying greater atherosclerosis burden in apparently healthy young adults.

Conclusion:
A simple low-cost office-based tool, waist circumference measurement improves prediction of early atherosclerosis in otherwise apparently healthy young adults.
Abstract 17978: Mlp Interacting Protein 1 (MIP1) Plays a Role for Cardiomyopathy
Authors: Buyandelger Byambajav , Mansfield Catherine , Kostin Sawa , Choi Onjee , Isaacson Rivka L. , Poon Kar-Lai , Knöll Gudrun , McSweeney Sara , Perrot Andreas , Toliat Mohammad R , Chen Ju , Gould Ian , Lara-Pezzi Enrique , Luther Pradeep , Petretto Enrico , Milting Hendrik , Brand Thomas , Knöll Ralph
Published: March 2022

Mutations in genes involved in cardiac mechanosensation (mec), such as the muscle LIM protein (MLP) have been shown to cause heart failure. Identification of novel mec genes may provide new insights into underlying mechanisms.

A yeast 2 hybrid screen identified a novel MIP, located at a chromosomal region recently implicated by GWASs in the pathogenesis of dilated cardiomyopathy (DCM), an interaction confirmed by various assays.

We found that MIP1 is a stress inducible transcription factor, binds to the calcineurin promoter and activates NFAT, a known mediator of hypertrophy. Also overexpression of MIP1 in vitro promotes autophagy and activates expression of anti-apoptotic genes in cardiac myocytes.

Mip1 conventional knockout animals die during gastrulation whereas Mip1 conditional knockout (cKO) animals failed to adapt to transverse aortic constriction. Four weeks after intervention, fractional shortening was significantly decreased, whereas LVEDD and LVESD were significantly increased in cKO mice compared to control littermates.

TUNEL assays combined with activated caspase, whole gene expression arrays and qRT-PCR provide strong evidence that Mip1 cKO hearts are unable to undergo autophagy and as a result activate apoptotic processes which are responsible for the observed heart failure phenotype. However, overexpression of MIP1 in vivo resulted in marked cardiac hypertrophy at the organ and single cell levels, pointing to a link between autophagy and hypertrophy.

As MIP1 contains the peak association signal (rs10927875) at the replicated 1p36 cardiomyopathy locus, we sequenced this gene in 575 unrelated individuals affected by DCM and identified 4 MIP1 missense mutations (T106M, G179S, A188V, Q531R) of which 2 co-segregate in two families with DCM and arrhythmia. All 4 variants show abnormalities with regards to their ability to interact with MLP, localization, structure, stability and potential to drive the calcineurin promoter. WT-MIP1 is able to efficiently protect cells from apoptosis, a property missing in all mutants. At least G179S and Q531R cause heart failure in the zebrafish.

MIP1 is important for the initiation of survival pathways and autophagy upon biomechanical stress and represents a novel cardiomyopathy candidate gene.
Abstract 18006: Functional Effects of a Missense Common Variant in Neuregulin-1 Associated With Low Ejection Fraction and Sudden Cardiac Death
Authors: Huertas-Vazquez Adriana , Xu Bing , Reinier Kyndaron , Teodorescu Carmen , Uy-Evanado Audrey , Narayanan Kumar , Gunson Karen , Jui Jonathan , Hong TingTing , Shaw Robin M , Chugh Sumeet S
Published: March 2022

Objective:
To investigate the functional effects and genotype-phenotype correlation of a coding variant within the Neuregulin-1 gene (NRG1), which we previously identified from a community-based study of sudden cardiac death (SCD).

Methods:
The Missense variant Met286Thr within NRG1 was characterized by transfecting NRG1 wild type and mutant in HEK293 cells with a tag placed on the extracellular domain for assessment of membrane expression. To study genotype-phenotype correlations, we performed a case-case analysis comparing SCD carrier cases of the risk allele (n=384) vs. non SCD carrier cases (n=888). A total of 1,272 SCD cases of European descent were included in the study. Regression models adjusted for age and sex were tested to evaluate the correlation of the risk allele and clinical variables obtained ECGs and Echocardiograms of SCD cases.

Results:
We found that, unlike wild type NRG1, the Met286Thr variant did not traffic to the cell membrane (Figure), indicating defects in antegrade protein transport. We also found that in the subset of SCD cases with echocardiograms available (n=253), carriers of the risk allele were more likely to present with low ejection fraction (LVEF ≤35%) compared with the non-carrier cases (P=0.02, OR= 2.26 [1.14-4.5]. Other investigated risk factors such as QT prolongation, QRS duration, heart rate, left ventricular hypertrophy and coronary artery disease were not significantly different (P>0.05).

Conclusions:
We have identified a novel variant in the transmembrane domain of NRG1, which results in defective antegrade transport and is associated with SCD and low ejection fraction. These findings support a role for Met286Thr in trafficking pathways leading to both functional compromise and ventricular arrhythmogenesis.
Abstract 18015: “Apical Sparing” Longitudinal Strain Pattern With Cardiac MRI Correlates With LGE Distribution in Cardiac Amyloidosis
Authors: Williams Lynne K , Forero Julian , Calleja Anna , Delgado Diego , Crean Andrew M , Rakowski Harry , Thavendiranathan Paaladinesh
Published: March 2022

Introduction:
Regional variations in longitudinal strain (LS) have been demonstrated on echocardiography in patients with cardiac amyloidosis (CA).

Hypothesis:
We aimed to describe regional patterns in LS using feature-tracking software applied to cardiac MRI images (CMR) in CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry’s disease (AFD) and to relate these patterns to late gadolinium enhancement (LGE).

Methods:
Patients with CA (n=51) were compared to left ventricular mass index balanced patients with HCM (n=20) and AFD (n=20). LS analysis was performed using Velocity Vector Imaging (VVI) on steady state free precession cine images (4, 3, and 2-chamber views). Values were recorded for each of 18 myocardial segments. A regional LS ratio representing “apical sparing” was calculated as the ratio of the sum of the apical segmental LS values divided by the sum of the basal and mid-segmental LS values. LGE was quantified for the basal, mid, and apical myocardial segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to the “apical sparing” ratio.

Results:
The regional LS ratio was significantly higher in patients with CA (1.05±0.49) than in patients with AFD (0.79±0.24; p=0.025) and HCM (0.84±0.32; p=0.025). In patients with CA there was a regional difference in LGE burden, with lower LGE in the apex (31.9±20%) compared to the basal (52.7±22%) and mid-segments (37.9±19%). The regional LGE ratio was significantly lower in patients with CA (0.34±0.14) than in patients with AFD (0.54±0.64; p<0.001) and HCM (0.73±0.41; p<0.001).

Conclusions:
Cardiac amyloidosis is characterized by regional variations in LS from base to apex. “Apical sparing” in LS is seen with CMR images and can be an additional tool to differentiate CA from other causes of LVH. The concomitant presence of a base to apex gradient in LGE burden by CMR suggests that the regional strain gradient may be associated with burden of amyloid deposition.
Abstract 18016: Cell and Hydrogel-based Therapies Employing Cathelicidin Related Antimicrobial Peptide (CRAMP) Attenuate Cardiac Dysfunction in a Mouse Model of Myocardial Infarction: Potential Therapeutic Targets in Ischemic Heart Disease
Authors: Klyachkin Yuri M , Ye Shaojing , Nagareddy Prabhakara , Asfour Ahmed , Annabathula Rahul , Smyth Susan S , Abdel-Latif Ahmed
Published: March 2022

Introduction:
Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Cathelicidins related antimicrobial proteins (CRAMPs) have been shown to prime bone marrow Derived mononuclear Cells (BMMNC) migration towards low gradients of SDF-1 suggesting a potential role in BMMNC retention. Here, we assessed the therapeutic efficacy of CRAMP in the context of BMMNC recruitment and retention via intracardiac delivery of CRAMP-treated BMMNCs or CRAMP-packed hydrogels (HG) post-myocardial infarction (MI).

Methods and Results:
During the in vivo cell studies, mice were randomized into 3 groups: MI followed by injection of PBS, BMMNCs alone, and BMMNCs incubated with CRAMP. During the in vivo HG studies, BM GFP chimera mice were randomized into 4 groups: MI followed by injection of HG alone, HG + SDF-1, HG + SDF-1 + CRAMP, HG + CRAMP. Changes in infarct size and cardiac function between 5 days and 5 weeks after MI were assessed using cardiac MRI (CMR) and echocardiography respectively. Treatment of BMMNCs with CRAMP enhanced their migration towards low, yet physiological, levels of SDF-1 in vitro (Fig 1A). In vivo, BMMNC+CRAMP therapy was associated with significant increase in capillary density as compared to the BMMNC-alone and control groups (Fig 1B). Moreover, BMMNC+CRAMP administration led to improvement in cardiac function and reduction in infarct size as compared to other groups (Fig 1C-D). Similar to the BMMNCs+CRAMP cell therapy, HG + SDF-1 + CRAMP administration post-MI led to improvement of cardiac function and reduction in infarct size compared with other groups (Fig 1E-F).

Conclusion:
Cathelicidins enhance BMMNC retention and recruitment after intramyocardial administration post-MI resulting in improvements in heart physiology and recovery. Therapies employing these strategies may represent an attractive method for improving outcomes of regenerative therapies in human studies.
Abstract 18049: Improved Survival in Out of Hospital Cardiac Arrest: Withholding Positive Pressure Ventilation
Authors: Scheppke Kenneth , Ippolito James , Breyer Keith , Chait Robert
Published: March 2022

Hypothesis:
The withholding/delay of positive pressure ventilation can improve out of hospital adult primary cardiac arrest survival.

Methods:
All adult primary cardiac arrest victims in a single municipal (Sate of Florida) Fire/Rescue service in whom resuscitation attempts were made were initially given chest compressions only. Positive pressure ventilation was withheld until the first of either 10 minutes or return of spontaneous circulation (ROSC). Continuous uninterrupted chest compressions were an integral part of the protocol. Primary cardiac arrest was defined as an arrest not felt to be due to hypoxia. The Florida State EMSTARS (EMS Tracking and Reporting System) database provided the information for statewide average ROSC.

Results:
Over a two-year period the ROSC and neurologically intact recovery rate was dramatically improved over Florida State average controls. The 2013 total ROSC rate was 40% (18/45) compared to a Florida State average ROSC of 16.7%. The 2014 primary cardiac arrest ROSC rate was 51.5% (17/33) with 29.4% of the ROSC patients or 15.2% of the total achieving neurologically intact survival. This compares to the 2014 Florida State average ROSC of 17.9%.

Conclusion:
Delayed positive pressure ventilation seems to be associated with both improved ROSC and neurologically intact survival in adult out of hospital primary cardiac arrest. Further study is warranted to determine the extent of this association.
Abstract 18051: Mechanical Circulatory Support and Pulmonary Hypertension - An Analysis of United Network of Organ Sharing Registry
Authors: Zalawadiya Sandip , Egolum Ugochukwu , Ooi Henry
Published: March 2022

Background:
Severe pulmonary hypertension (PH) is a relative contra-indication for heart transplantation (HT) per International Society of Heart and Lung Transplantation guidelines. Limited data exists comparing different types of mechanical circulatory support devices (MCSDs) for post-HT survival across severity categories of PH.

Methods:
We performed post-hoc analysis of 14,481 patients (age: 53.3± 12 years, 76% males, median follow-up - 4.2 years) undergoing HT after January 1st, 2000 from the United Network of Organ Sharing registry database. Patients were divided into following categories of PH: None (pulmonary vascular resistance (PVR) <2.5 WU or trans-pulmonary gradient (TPG) <13 mmHg), mild to moderate (PVR ≥2.5 WU and <5 WU or TPG≥ 13 mm Hg and <20 mm Hg) and severe (PVR ≥ 5.0 WU or TPG ≥ 20 mm Hg). We also categorized patients based on types of MCSDs as following: None (n=10,142), pulsatile flow (PF) left (n=709), continuous flow (CF) left (n=3,166), biventricular (BiV; n=347) and total artificial heart (TAH;n=117). Post-HT survival was assessed using multivariable Cox proportional hazard analysis across categories of PH and MCSDs.

Results:
See Figure 1 and 2.

Conclusion:
For patients without PH, CF left MCSDs offered significantly better post-HT survival compared to other categories of MCSDs; risk of post-transplant mortality among those with PH was comparable between CF left MCSDs and those undergoing direct HT or having PF left MCSDs.
Abstract 18094: Appalachian Youth and Tobacco Products: Perceptions, Attitudes, and Behaviors
Authors: Hart Joy L , Sears Clara , Lee Alexander , Smith Courteney , Siu Allison , Walker Kandi L
Published: March 2022

Crucial to ending the scourge of tobacco addiction is reducing youth use of the various products. Despite reduction in youth cigarette use, other products (e.g., hookah, e-cigs) have increased in popularity in this age group (CDC, 2013, 2015). Use patterns are also influenced by factors such as social acceptance, peer use, SES, and accessibility (US DHHS, 2012, 2015). Some areas have higher youth tobacco use rates (Kruger et al., 2012; US DHHS, 2012, 2015); for example, use of tobacco by middle and high school students in Appalachia continues to exceed rates in other areas. Increased understanding of the factors promoting this use is vital to developing effective youth anti-tobacco campaigns and public policy.

Objective:
To assess Appalachian middle and high school students’ perceptions of, attitudes about, and use of tobacco products.

Methods:
Data were collected in three Appalachian states: Kentucky, New York, and North Carolina. These states were selected for differences in overall use of tobacco by youth (i.e., Kentucky: high, North Carolina: mid-level, New York: low). From October 2014-May 2015, 23 focus groups were conducted with middle and high school students (N=203). Each participant completed a questionnaire on perceptions of and attitudes about tobacco, use of tobacco, and views of health consequences and engaged in an open-ended focus group discussion.

Results:
Traditional tobacco products continue to be popular with Appalachian youth. For example, 29% of the participants have tried at least one tobacco product, with significant numbers of daily users (9% smokeless tobacco; 6% cigarettes). E-cig use was nearly as high, with approximately 22% reporting some experience. Findings also revealed varying attitudes and discrepant conclusions surrounding e-cigs. Comparisons between tobacco users and nonusers as well as by middle and high school status and state will be addressed.
Abstract 18100: Community-Based, Targeted CPR Education to Improve Survival From Out-of-hospital Cardiac Arrest in Tampa’s High-risk Neighborhoods
Authors: Waxler Jennifer , Panchal Ashish , Rivera Ronnie , Del Rios Marina , Revette Nacole , Magazin Maja , Hogue Deanna , Heard Debra , Sasson Comilla
Published: March 2022

Introduction:
The Hands-Only CPR™ Program is a novel intervention designed to target high-risk neighborhoods (where the incidence of cardiac arrest is high and bystander CPR rates are low) to increase CPR performance. The program has been successfully implemented in pilot projects, however, the feasibility of implementing this program in additional communities is unknown.

Objective:
Conduct a feasibility study of a community-based Hands-Only CPR program in Tampa’s high-risk neighborhoods.

Methods:
Population: Convenience sample of 740 participants were recruited from target neighborhoods during a 16-week study period. Intervention: Participants completed a pre-test survey to for baseline CPR knowledge followed by a group Hands-Only CPR training (1 hour) conducted with the CPR Anytime kit, which includes an educational DVD and hands-on practical skills training with a manikin. Participants then completed a survey to assess their post-training knowledge and were asked to use the kits to train others. A $10 gift card incentive was given to participants once follow-up information was returned.

Results:
Participants were a mean age of 46.6 years, White (41.9%), Hispanic/Latino (37.6%), female (67.7%), had completed high school or above (82.6%), and had an annual income of less than $30,000 (35.8%) (Table 1). After the CPR intervention, the mean number of questions answered correctly on CPR knowledge increased. The majority of participants (81.1%) felt comfortable performing Hands-Only CPR after the intervention. 580 completed the pre- and post-tests. Of these 580, 37 (6.4%) participants returned information, with an additional 137 friends and family trained.

Conclusion:
The Hands-Only CPR Program is a novel method to increase the knowledge of CPR and comfort performing CPR in a target population. Additional studies will need to be conducted to test this intervention in other communities as well as its overall effect on bystander CPR rates.
Abstract 18102: Threshold Effect of Vitamin D Deficiency on Cardiovascular Outcomes: Below What Level of 25(OH) Vitamin D is Cardiovascular Risk Really Increased?
Authors: Muhlestein Joseph B , Bair Tami L , May Heidi T , Le Viet T , Lappé Donald L , Anderson Jeffrey L
Published: March 2022

Introduction:
Epidemiologic studies have identified low 25(OH) vitamin D (vitD) levels as an independent risk factor for cardiovascular (CV) disease and total mortality. However, the actual vitD level threshold below which cardiovascular risk increases is not clearly established.

Hypothesis:
Among a large general population of patients undergoing clinical testing for vitD, a specific threshold level below which CV risk rises can be identified.

Methods:
All patients in the Intermountain Healthcare clinical database with at least one vitD level and no history of heart or renal failure were identified. Baseline vitD levels were stratified into four groups (<15 ng/mL [9.2%], 15-29 ng/mL [45.3%), 30-44 ng/mL [32.6%], ≥45 ng/mL [12.8%]) and followed for up to 3 (n=140,056) or 5 (n=69,887) years for MACE including death, new diagnosis of coronary artery disease (CAD), myocardial infarction (MI), stroke and incident heart (HF) or renal (RF) failure. Five year MACE hazard ratios (HRs) comparing groups were calculated by Cox regression, adjusting for 17 baseline variables.

Results:
A total of 234,920 patients (age 48±20 y, female: 72%, diabetes: 12%, hypertension: 29%, hyperlipidemia: 30%) were studied. Event rates at 3 and 5-y by vitD group are shown in the Table. Adjusted 5 yr MACE HRs, using vitD<15 ng/mL as the comparator, were HR=0.80(p<0.0001), HR=0.75(P<0.0001) and HR=0.75(p<0.0001) for vitD ≥45 ng/mL, 30-44 ng/mL and 15-29 ng/mL respectively, and using vitD≥45 ng/mL as the comparator, were HR=1.34(p<0.0001), 1.07(p=0.02) and 1.00(p=0.93) for vitD<15 ng/mL, 15-29 ng/mL and 30-44 ng/mL respectively.

Conclusions:
Among a large general population undergoing clinical testing for vitD, a 35% increased CV risk was identified, and was limited to only those with vitD levels <15 ng/mL, comprising 9.2% of the entire group. It is therefore likely that any clinical cardiovascular benefits from vitD supplementation will be limited to those with the lowest baseline vitD levels.
Abstract 18103: Community Trends in Incidence and Mortality of Hospitalized Acute Decompensated Heart Failure: The ARIC Study
Authors: Chang Patricia P , Wruck Lisa M , Bessell Marina , Shahar Eyal , Rossi Joseph S , Loehr Laura R , Russell Stuart D , Agarwal Sunil K , Konety Suma H , Rodriguez Carlos J , Rosamond Wayne D
Published: March 2022

Introduction:
Understanding population-based trends in heart failure incidence is important to evaluation and planning of prevention and treatment strategies.

Hypothesis:
Community trends of acute decompensated heart failure (ADHF) in racially diverse populations may differ by race and sex.

Methods:
The Atherosclerosis Risk in Communities (ARIC) Study conducted continuous and comprehensive surveillance of hospitalized ADHF events (age ≥55 years) in four US communities between 2005-2012 and estimated hospitalized ADHF incidence and survival by race and sex. 17,651 hospitalizations for ADHF were identified by ICD-9-CM codes, then validated by standardized physician review of hospital records, yielding a weighted sample of 31,006 hospitalizations after accounting for sampling design. HF with reduced EF (HFrEF) was defined as EF<50%.

Results:
Of the ADHF hospitalizations, 16259 (52.4%) were HFrEF, 11835 (38.2%) were HF with preserved EF (HFpEF), and 2912 (9.4%) were HF with unknown EF. HFrEF (both incident and recurrent ADHF) was more common in men (black men 70.4%, white men 61.4%), whereas HFpEF was more common in women (white women 50.0%, black women 39.5%). Compared to whites, blacks were younger, with less coronary heart disease and atrial arrhythmias, and more hypertension, diabetes, and chronic kidney disease. Between 2005-2012, the incidence of hospitalized ADHF increased, which mostly reflected the increase in rates of HFpEF (average annual percent change of incident HFpEF: black women 16.6%, black men 13.2%, white women 8.0%, white men 8.3%), with higher age-adjusted average incident HFpEF rates in women (black women 6.2 per 1000 persons, white women 5.9/1000, black men 4.6/1000, white men 4.2/1000). Changes in HFrEF incidence and changes in 28-day and 1-year case fatality for HFpEF and HFrEF were modest and generally not statistically significant. Age-adjusted 1-year case fatality was similar across all race-sex groups (~30% after any incident ADHF). Similar trends were seen for recurrent ADHF (HFpEF and HFrEF).

Conclusions:
Incident ADHF rates increased between 2005 and 2012 in the ARIC Study communities, primarily because of incident HFpEF in women and blacks. Further study is needed to understand the differences by race and sex.
Abstract 18124: An Irx4+ Ventricular Progenitor Isolated by Spherical Nucleic Acid Nanoparticles
Authors: Biermann Mitch , Shao Annie , Han Tianxiao , Lyons Gary , Kamp Timothy
Published: March 2022

While human pluripotent stem cell-derived cardiomyocytes have shown promise in engrafting and maturing in animals following myocardial infarction, transplanted cells largely exist as histologically self-contained blocks of cells with moderate or undetectable functional benefit. We therefore sought to develop methods to isolate a proliferative progenitor capable of differentiating both to functional ventricular cardiomyocytes and supportive cardiac mesenchymal cells, as these cells may hold promise for regenerative medicine. To isolate a ventricular progenitor, fluorescent spherical DNA nanoparticles (nanoflares) were synthesized to target RNA of the ventricular transcription factor Irx4 at an intermediate stage in cardiac differentiation of human pluripotent stem cells using small molecule, defined conditions without genetic modification or transfection. The synthesized nanoflare was nontoxic by Annexin V/7AAD flow cytometry and did not affect differentiation or expression of cardiac genes in RT-qPCR, including Irx4. Upon differentiation, nanoflare-FACS-separated Irx4+ cells were found to give rise to 50% cTnT+ cardiomyocytes and 46% Thy1+ mesenchymal cells. In sorted cells, we used sensitive droplet digital RT-PCR to detect early upregulation of lineage-specific genes. Relative to Irx4 -/Low cells, Irx4+ cells had significant upregulation of ventricular-specific mlc2v but not atrial genes (Hey1, CoupTF2, SLN). In characterizing their mesenchymal potency, Irx4+ cells had significant enrichment in smooth muscle actin and N-cadherin. Intriguingly, during monolayer differentiation of Irx4+ cells, a marked aggregation occurs in which Thy1+ mesenchymal cells surround and embed large assemblies of beating cTnT+ cardiomyocytes. Consistent with a matrix remodeling phenotype, both protease inbitior expression (TIMP1) and protease activity by zymography were increased in sorted Irx4+ compared to negative cells.

Conclusions:
We have here isolated early ventricular progenitor cells using novel, non-invasive methods. Their remodeling activity may allow more seamless myocardial integration than differentiated cardiomyocytes and provide insights into the role of cell-cell interactions during human cardiac development.
Abstract 18185: Clinical Impact of Left Atrial Appendage Closure on the Incidence of Stroke, Bleeding and on Quality of Life in Patients With Atrial Fibrillation: A Standardized Single Center Registry
Authors: Poerner Tudor C , Wieg Stephanie , Goebel Björn , Otto Sylvia , Figulla Hans R
Published: March 2022

Introduction:
We aimed to assess the impact of left atrial appendage closure (LAAC) on the incidence of cardiac mortality, stroke, bleeding and quality of life (QOL) in a standardized single center registry.

Methods:
At our institution LAAC using the Watchman device has been recommended since 2010 in all patients (pt) with atrial fibrillation (AF) and bleeding events under oral anticoagulation therapy (OAC). Postprocedural antithrombotic therapy included aspirin for life, OAC or low molecular weight heparins (LMWH) for 45 days, followed by clopidogrel up to 6 months after LAAC. In pt with absolute contraindications against OAC, clopidogrel was started after LAAC and given for 6 months without OAC/LMWH. An ambulatory examination with transesophageal echo at 45 days and a standardized clinical follow-up (f/u) at 1 year including QOL assessment using a modified 17-questions AFEQT™ questionnaire were routinely performed.

Results:
Ninety consecutive pt (52 males) aged between 53 - 90 years (74.3 ± 7, median 75) underwent LAAC between 2010 and 2013. The CHA2DS2VASc score ranged between 2 - 6 (4.1 ± 1.1, median 4) and the HAS-BLED score between 2 - 8 (4.4 ± 1.6, median 4). Confirmed history of stroke was present in 11 pt, of whom 9 had a non-chicken wing morphology of the appendage (p < 0.01). Procedural success was obtained in 89 of 90 pt, while 3 pt needed 2 occluders to fully close the LAA. Clinical f/u data and the modified AFEQT™ questionnaire, which was completed by 49 pt are shown in Tables 1 and 2.

Conclusions:
In AF pt with high stroke and bleeding risk LAAC effectively reduced both bleeding complications and ischemic stroke and also significantly improved quality of life at 1-year follow-up.
Abstract 18186: Evaluating the Utility of a Multi-factorial Computational Model and Simplified Multi-factorial Risk Score to Predict Postoperative Atrial Fibrillation Following Cardiothoracic Surgery
Authors: Harada Nathan , Saeed Mohammed , Singh Satinder , Syed Zeeshan
Published: March 2022

Background:
Postoperative atrial fibrillation (PAF) is a frequent complication following cardiothoracic surgery and is associated with increased length of stay and increased morbidity. This study develops a novel multi-factorial computational model to predict PAF, as well as a simplified risk score for PAF based on this model.

Methods:
A multi-factorial computational model to predict PAF was trained on 592 patients in the MIMIC II database undergoing cardiothoracic surgery at the Beth Israel Deaconess Medical Center, using demographic, comorbidity, laboratory, and echocardiographic parameters. Parameters were chosen using LR stepwise-backward elimination applied to routinely collected covariates via logistic regression. A simplified risk score was created using the retained covariates based on the observed odds ratios (OR). Discrimination for both the model and risk score were calculated using the area under the receiver operating characteristic curve (AUC) via leave one out cross validation.

Results:
The multi-factorial computational model retained the following parameters: age in years (OR 1.06; p<0.001), serum chloride in mEq/L (OR 0.92; p=0.019), and left atrial diameter categorized from 0-3 (OR 1.84; p<0.001). The model achieved a significantly higher level of discrimination relative to any covariate alone (AUC 0.72; p<0.001 relative to all individual covariates). The simplified risk score is calculated as: +2 for age > 67, +1 for serum chloride < 105, +1 for each categorical increase in left atrial diameter (>40mm, >47.5mm, >52.5mm); and achieved comparable performance to the multi-factorial computational model (AUC 0.71; p<0.001) with a graded increase in risk (Figure).

Conclusions:
Multi-factorial computational modeling may provide a robust basis for discriminating between patients at high or low risk of PAF following cardiothoracic surgery. This model can be delivered as a simplified multi-factorial risk score for broad use by the bedside.
Abstract 18193: Transcatheter Aortic Valve Replacement versus Surgical Aortic Valve Replacement in Patients With Cirrhosis: A Propensity Score Matched Analysis
Authors: Thakkar Badal , Patel Aashay , Bhimani Ronak , Patel Nileshkumar J , Bhatt Parth , Savani Chirag , Patel Achint , Patel Samir , Sonani Rajesh , Solanki Shantanu , Arora Shilpkumar , Patel Nilay , Lahewala Sopan , Dave Abhishek , Chothani Ankit , Panaich Sidakpal S , Singh Vikas , Deshmukh Abhishek , Badheka Apurva O
Published: March 2022

Introduction:
Over the past decade, Transcatheter Aortic Valve Replacement (TAVR) has emerged as a therapeutic option for treating severe aortic stenosis in high-risk patients. Patients with liver cirrhosis are at high risk for operative morbidity and mortality when they undergo cardiac surgery. In the present study, in-hospital outcomes are compared in cirrhotic patients undergoing TAVR vs. Surgical Aortic Valve Replacement (SAVR).

Methods:
The study population was derived from the National Inpatient Sample (NIS) for the years 2011 and 2012 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes 35.21 and 35.22 for SAVR, and 35.05 and 35.06 for TAVR. Patients<50 years of age and those with concomitantly other valvular procedures were excluded. ICD-9-CM diagnosis codes were used to identify patients with liver cirrhosis including those with other manifestations of cirrhosis such as portal hypertension and esophageal varices. Using propensity score matching, two matched cohorts were derived in which the outcomes were compared using chi-square test, fisher’s exact test, and student’s t-test.

Results:
There were 30 cirrhotic patients in the SAVR and TAVR group each after propensity score matching. Compared to the TAVR group, the patients in the SAVR group had higher mean cost of hospitalization ($79,263 vs. $63,913, p=0.12), mean post-procedural length of stay (14.3 days vs. 6.2 days, p<0.01), any complications rate (80.0% vs. 60.0%, p=0.09), rate of transfusion of blood or blood products (56.7% vs. 30.0%, p=0.037) and liver complications rate (20.0% vs. 10.0%, p=0.4). The in-hospital mortality rate was same in both the groups (6.7%).

Conclusions:
In high-risk cirrhotic patients, TAVR is a viable option for aortic valve replacement compared to SAVR.
Abstract 18244: Macrophages Infiltrate the Heart With Activation of Adaptive Immunity During Compensated Pressure Overload Hypertrophy
Authors: Patel Bindiya , Ismahil Mohamed A , Bansal Shyam S , Michaud Amy , Prabhu Sumanth D
Published: March 2022

As opposed to chronic ischemic heart failure (HF), spleen-derived macrophages (Mf) are not prominent disease mediators during the chronic stages of pressure-overload (PO) HF. Increases in Mf during the early stages of PO, however, may serve as important drivers of both remodeling and activation of T-cell responses during later stages. Additionally, recent evidence indicates distinct groups of resident and circulating monocyte-derived infiltrating Mf that have different reparative vis-à-vis pro-inflammatory capacities. We
hypothesized
that cardiac Mf are expanded during the early stages of PO, primarily due to an increase in infiltrating Mf, and contribute to long-term T-cell activation in the PO heart. Cardiac Mf were characterized by flow cytometry as MerTK
+
CD64
+
F480
+
MHCII
+
cells, with infiltrating Mf populations identified as expressing chemokine receptor 2 (CCR2). One week after transverse aortic constriction (TAC), C57Bl/6 mice exhibited significant (p < 0.05) hypertrophy (heart weight/body weight 7.7 ± 0.5 vs 5.7 ± 0.2 mg/g; LV wall thickness 0.84 ± 0.03 vs 0.74 ± 0.02), without change in LVEF as compared with sham. There were robust increases in cardiac macrophages (3.15 ± 0.64 vs 1.09 ± 0.24%), specifically in the infiltrating CCR2
+
MHCII
hi
population (1.6 ± 0.5 vs 0.5 ± 0.1%). TAC mice also exhibited higher circulating Gr1
–
CD11b
+
Ly6C
hi
monocytes (2.6 ± 0.5 vs 1.3 ± 0.2%) that are recruited to tissue via CCR2. To determine activation of the adaptive immune response, we analyzed the mediastinal heart draining lymph nodes (MLN) for T-cells and antigen presenting cells. As compared with sham mice, the MLN of TAC mice were larger with greater cellularity (10.8 x 10
5
vs 4.2 x 10
5
), especially related to MerTK
+
CD169
+
Mf and CD3
+
CD8
+
T cells. We conclude that there is both an organ-specific and systemic immune response during compensatory PO hypertrophy, despite the absence of ischemic tissue injury. As infiltrating Mf are known to be less reparative, potently pro-inflammatory, and robust activators of adaptive immune cells, specifically targeting Ly6C
hi
monocyte recruitment and CCR2
+
infiltrating Mf during the early compensated stages of pressure-overload may prevent subsequent inflammatory activation, adverse remodeling, and the transition to HF.
Abstract 18300: Association Between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary and Aorta Provides Insights Into the Pathophysiology of Atherosclerosis
Authors: SALFATI Elias L , Herrington David M , Assimes Themistocles L
Published: March 2022

Autopsy studies suggest that the fatty streak is the earliest identifiable lesion of atherosclerosis. However, not all fatty streaks progress to more advanced lesions of atherosclerosis. Furthermore, the correlation between the extent of fatty streaks in younger persons and the extent of more advanced lesions in older persons as well as the community rates of CAD is substantially lower for the aorta compared to the coronaries. These observations suggest that the pathophysiologic processes leading to the formation of fatty streaks and raised atherosclerotic lesions may differ between the two vascular beds. To test this hypothesis, we analyzed genetic data from 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study between the age of 15 and 34 at the time of accidental death. We ranked subjects by the percent surface area of involvement of fatty streaks and raised lesions in their right coronary artery, thoracic aorta, and abdominal aorta, respectively, on post-mortem examination. We then defined cases within each lesion type and artery location as subjects with a sex specific ranking that was in the top quartile. We found a genetic risk score (GRS) composed of high-risk alleles at 32 loci for clinical CAD operating independent of traditional risk factors to be robustly associated with the probability of being a case for both fatty streaks and raised atherosclerotic lesions in the right coronary artery (Table). In contrast, the same GRS exhibited no association with case status for fatty streaks in the aorta and only a weak trend for association with case status for raised lesions in the aorta. Our findings support the notion that not all fatty streaks are equivalent in their predisposition to atherosclerosis and suggest that some atherosclerosis susceptibility loci uncovered through GWAS studies of clinical CAD may only be active in the coronary tree.
Abstract 18301: Intra-operative Left Coronary Doppler Profile Independently Predicts Need for Ecmo or Late Revision After Arterial Switch
Authors: Halvorsen Fredrik H , Yim Deane , Nield Lynne , Caldarone Christopher A , Van Arsdell Glen S , Pham-Hung Eric , Duong An , Gritti Michael , Hickey Edward J
Published: March 2022

Objective:
We hypothesized that intraoperative coronary Doppler profiles after button implantation would help predict survival and morbidity after arterial switch.

Methods:
Children (N=319) undergoing arterial switch (2000-2012; TGA 190, TGA-VSD 95, TGA-VSD-PS 10, Taussig-Bing 14, others 10) underwent intraoperative echocardiographic assessment of coronary buttons. Studies were blindly reviewed to delineate Doppler gradient, peak flow velocity, velocity-time integral (VTI) and late diastolic flow reversal, which were explored as predictors of death, ICU morbidity and need for late coronary revision via parametric risk-adjusted regression and bootstrap reliability.

Results:
Outcomes included: death=9 (3%), ECMO=13 (4%), surgical coronary revision=9 (3%). Higher left button Doppler values were predictors of chest open duration, post-op JET, need for revision or ECMO. Mean left button gradient was the most reliable - table. Right button Doppler values were not strong predictors of morbidity.

Higher left Doppler gradients confer disproportionate impact - figure. Mean gradient ≥ 1.5 had late revision risk 27%, versus 1.6% for < 1.5 (
P
=.0016).

Intraoperative strategies to improve button geometry included release of fascia (16, 5%) or button revision (9, 3%). Such strategies reduced gradients, velocities and VTI (
P
between .004 and .03
).
Left Doppler values retained their predictive value even in 296 (93%) children who had no such coronary manipulation - table.

Conclusions:
Aiming for mean left coronary gradient < 1.5-2 and peak <4 mmHg through routine Doppler assessment will help lower risk of ECMO and late coronary problems.