bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17122: Human iPS Cell-derived 3D Engineered Cardiac Tissue Including Cardiomyocytes and Multiple Vascular Lineages for Cardiac Regeneration
Authors: Masumoto Hidetoshi , Nakane Takeichiro , Tinney Joseph P , Yuan Fangping , Ye Fei , Kowalski William J , Sakata Ryuzo , Yamashita Jun K , Keller Bradley B
Published: March 2022

Background:
Three-dimensional (3D) engineered cardiac tissues (ECTs) are a robust platform technology to investigate cardiovascular (CV) cell function and provide an excellent microenvironment for tissue implantation and cardiac repair. We generated 3D ECTs using cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) efficiently differentiated from human iPS cells (hiPSCs).

Methods & Results:
We employed 3 different monolayer culture-based differentiation protocols: 1) CM+EC protocol: mesoderm induction followed by VEGF (mes+VEGF) produced a distribution of 61.8±8.0% cTnT
+
-CMs, 19.4±9.1% VE-cadherin
+
-ECs, and 1.7±2.0% PDGFRβ
+
-MCs, (n=26, day15); 2) CM+MC protocol: mes+Dkk1 to induce CMs and MCs; and 3) MC protocol: exclusive induction of MCs. We collected the cells on differentiation day 15 and mixed them to generate 3 classes of ECTs composed of different CV cell population patterns: 1). CM+EC; 2). CM+MC, and 3). CM+EC+MC. We seeded the each cell mixture in a collagen/Matrigel mixture to form spontaneously beating ECTs.
In vitro
force measurement analysis showed that CM+EC+MC ECTs possessed the highest maximum capture rate (4.6±0.6 Hz, P<0.0001) and lowest excitation threshold (1.2±0.3 V/cm, P<0.01) indicating that incorporation of vascular cells augmented tissue maturation and function. We confirmed more preferential alignment of CMs to the ECT long axis in ECTs with MCs. Transmission electron microscopy revealed that incorporation of MCs increased CM sarcomeric structure. Incorporation of both ECs and MCs led to vasculature formation within ECTs during 14 days of
in vitro
culture. These results indicate that incorporation of vascular cells accelerated tissue structural maturation. Next CM+EC+MC ECTs were implanted onto infarcted athymic rat hearts. Echocardiogram revealed a significantly higher cardiac output at 4 weeks after implantation compared to that of sham-operated rats (137±23 vs 95±23 mL/min, P<0.05). Immunostaining 4 weeks after implantation showed epicardial engraftment of human cells as a regenerated myocardium vascularized both by graft and host-derived vasculature.

Conclusion:
HiPSC-derived ECTs including vascular cells showed novel properties relevant for clinical translation.
Abstract 17145: Non-invasive Tracking of Endogenous Bone Marrow Cell Recruitment After Myocardial Infarction in Mice
Authors: Thackeray James T , Korf-Klingebiel Mortimer , Wang Yong , Kustikova Olga S , Bankstahl Jens P , Wollert Kai C , Bengel Frank M
Published: March 2022

Limited clinical benefit of exogenous stem cell therapy has renewed interest in strategies to enhance endogenous cell recruitment after myocardial infarction (MI). Nuclear imaging of stem cell trafficking has been restricted to exogenous stem cells, and may be compromised by low cell retention and continuous expression of reporter genes. We evaluated the feasibility of transplanting reporter gene-labeled endogenous bone marrow under an inducible promoter as a platform for imaging endogenous cell recruitment in MI. Sodium iodide symporter (NIS) was cloned into a lentiviral vector under constitutive (c-NIS) or doxycycline-inducible (i-NIS) promoter. Hematopoetic stem cells (HSCs) were transduced with c-NIS, i-NIS, or a null lentivirus. C57Bl/6 mice (n=57) underwent bone marrow ablation by irradiation and bone marrow was replaced with transduced HSCs (5x105). After 8 weeks, mice underwent coronary artery ligation. Doxycycline (dox) was provided to a subset of i-NIS mice 4d before surgery. Serial SPECT imaging demonstrated increased radioiodine uptake in the perfusion defect of c-NIS compared to NIS-null mice (TBR infarct: MI+3d, 3.0±0.3 v 1.6±0.1 p<0.001; MI+7d, 3.1±0.9 v 1.4±0.3 p<0.01), and comparable uptake in i-NIS transplanted mice. Infarct-to-remote-myocardium radioiodine uptake ratio was 6.5±0.2% higher in c-NIS versus NIS null (p<0.05). Dox-induced i-NIS mice exhibited increased radioiodine uptake in whole myocardium compared to non-induced i-NIS at 1d post-MI (TBR: 2.0±0.3 v 1.6±0.3, p=0.04). This difference dissipated at 7d (TBR 1.5±0.5 v 1.3±0.1, p=0.27). Multi-isotope autoradiography confirmed the presence of radioiodine within the infarct region, associated with histologic markers of inflammation. Bone marrow transplant with NIS reporter gene-labeled HSCs enabled tracking of cell homing post-MI. The inducible construct has the advantage for delivery and/or monitoring of a therapeutic agent with exquisite temporal control.
Abstract 17160: Atrial Fibrosis as a Predictor for Atrial Fibrillation Ablation Success: 5 Years Follow up Study
Authors: Gal Pim , Kaur Gagandeep , Johnson Kara A , Suksaranjit Promporn , Elvan Arif , Pacchia Christina F , marrouche Nassir F
Published: March 2022

Background:
Left atrial (LA) fibrosis assessed by delayed enhancement (DE)-MRI has been shown in multiple studies to be strongly associated with AF and AF treatment outcome. In this study we assess the value of atrial fibrosis in predicting treatment success at 5 years follow up.

Methods:
208 consecutive patients (Mean age 63.0 ±12.2 years, 54% had paroxysmal AF and mean LA fibrosis score was 16.3 ±11.2%) undergoing PVI between 2006 and 2009 with a DE-MRI of sufficient quality for LA fibrosis assessment were retrospectively analyzed. LA fibrosis was classified into 4 UTAH stages as recently described (I: 0-10%; II: 10-20%; III: 20-30%; IV: >40%). Log-rank, Kruskal-Wallis and cox proportional hazard analyses were performed.

Results:
After a median follow-up of 4.8 years (q1-q3: 0.9-6.1), overall AF free survival was 63% after a mean of 1.4 PVI attempts. Figure 1 depicts the significant difference in arrhythmia recurrences among UTAH stages (I: 28% II: 37%: III: 58% IV: 91%, P<0.001), as displayed in the figure. LA fibrosis was a significant predictor of long-term AF free survival (c-statistic: 0.669, P<0.001). The mean number of PVI attempts was significantly different among UTAH stages (I: 1.29, II: 1.32, III: 1.47, IV: 1.8, P=0.003). In multivariate analysis, CHA2DS2VASc score (OR: 1.302, P=0.014), LA volume (OR: 1.008, P=0.013) and LA fibrosis (OR: 1.037, P<0.001) were independently associated with AF free survival.

Conclusion:
LA fibrosis assessed by DE-MRI is an independent predictor of 5-year AF free survival. Moreover, patients with advanced degree of atrial fibrosis seems to require higher number of repeat ablation procedures to maintain sinus rhythm.
Abstract 17173: Incidence of Cardiovascular Disease in Individuals Affected by Recent Changes in Blood Pressure Treatment Guidelines
Authors: Nayor Matthew , Stevenson Meredith D , Xanthakis Vanessa , Larson Martin G , Vasan Ramachandran S
Published: March 2022

Introduction:
The Eighth Joint National Committee (JNC 8) recently recommended important changes to blood pressure (BP) management. Specifically, JNC 8 endorsed relaxing systolic BP (SBP) targets for adults aged ≥60 years and individuals with diabetes or kidney disease. We compared the incidence of cardiovascular disease (CVD) in individuals whose BP management might be affected by these changes.

Hypothesis:
We hypothesized that individuals with BP and treatment status consistent with more lenient BP targets (representative of JNC 8) would demonstrate higher incidence of CVD, compared to individuals achieving more aggressive targets (representative of JNC 7).

Methods:
We included visits from three examination cycles of the Framingham Offspring Study (11,237 visits, mean age 46 years, 53% women), and assigned participants to one of five categories based on resting BP, treatment status, and recommendations according to JNC 7 and JNC 8 guidelines. Cox proportional hazards regression was used to assess if time to CVD varied by BP category.

Results:
During follow-up (mean 11.0 years), there were 1047 incident CVD events (8.5/1000 person-years). Using the group free of hypertension as referent, we observed the highest incidence of CVD in those with treated SBP 140-149 mm Hg and diastolic BP (DBP) <90 mm Hg (multivariable-adjusted hazard ratio [HR] 3.53, p<0.0001), which was consistent among those aged <60 years (HR 3.51, p=0.0004) and ≥60 years (HR 2.74, p<0.0001),
Table
. Participants with untreated SBP 140-149 mm Hg and DBP <90 mm Hg also had increased CVD risk overall (multivariable-adjusted HR 1.88, p<0.0001), as well as within those aged <60 years (HR 2.25, p=0.0002), but not those ≥60 years (HR 1.28, p=0.81).

Conclusions:
Individuals with SBP 140-149 mm Hg and DBP <90 mm Hg have increased risk of CVD, and the risk is especially high for those on treatment. Although observational, our findings may help to address concerns regarding changes proposed by the JNC 8 guidelines.
Abstract 17176: Prognostic Importance of Defibrillator Appropriate Shocks and Anti Tachycardia Pacing in Mild Heart Failure Patients
Authors: Biton Yitschak , Moss Arthur J , Barsheshet Alon , Kutyifa Valentina , Mcnitt Scott , Zareba Wojciech , Goldenberg Ilan
Published: March 2022

Background:
Previous studies had shown that patients with heart failure (HF) who receive implantable cardioverter-defibrillator (ICD) for primary prevention are at increased risk for mortality if they receive a shock. However, information about the prognostic importance of therapies [both shock and anti-tachycardia pacing (ATP)] delivered for a different ventricular arrhythmia (VA) rate is limited.

Methods:
We evaluated the risk for death among 1790 ICD implanted patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy using a time dependent analysis. Patients were categorized to mutually exclusive groups by either the rate of the treated VA (categorized at 200 bpm) or the type of the therapy and VA rate (ATP or shock both categorized at 200 bpm), the reference group was patients that had no device therapy.

Results:
During a median follow-up time of 4 years 423 patients had appropriate ICD therapy, with 163 receiving therapy for VA< 200 bpm only, and 260 for VA≥200 bpm. ICD therapy for VA≥200 was associated with significant increased mortality (HR=2.27 CI 1.48-3.48, p<.001), while therapy for VA<200 was not different from the no therapy group (HR=1.45 CI=0.86-2.44, p=0.162). Accordingly, in a second model both shocks and ATPs for VA≥200 were associated with increased mortality (HR=2.96 CI 1.91-4.60 p<.001 and HR=2.22 CI 0.96-5.14, p=0.063 respectively), while shocks and ATPs for VA<200 did not differ from the no therapy group (HR=1.43 CI 0.52-3.92 p=0.489 and HR=1.43 CI 0.80-2.56, p=0.232 respectively).

Conclusions:
In mild HF patients, who receive ICD for primary prevention, mortality is associated with the rate of the arrhythmia rather than the device rendered therapy.
Abstract 17178: Adaptive Statistical Iterative Reconstruction V: Impact on Image Quality in Ultra-low-dose Coronary Computed Tomography Angiography
Authors: Benz Dominik C , Gräni Christoph , Hirt-Moch Beatrice , Mikulicic Fran , Vontobel Jan , Fuchs Tobias A , Gaemperli Oliver , Kaufmann Philipp A , Buechel Ronny R
Published: March 2022

Introduction:
To accomplish a further decrease in radiation dose for coronary CT angiography (CCTA), advances in iterative reconstruction (IR) algorithms are necessary. The purpose of the present study was to investigate the impact of a latest generation adaptive statistical IR algorithm (ASiR-V, GE Healthcare) on CCTA signal intensity, noise and image quality (IQ).

Methods:
Sixty-five consecutive patients underwent clinically indicated CCTA using a latest generation 256-slice CT scanner (Revolution CT, GE Healthcare) and an ultra-low-dose CCTA protocol (i.e. a BMI-adapted tube current of 180-310 mA and tube voltage of 80-120 kVp). Datasets from each patient were reconstructed at different levels of ASiR-V (i.e. ASiR-V 0% [= filtered back projection, FBP], 20%, 40%, 60%, 80% and 100%). The signal intensity and noise (i.e. attenuation and its standard deviation [in HU]) were measured in each reconstruction by placing a region of interest in the aortic root as well as the proximal RCA and LMA. Furthermore, IQ was assessed for each coronary segment on a 5-point Likert scale by two blinded readers.

Results:
The ultra-low-dose CCTA protocol resulted in a median radiation dose of 0.49 mSv (IQR 0.40-0.60). Signal intensity in the LMA and RCA slightly but significantly decreased with increasing levels of ASiR-V (Table). Nevertheless, the substantial decrease in image noise resulted in a significant increase in signal-to-noise ratio (SNR) in the RCA and LMA. Correspondingly, IQ significantly increased with higher levels of ASiR-V. Applying ASiR-V at a level of 100% led to a 141-143% increase in SNR and a substantial increase in IQ compared to FBP. Of note, for reconstructions with ASiR-V 100%, a significant increase in IQ was even observed when compared to ASiR-V 80%.

Conclusions:
Increasing ASiR-V levels offer substantial image noise reduction and improved IQ for CCTA datasets acquired at low tube voltage and current, enabling application of ultra-low-dose CCTA protocols.
Abstract 17186: Regional Extracellular Volume Fraction Can Identify Cardiac Muscle Changes in Patients With Duchenne Muscular Dystrophy
Authors: Olivieri Laura , Kellman Peter , Cross Russell , Ratnayaka Kanishka , Arai Andrew E , Hansen Michael S , Spurney Chris
Published: March 2022

Background:
Duchenne muscular dystrophy (DMD) is an X-linked inherited disorder causing dilated cardiomyopathy with variable onset and progression. Our aim was to compare native T1 mapping and extracellular volume fraction (ECV) in boys with DMD to controls to identify markers of preclinical myocardial disease.

Methods:
With IRB approval and informed consent/assent, 17 boys with DMD had cardiac magnetic resonance imaging (MRI) with contrast. Ejection fraction (EF), presence of late gadolinium enhancement (LGE), native T1, and ECV mapping were obtained using a modified Look-Locker sequence on a 1.5T MR scanner (Figure 1). Results were compared with age and gender matched controls with no history predisposing to cardiac fibrosis (i.e. bypass, myocarditis, etc).

Results:
Seventeen DMD subjects (age 14 ± 5 years; EF 56% ± 8%) were compared with 13 normal controls (age 17 ± 4 years) with normal EF and no LGE. DMD subjects had low-normal EF (average EF 56% ± 8%) and 10 of 17 (59%) had evidence of LGE, all in the lateral location. Comparing native T1 in DMD vs controls, septal native T1 was 1060 ± 71 ms versus 990 ± 34 ms (p < 0.01) and lateral native T1 was 1090 ± 93 versus 978 ± 37 ms, respectively (p < 0.01). Comparing ECV values in DMD vs controls, septal ECV was 29.6 ± 7.8 and 25.9 ± 3.4 (p = 0.03) and lateral ECV was 32.7 ± 8.7 and 24.4 ±3.6 (p < 0.01), respectively. All DMD patients with abnormal EF and/or presence of LGE also had higher ECV values.

Conclusions:
ECV is strongly-related to DMD and differs significantly compared to normals, particularly in the lateral wall. ECV mapping may be a useful technique for identifying preclinical myocardial changes in DMD.

Figure 1. A) Precontrast T1 map, B) post contrast T1 map and C) ECV map with scale on the right in the short axis projection of a boy with Duchenne muscular dystrophy. Arrows indicate elevated values laterally.
Abstract 17200: Blood Alcohol in Victims of Sudden Cardiac Death in Northern Finland
Authors: Perkiomaki Juha , Hookana Eeva , Kaikkonen Kari , Junttila Juhani , Kortelainen Marja-Leena , Huikuri Heikki
Published: March 2022

Background:
Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. However, data on the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event are limited.

Methods:
Victims of unexpected SCD (n=2,363, age 61±12 years, males 1,940 (82%)) included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico-legal autopsy and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients, who were admitted to a hospital due to an acute myocardial infarction (AMI) (n=128, age 63±10 years, males 100 (78%)) served as controls.

Results:
Based on autopsy findings, 1,691 of these victims had ischemic heart disease and were included in the present analysis. A total of 646 (38%) SCD victims with ischemic heart disease had a blood ethanol concentration above 0‰. Of these victims with blood alcohol test positive, 41% (n=264) had blood ethanol concentration ≥ 1.5‰ and 56% (n=362) ≥ 1‰. Male SCD victims had more frequently alcohol in blood than the females (40% vs. 27%, p<0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n=88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing.

Conclusion:
Almost 4/10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the Northern Finland autopsy population.
Abstract 17206: Osteopontin Levels in Patients at High Cardiovascular Risk
Authors: Pesau Gerfried , Obendorf Florian , Herz Carsten Thilo , Hoebaus Clemens , Koppensteiner Renate , Schernthaner Gerit
Published: March 2022

Introduction:
Proteins which are involved in the bone metabolism have recently been discovered to have significant implications in the development of vascular disease and complications. Osteopontin (OPN) has been suggested as a biomarker of atherosclerosis and vascular calcification.

Hypothesis:
OPN levels may be used for risk stratification in patients with peripheral artery disease (PAD).

Methods:
361 patients suffering from PAD were studied and followed-up for five years. 60 outcome events, defined as death, non-fatal myocardial infarction or non-fatal stroke, were observed. Multiplex bead array technology was used to measure serum levels of OPN at baseline. For basic analysis, the patients were divided into quartiles according to OPN levels. A Cox regression model was used to identify confounding variables.

Results:
A significantly different event-free survival could be observed between all groups (log-rank: p=0.049). When comparing the highest quartile to the rest of the cohort, a further increase in significance could be observed (log-rank: p=0.017). A cut-off point accommodating the most favorable sensitivity (50.0%) and specificity (66.4%) was determined for regression analysis. The hazard ratio was 2.13 (1.26-3.60) in the unadjusted model and reached 2.16 (1.21-3.84) after adjustment for age, gender, diabetes, low-density lipoprotein cholesterol, blood pressure, smoking, c-reactive protein and renal function.

Conclusions:
Our results suggest an association between OPN levels and the rate of cardiovascular events in high risk patients. In our observations this relation was independent of established risk factors.
Abstract 17231: Contact-Mediated Interaction Between Pulmonary Artery Endothelial and Smooth Muscle Cells Promotes a BMPR2-β-catenin-Notch1 Signal Causing Hyperpolarization of Endothelial Mitochondria and a Stalk Cell-like Phenotype
Authors: Miyagawa Kazuya , Li Caiyun G , Hennigs Jan K , Taylor Shalina , Moonen Jan-Renier , Sa Silin , Wang Lingli , Cao Aiqin , Rabinovitch Marlene
Published: March 2022

Background:
Pulmonary arterial hypertension (PAH) is characterized by endothelial (EC) apoptosis related to loss of distal (D) pulmonary arteries (PA) and abnormal proliferation of smooth muscle-like cells (SMC). These features are mediated by impaired cell metabolism. We observed mitochondrial dysfunction in human PAEC with reduced or mutant BMPR2, the gene associated with familial PAH. Deletion of BMPR2 in murine EC causes failure to regenerate DPA and to recover from hypoxia induced pulmonary hypertension. Loss of BMPR2 in PASMC results in mitochondrial dysfunction associated with enhanced proliferation. Since metabolites and other factors are often transferred by cell contact, we investigated how PASMC-PAEC contact impacts PAEC mitochondrial and cellular function, and could be perturbed by a BMPR2 mutation in PAEC and/or PASMC.

Methods and Results:
We used a co-culture system in which PAEC and PASMC from lungs of donor control (c-) or PAH patients with a BMPR2 mutation (m-) were either seeded on opposite sides of a 1μm pore insert or separated to assess non-contact mediated responses. When c-PAEC contacted c-PASMC, PAEC mitochondrial membrane potential (Δψ) increased 6-fold compared to mono-cultured or non-contact co-cultured cells (p < 0.001). These PAEC exhibited a significant increase in proliferation (3-fold increase by Ki-67 staining, p<0.01) and survival (73% reduction in caspase activity, p < 0.001); however we observed a decrease in migration and angiogenic capacity in modified Boyden chamber and matrigel assays (52% and 60% reduction, p < 0.001, respectively). We related the increase in Δψ and the above ‘stalk cell-like’ phenotype to an increase in Notch1 intracellular domain (2.5-fold increase, p < 0.001), as they were abrogated by the gamma secretase inhibitor, and enhanced by the co-transcriptional activator β-catenin (4-fold increase, p < 0.001). When m-PAEC and m-PASMC were used in contact cultures, these features were not observed.

Conclusions:
PASMC in contact with PAEC increase Δψ and produce a Notch and β-catenin mediated stalk cell-like EC phenotype. These features are lost when BMPR2 is deficient in both PAEC and PASMC suggesting that BMPR2-mediated PASMC-EC contact allows PAEC to survive and regenerate in response to damage.
Abstract 17236: Intracranial Hemorrhage in Patients With Atrial Fibrillation in the ARISTOTLE Trial: Clinical Characteristics and Associated Outcomes
Authors: Lopes Renato D , Kolls Bradley J , Guimaraes Patricia O , Wojdyla Daniel M , Hanna Michael , Easton J. Donald , Thomas Laine , Wallentin Lars , Al-Khatib Sana M , Held Claes , Alexander John H , Granger Christopher B , Diener Hans-Christoph
Published: March 2022

Background:
Intracranial hemorrhage (ICH) is associated with poor outcomes in patients with atrial fibrillation (AF) treated with oral anticoagulation. Little is known about clinical characteristics and factors associated with ICH and subsequent outcomes in patients receiving apixaban.

Methods:
The ARISTOTLE trial randomized 18,201 patients with AF and risk of stroke to warfarin or apixaban. All ICH events were identified and adjudicated by a central committee blinded to the study treatment assignment. ICH events were analyzed in patients receiving at least one dose of study drug (N=18,140). Multivariable cox regression models were developed to identify factors associated with ICH.

Results:
There were 174 (1.0%) ICH events. Of those, 111 (67.7%) were intracerebral hemorrhage, 50 (30.7%) subdural hematomas, and 25 (15.3%) subarachnoid hemorrhage. Patients with ICH were older and had higher CHADS
2
score than patients without ICH. Computed tomography was used in 95.2% of patients for the diagnosis of ICH. The majority of ICH cases were spontaneous (71.7%) and 91.4% of patients with ICH presented with some type of neurological deficit. Most (72%) of the patients received conservative treatment and 21% underwent surgical intervention; 71 (40.8%) patients died in hospital. The mean modified Rankin score at discharge of survivors was ≥4 in 23 (22%) patients. Apixaban was superior to warfarin in causing less ICH, including as categorized by each ICH location. Factors associated with ICH were older age, warfarin randomized treatment assignment, prior stroke, geographic region of the world, and use of aspirin at randomization (Table).

Conclusion:
ICH is uncommon in patients with AF who are treated with oral anticoagulant and is associated with very high mortality. Apixaban is superior to warfarin in causing less ICH, irrespective of the location and other risk factors for ICH.
Abstract 17241: Conversion of Recurrent Arrhythmia by the Wearable Cardioverter-defibrillator
Authors: Ringquist Steven , Bianco Nicole R , Szymkiewicz Steven J
Published: March 2022

Background:
Sudden cardiac arrest (SCA) due to ventricular tachycardia (VT) or fibrillation (VF) reportedly reoccurs after an initial successful defibrillation in 60% or more of patients (pts). First responder programs have been associated with 25-71% return of spontaneous circulation (ROSC) and 73% survival to hospital admission when pts require additional, more than one, defibrillation treatment shock. Although VT/VF SCA occurring in wearable cardioverter defibrillator (WCD) pts has a 98% first shock success and 94% survival, the incidence and outcomes of recurrent VT/VF after an initial, successful shock is unknown.

Methods:
The ZOLL registry of WCD pts was used to identify 1,219 USA pts appropriately treated from Oct 2009 through Aug 2014. Pts were included if they met the following: Group A, 1 shock in response to a detection cycle triggered by a single VT/VF episode; Group B, 1 shock in response to the first of two consecutive detection cycles, and 1 or more appropriate shocks delivered in response to a second, recurring VT/VF episode.

Results:
There were 1,145 pts successfully converted with the first shock to VT/VF. Of these, 846 (74%) did not have VT/VF recurrence (Group A), while 299 (26%) were defibrillated again for recurrent VT/VF (Group B), with a median time between treatments of 71 minutes. Demographic and clinical characteristics of Group A and Group B differed only in the frequency of implantable cardioverter defibrillator explant pts (p<.01), which was increased 2-fold in Group B. First shock efficacy among Group A was high with 97% conversion success and 92% acute survival observed. Among Group B pts the recurring VT/VF shock conversion (97%) and acute survival (92%) was not significantly different, and conversion success was independent of the elapsed time between episodes. Deaths in Group B were primarily associated with a shorter elapsed time (10 minutes or less) between new VT/VF episodes (Pearson’s correlation 0.99).

Conclusions:
A smaller fraction of WCD pts (26%) experience recurrent VT/VF than reported during first responder resuscitation. Conversion success of recurrent VT/VF among WCD pts was 97% and independent of the elapsed time between VT/VF episodes. SCA survival regardless of VT/VF recurrence was high, 92%.
Abstract 17242: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Cardiac Allograft Vasculopathy
Authors: Lazarte Julieta , Goldraich Livia , Manlhiot Cedric , Kawajiri Hiroyuki , Grosman-Rimon Liza , Ghashghai Arash , Rao Vivek , Delgado Diego
Published: March 2022

Introduction:
Human Leukocyte Antigen (HLA)-G is an immune inhibitor molecule that has been shown to inhibit smooth muscle cell proliferation in vitro and promote vasculature protection against cardiac allograft vasculopathy (CAV). Single polymorphism nucleotides (SNPs) throughout the gene influence the expression of HLA-G. The association between HLA-G SNPs in heart transplant recipients or donors and CAV remains unclear. Objective: To determine the association between HLA-G SNPs from recipient and donor and severe CAV post heart transplant.

Methods:
Retrospective cohort in which 251 adult heart transplant recipients and 196 matching donors were evaluated for various HLA-G SNPs. The recipients were screened for CAV according to institutional protocol. Coronary angiographies were graded according to the International Society for Heart and Lung Transplantation classification and severe CAV was defined as 2/3 categories. DNA was genotyped for SNPs 5’ URR 201, 3’ UTR 3196, 3187, 3142 and 14bp INDEL using the Sequenom MassARRAY Platform. The association of genotypes and diagnosis of severe CAV were evaluated in parametric hazard regression model.

Results:
General characteristics: recipient age 48±12 years, 69% males and donor age 35±14 years. Over a median follow-up of 6 years, 20 (8%) recipients were diagnosed with severe CAV. In multivariable analysis adjusting for donor age, donor cause of death and pre-transplant creatinine, the presence of donor SNP 201 (CC vs TT/TC) was associated with increased risk for severe CAV (HR 5.29; CI 1.70-16.20; p= 0.004), as well as donor SNP 3142 (GG vs CG/CC) was associated (HR 10.05; CI 1.40-71.65; p< 0.02). Furthermore, matching between recipient and donor genotypes at SNP 201 was also associated with increased risk (HR 7.50; CI 2.50-22.39; p< 0.001).

Conclusions:
Donor HLA-G SNPs 3142/201 and recipient/donor genotype matching for SNP 201 were independent risk factors for the diagnosis of severe CAV. This is the first investigation to identify an association between the HLA-G SNPs mentioned and CAV diagnosis. This association suggests that differences in HLA-G polymorphisms constitute a pathogenic pathway to be explored for potential enhancement of diagnostic, preventive and therapeutic strategies for CAV.
Abstract 17252: High Low-density Lipoprotein Cholesterol Levels are Common Among High-risk Patients One Year After Initiating Statin Therapy: Results of a Large Canadian Cohort Study
Authors: Mitchell Dominic , Habib Mohdhar , Pericleous Louisa , Petrella Robert J
Published: March 2022

Introduction:
Dyslipidemia is an important modifiable risk factor for CVD, yet studies show that dyslipidemia is undertreated in Canada. To evaluate the management of dyslipidemia in patients at high risk for CVD (including heterozygous familial hypercholesterolemia [HeFH] and statin intolerant [SI]), we assessed lipid lowering treatment patterns, LDL-C target achievement, prevalence of CV risk factors, and the incidence of CV events, in a large Canadian cohort.

Methods:
We retrospectively analysed data from an open cohort of patients initiating statin therapy between 2004 and 2012 using the Southwestern Ontario primary care practice database. Inclusion criteria were diagnosis of dyslipidemia, ≥ 1 statin prescription, and ≥ 2 years statin-free baseline data. Patients were stratified into 3 CV risk levels. Here, we report the results of the high-risk patient group.

Results:
In a cohort of 41 733 patients who initiated statin therapy, we identified 14 607 (35%) high-risk patients. At baseline, the mean (SD) age was 54 (7) years, 51% were male, and LDL-C was 3.07 (0.41) mmol/L. On average, patients had 3 CV risk factors. Age (66% male > 45 y; 90% female > 55 y), obesity (36%, BMI > 27 kg/m
2
), high-risk hypertension (31%), and diabetes (17%) were identified as the most important risk factors. After 1-year follow-up, 25% (n=3652) of patients who initiated statin therapy failed to reach target LDL-C. Among high-risk patients with SI (n=1294), 84% (n=1089) discontinued therapy or had a dose decrease. Six months after SI diagnosis, 51% (n=656) did not meet the LDL-C target; 74% (n=484) of these patients had their statin dose decreased or stopped or were treated with a non-statin. In the prevalent cohort (new and follow-up patients in 2012), 52% (n=64) of HeFH patients were treated for secondary prevention (ie, had experienced a prior CV event) and had LDL-C > 2.59 mmol/L, and among high-risk SI patients with LDL-C > 2.59 mmol/L, 65% (n=2304) were diagnosed with coronary heart disease and 32% (n=1132) were treated for secondary prevention.

Conclusions:
Despite widespread statin use, a significant therapeutic need remains for CV high-risk patients who fail to reach the recommended LDL-C target.
Abstract 17262: MicroRNA-23b Mediated Inhibition of Gsk-3β and Nischarin Promotes Proliferation of Cardiomyocytes
Authors: Crocker Jeffrey S , Pandey Raghav , Ahmed Rafeeq P
Published: March 2022

Background:
Promoting proliferation of cardiomyocytes (CMs) following myocardial infarction is a promising approach for cardiac regeneration. Recent studies from our lab identified a panel of microRNAs inducing proliferation of adult CMs; of these miR-23b was one of the most robust CM proliferation-inducing miR and is conserved across species. In silico analysis identified binding sites for miR-23b on the 3’UTRs of both GSK-3β (GSK) and nischarin (NISCH). Here, we hypothesize that miR-23b promotes both in vitro and in vivo proliferation of CMs by regulating the expression of cell cycle inhibitors GSK and NISCH.

Methods and Results:
Adult CMs isolated from 8-12 week old female rats were transfected with hsa-miR-23b, cel-miR-67 (control), siGSK, siNISCH, siGSK + siNISCH (si=siRNA). EdU was added (5 μM) each day post-transfection and cells were fixed on day 6 for IF staining (Troponin-I, EdU, pH3, and DAPI), protein, and RNA analysis. A significant increase in EdU+ CMs was found in cells transfected with miR-23b (8.51%±0.78), siGSK (8.30%±1.31) and siNISCH (5.73%±1.52) when compared to control miR cel-67 (3.13%±0.84). Interestingly, simultaneous inhibition of both GSK and NISCH exhibited robust proliferation (13.88%±1.15) similar to miR-23b transfection. Luciferase assay confirmed binding sites for miR-23b on the 3’UTR of GSK with a 0.85±0.04 fold reduction of chemiluminescent activity. Compared to control, western blotting following miR-23b transfection revealed an increase in pERK (2.46±0.69 fold), a decrease in GSK (0.18±0.12 fold), and an increase in β-catenin (4.17±2.03 fold), indicating miR-23b mediated inhibition of GSK and subsequent increase in β-catenin. For in vivo analysis, 6 day old Fischer rats received intraperitoneal adenoviral miR-23b (10^11 viral particles) followed by EdU injections on alternate days. On day 6, rats were sacrificed, and the hearts were fixed/sectioned for IF staining. Rats injected with miR-23b expressed higher levels of EdU (2.42±0.46 fold), and decreased fold of GSK (0.32±0.10) and NISCH (0.29±0.17) compared to control as confirmed via IHC staining.

Conclusion:
MiR-23b promotes proliferation of CMs by simultaneous inhibition of both GSK and NISCH and upregulation of downstream targets pERK and β-catenin.
Abstract 17295: Effect of Atrial Rate-responsive Pacing in the Incidence of Sustained Atrial Arrhythmias in Patients With Implantable Cardioverter-defibrillators
Authors: Fontenla Adolfo , Lopez-Gil Maria , Martinez-Ferrer Jose B , Rodriguez Anibal , Alzueta Javier , Garcia Enrique , Basterra Nuria , Romero Rafael , Fernandez de la Concha Joaquin , Viñolas Xavier , Villacastin Julian , Salguero Rafael , Arribas Fernando
Published: March 2022

Introduction:
Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence, but there is little data regarding its use in implantable cardioverter-defibrillator (ICD) patients.

Hypothesis:
Atrial RRP may increase the occurrence of sustained atrial arrhythmias when programmed in ICD recipients.

Methods:
Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed by remote monitoring.

Results:
Data from 415 patients was collected after a 21.3±14.1 months follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated to a higher atrial pacing percentage in the overall study population (51.2±33.8% versus 18.4±25.7%, P<0.001) and to a higher ventricular pacing percentage among dual-chamber devices (22.3±37.6% versus 9.3±25%, P 23 hours) were history of AF (odds ratio: 7.98; 95% confidence interval: 4.11-15.47; p<0,001) and atrial RRP (odds ratio: 3,58; 95% confidence interval: 1.82-7.03; p<0,001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with and without a history of AF (Figure). Within patients with a history of AF, atrial RRP was also associated with a higher median of AT/AF episodes/patient (18.5 [interquartile range: 339] versus 8 [69], P=0.016) and a higher percentage of time recording AT/AF (9.21% [36.32] versus 1.18% [16.31], P=0.024). Cumulative incidence of sustained AT/AF episodes > 23 hours was proportional to the atrial pacing percentages.

Conclusions:
Atrial RRP in ICD patients was related to a higher cumulative incidence of sustained atrial arrhythmias >23 hours. This pacing mode seems to have an atrial proarrhythmic effect not described up to now in ICD patients, especially among those with a history of AF.
Abstract 17324: Associations Between Individual Saturated Fatty Acid Intake and Risk of Coronary Heart Disease Among American Men and Women
Authors: Zong Geng , Wanders Anne , Marjan Alssema , Zock Peter , Sun Qi
Published: March 2022

Dietary intervention studies report neutral effects of stearic acid (18:0) on blood lipids, compared with lauric acid (12:0), myristic acid (14:0) and palmitic acid (16:0). Evidence from observational studies on the associations between intakes of individual saturated fatty acids (SFAs) and risk of CHD is scarce.

We prospectively followed 72,102 women in the Nurses’ Health Study (1984-2010) and 42,874 men in the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaire and updated every 4 years.

Baseline percentages of energy from total and major 4 subgroups (4:0-10:0, 12:0-14:0, 16:0, and 18:0) of even-chain SFA, were 11.8%, 0.6%, 1.3%, 6.6%, and 3.3% for women, and 10.8%, 0.5%, 1.1%, 6.1%, and 3.1% for men. Spearman correlations among baseline individual SFA intakes ranged from 0.43 (between 4:0-10:0 group and 18:0 in both cohorts) to 0.92 (between 16:0 and 18:0 in women). We generated 18:0 residual by regressing 18:0 on intakes of other SFAs. During 2.6 million person-years of follow-up, 6,843 incident CHD cases were documented. In the multivariate model, intakes of 4:0-10:0, 12:0-14:0, and 16:0, but not 18:0, were positively associated with risk of CHD (P<0.05). After further adjusting for dietary factors, hazard ratios (95% confidence interval, HR[95%CI]) of CHD per 1% energy increase were 1.10 (0.98, 1.22; P=0.10) for 4:0-10:0, 1.11 (1.03, 1.18; P=0.003) for 12:0-14:0, 1.09 (1.04, 1.13; P<0.001) for 16:0, and 0.98 (0.94, 1.01; P=0.22) for 18:0. The HR per 0.2 increase in the ratio of polyunsaturated fat (PUFA) to SFA was 0.93 (0.90, 0.96; P<0.001). The HRs of CHD risk per 1% of energy PUFA replacing SFA were 0.92(0.85,0.99; P=0.03) for 12:0-14:0 and 0.91(0.87,0.95;P<0.001) for 16:0; but PUFA replacing 4:0-10:0 or 18:0 were not associated with CHD risk: HRs were 0.98(0.86,1.11; P=0.74) and 0.97(0.93,1.01; P=0.19), respectively.

Our findings indicate that while 12:0-16:0 were associated with increased CHD risk, short-to-medium-chain SFA and 18:0 were not. However, our results need to be interpreted with caution because saturated fatty acids share common food sources and are highly correlated.
Abstract 17361: Loss of Notch1 in the Secondary Heart Field Exacerbates Ascending Aortic Aneurysm and Causes Aortic Rupture in Marfan Syndrome Mice
(Best of Basic Science Abstract)
Authors: Koenig Sara N , Rowland Patrick , Trask Aaron J , Lilly Brenda , Garg Vidu
Published: March 2022

Ascending aortic aneurysm (AscAA) is a life-threatening disease that affects approximately 3.5 in 100,000 people per year, but the mechanisms of AscAA remain poorly understood. We previously reported that
NOTCH1
mutations are associated with familial bicuspid aortic valve (BAV), and a subset of these individuals displayed BAV aortopathy. NOTCH1 is expressed in multiple cell lineages that contribute to the aorta, and we found dysregulation of activated NOTCH1 expression in aneurysmal tissue from Marfan syndrome and BAV patients in comparison to control tissue. To investigate the role of NOTCH1 in AscAA,
Notch1
haploinsufficiency was introduced into the Marfan syndrome mouse (

Fbn1
C1039G/+

), a well-described model of AscAA. Serial echocardiographic, gross and histological characterization of the
Notch1
deficient Marfan syndrome mice (

Notch1
+/-
;Fbn
C1039G/+

) demonstrated an exacerbated AscAA phenotype when compared to

Fbn1
C1039G/+

mice. The compound mutant mice had increased aortic root diameter by three months of age (diameter:

Notch1
+/-
;Fbn
C1039G/+

= 2.11±0.11mm and

Fbn1
C1039G/+

= 1.86±0.05mm, p<0.05) as well as a higher rate of dilation from 1-5 months of age (rate:

Notch1
+/-
;Fbn
C1039G/+

=0.24±0.06mm/month and

Fbn1
C1039G/+

=0.09±0.03mm/month, p<0.05).

Notch1
+/-

and wildtype littermate mice had normal aortic diameters. Furthermore, a small subset (4/66) of the compound mutant mice succumbed to ascending aortic rupture, which was not observed in the

Fbn1
C1039G/+

mice (0/63). Although endothelial Notch1 is critical for cardiovascular development, mice with heterozygous loss of
Notch1
in endothelial cells that harbor the
Fbn1
C1039G mutation (

Notch1
flox/+
;Tie2-Cre
+/-
;Fbn1
C1039G/+

) did not recapitulate the phenotype of the

Notch1
+/-
;Fbn
C1039G/+

mice. Surprisingly, the phenotype was recapitulated with heterozygous loss of
Notch1
in the lineage of secondary heart field cells (

Notch1
flox/+
;Mef2C-AHF-Cre
+/-
;Fbn1
C1039G/+

) but not smooth muscle myosin heavy chain-expressing cells (

Notch1
flox/+
;Myh11-Cre
+/-
;Fbn1
C1039G/+

). Our findings support a novel role for Notch1 in the non-endothelial secondary heart field and suggest that this loss of Notch1 alters a developmental process that contributes to AscAA.
Abstract 17376: Novel Non-contrast MRI Technique for Visualization of Ablation Lesions
Authors: Kholmovski Eugene G , Ranjan Ravi , Angel Nathan , Marrouche Nassir
Published: March 2022

Introduction:
Late gadolinium enhanced MRI (LGE-MRI) is widely used to assess RF ablation lesions. However, this technique requires contrast injection and lesion visibility changes with time after injection. Non-contrast T1-weighted (T1w) MRI is only applicable to reliably visualize acute (< 7 days) RF lesions.

Hypothesis:
T2*-weighted MRI can be used to visualize ablation lesions.

Methods:
Novel non-contrast MRI technique for sub-acute (> 7 days) lesion visualization has been developed. This T2*-weighted technique exploits the difference in susceptibility between normal and ablated myocardium. Transformation of hemoglobin from blood vessels damaged during ablation into hemosiderin reduces T2* of ablated tissues. To validate the proposed technique RF ablations were performed in 3 canines using ThermoCool catheter (Biosense Webster) at 30 Watts for 30 seconds. Imaging studies were performed on a 3T MRI scanner (Verio, Siemens) at 0, 1, 4, and 8 weeks post-ablation. Scan protocol included T1w, T2*, and LGE scans with resolution of 1.25x1.25x2.5 mm.

Results:
Representative T1w, T2*, and LGE images are shown in Figure 1. All RF lesions (n=13) were readily detectable on non-contrast T1w images acquired acutely (Fig. 1a). Lesion visibility in T1w was drastically reduced 1 week post-ablation (Fig. 1b). Visibility of the lesions in T2* images improves with time after ablation (Fig. 1c-e). Lesions have hypointense boundaries in T2* images acquired 1 and 4 weeks post-ablation. Whole lesions are hypointense in T2* images acquired 8 weeks post-ablation. Strong correlation (R2=0.9747) between lesions volumes estimated from LGE and T2* acquired 8 weeks post-ablation was found (Fig. 2).

Conclusions:
Non-contrast T2* technique for visualization of RF ablations has been developed and validated. The technique can be used to detect RF lesions as early as a week post-ablation. T2* contrast of the lesions improves with time after ablation as amount of hemosiderin increases.
Abstract 17419: Sex and Race Related Disparities in Care and Outcomes After Hospitalization for Coronary Artery Disease Among Older Adults
Authors: Li Shanshan , Fonarow Gregg C , Mukamal Kenneth , Liang Li , Schulte Phillip J , Smith Eric E , DeVore Adam , Hernandez Adrian F , Peterson Eric D , Bhatt Deepak L
Published: March 2022

Background:
It is unclear to what extent following a standard performance protocol will help reduce gaps in cardiovascular health among sexes, racial/ethnic groups, and geographic regions in United States hospitals.

Method:
Based on the Get With The Guidelines Coronary Artery Disease (GWTG-CAD) registry linked with Medicare inpatient data, we included 49,358 patients, age 65 years or older, from 366 US hospitals from 2003 to 2009. Our primary outcome was 3-year all-cause mortality. Exposures included sex, race/ethnicity, and geographic region. Our mediator was a composite score of quality of care, defined as the total number of performance measures the patient received divided by total number of performance measures the patient was eligible for. Logistic regression with generalized estimating equations and mediation analysis were used.

Results:
During 3 years of follow-up, 16,130 deaths were identified. Compared with men, women were less likely to receive optimal care at discharge (adjusted odds ratio (aOR)=0.92, 95% Confidence Interval (CI): 0.88-0.95, p<0.0001). We identified a significant interaction between sex and quality of care measures (p for interaction=0.04). Compared with men, women had higher odds of mortality (aOR=1.23, 95%CI: 0.99-1.54, p=0.06) if they received sub-optimal care, though the sex disparity disappeared with optimal care (aOR=0.97, 95%CI: 0.92-1.01, p=0.13). There was no difference in terms of quality of care across racial/ethnic groups or geographic regions. Compared with whites, blacks had higher mortality (aOR=1.36, 95%CI: 1.24-1.50, p<0.0001), and the disparity persisted regardless of the quality of care received. We did not identify a significant mortality difference based on geographic region.

Conclusion:
Compared with men, women were less likely to receive optimal care at discharge which was associated with higher mortality. The observed sex disparity in mortality could potentially be reduced or even eliminated by providing equitable and optimal care. In contrast, the higher mortality observed in black patients could not be accounted for by differences in the quality of care measured in this study. We did not observe differences in care or outcomes by geographic region.
Abstract 17434: National Variation in Post-tavr Antithrombotic Therapy Utilization in Patients With Atrial Fibrillation: Insights From the Sts/acc Tvt Registry®
Authors: Sherwood Matthew W , Vemulapalli Sreekanth , Vora Amit N , Dai David D , Halim Sharif , Kiefer Todd L , Hughes G. Charles , Harrison J. Kevin , Peterson Eric D
Published: March 2022

Background:
Oral anticoagulant and antiplatelet medications are routinely prescribed for patients with pre-operative atrial fibrillation (AF) after TAVR, however, there are no data on the optimal treatment strategy, or the patterns of medication use for these patients in the United States.

Methods:
Using the STS/ACC TVT Registry we evaluated patients with atrial fibrillation undergoing TAVR from 2011-2014. Clinical outcomes included death, bleeding, and stroke at 1 year of follow up.

Results:
Of the 10,514 patients in the TVT registry during this time period, 4540 patients (43%) had pre-existing AF. Of these, 52% (n=2348) of patients were discharged with an OAC (2226 on warfarin, 122 on dabigatran) and 48% (n=2192) of patients were discharged without an OAC, with substantial unadjusted hospital level variation (Figure). Patients discharged on OAC had concomitant ASA monotherapy most frequently (1461; 62%), but dual antiplatelet therapy (DAPT)(405; 17%), clopidogrel monotherapy (224; 9.5%), and no additional therapy (258; 11%) were also used. Patients discharged without OAC were most frequently discharged on DAPT (1401; 64%), though monotherapy (680; 31%), and no antiplatelet therapy (111; 5%) were also prescribed. Patients discharged on OAC compared with those not prescribed OAC were similar with respect to age (84 vs. 85 years), gender (50 vs. 49% female), and most comorbid illnesses, but had lower STS PROM risk scores (7.8 vs. 8.7), and were less likely to have renal failure (6.1 vs. 7.0%). Patients with AF undergoing TAVR had 1-year unadjusted rates of death (23.7%; 95% CI 22.3- 25.1%), bleeding (20.2%; 95% CI 18.8-21.6%), and stroke (3.8%; 95% CI 3.2-4.4%).

Conclusions:
Given the substantial variation in the patterns of antithrombotic therapy prescribed for US patients with AF post-TAVR and the 1-year rates of death, stroke, and bleeding observed, sustained effort is needed to determine the optimal antithrombotic medical therapy for these patients.